MedPath

Adding an Immunotherapy Drug, MEDI4736 (Durvalumab), to the Usual Chemotherapy Treatment (Paclitaxel, Cyclophosphamide, and Doxorubicin) for Stage II-III Breast Cancer

Phase 3
Recruiting
Conditions
Anatomic Stage II Breast Cancer AJCC v8
Anatomic Stage III Breast Cancer AJCC v8
HER2-Negative Breast Carcinoma
Hormone Receptor-Positive Breast Carcinoma
Interventions
Other: Genetic Testing
Procedure: Biospecimen Collection
Procedure: Mammography
Other: Quality-of-Life Assessment
Registration Number
NCT06058377
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

This phase III trial compares the addition of an immunotherapy drug (durvalumab) to usual chemotherapy versus usual chemotherapy alone in treating patients with MammaPrint High 2 Risk (MP2) stage II-III hormone receptor positive, HER2 negative breast cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as paclitaxel, doxorubicin, and cyclophosphamide work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. There is some evidence from previous clinical trials that people who have a MammaPrint High 2 Risk result may be more likely to respond to chemotherapy and immunotherapy. Adding durvalumab to usual chemotherapy may be able to prevent the cancer from returning for patients with MP2 stage II-III hormone receptor positive, HER2 negative breast cancer.

Detailed Description

PRIMARY OBJECTIVE:

I. To compare breast cancer event-free survival between participants randomized to standard of care neoadjuvant chemotherapy alone versus standard of care neoadjuvant chemotherapy concurrent with durvalumab.

SECONDARY OBJECTIVES:

I. To compare pathologic complete response rates (ypT0/is, ypN0) in participants randomized to standard of care chemotherapy alone versus (vs.) standard of care neoadjuvant chemotherapy concurrent with durvalumab.

II. To compare residual cancer burden distribution between participants randomized to standard of care neoadjuvant chemotherapy vs. standard of care neoadjuvant chemotherapy concurrent with durvalumab.

III. To compare distant relapse-free survival between participants randomized to standard of care neoadjuvant chemotherapy vs. standard of care neoadjuvant chemotherapy concurrent with durvalumab.

IV. To compare overall survival between participants randomized to standard of care neoadjuvant chemotherapy vs. standard of care neoadjuvant chemotherapy concurrent with durvalumab.

V. To compare the frequency and severity of toxicities between participants randomized to standard of care neoadjuvant chemotherapy vs. standard of care neoadjuvant chemotherapy concurrent with durvalumab among those who initiate the assigned treatment.

PRIMARY QUALITY OF LIFE (QOL) OBJECTIVES:

I. To compare the change in fatigue (Patient Reported Outcomes Measurement Information System \[PROMIS\] Fatigue) experienced by participants randomized to neoadjuvant durvalumab plus chemotherapy vs. participants randomized to chemotherapy alone at completion of active treatment (at 20 weeks from baseline).

II. To compare the change in global physical health (PROMIS Global Health) experienced by participants randomized to neoadjuvant durvalumab plus chemotherapy vs participants randomized to chemotherapy alone at completion of active treatment (at 20 weeks from baseline).

SECONDARY QOL OBJECTIVES:

I. To compare the change in fatigue and global physical health experienced by participants randomized to neoadjuvant durvalumab plus chemotherapy vs participants randomized to chemotherapy alone during treatment (at 12 weeks from baseline).

II. To compare the changes in global physical health and fatigue subsequent to treatment (at years 1 and 2) between the two randomized study arms.

III. To compare the changes in global mental health (PROMIS Global Health) during active treatment (weeks 12, 20) and subsequent to treatment (at years 1 and 2) between the two randomized study arms.

IV. To compare the severity and frequency of treatment-related symptoms using Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) items (diarrhea, nausea, cough, shortness of breath, rash, and musculoskeletal pain) over time experienced by participants receiving neoadjuvant durvalumab plus chemotherapy versus chemotherapy alone.

BANKING OBJECTIVE:

I. To bank specimens for future correlative studies.

OUTLINE:

STEP 1: Patients without a known MP2 score undergo MammaPrint testing on a previously-collected tissue sample. Patients with MP2 score proceed to STEP 2.

STEP 2: Patients are randomized to 1 of 2 arms.

ARM 1: Patients receive paclitaxel intravenously (IV) on days 1 and 8 of each cycle. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM 2: Patients receive paclitaxel IV on days 1 and 8 of each cycle and durvalumab IV over 60 minutes on day 1 of cycles 1, 3, and 5. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle, and durvalumab IV over 60 minutes on day 1 of cycles 7 and 9. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

All patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at standard of care (SOC) surgery and undergo collection of blood samples throughout the study.

After completion of study treatment, patients are followed until death or 10 years, whichever occurs first.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
3680
Inclusion Criteria
  • STEP 1: REGISTRATION (SCREENING): Participants must have histologically confirmed estrogen receptor (ER) positive and/or progesterone receptor (PR) positive (hormone receptor positive) and HER2 negative breast cancer, as per American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines

    • NOTE: Participants with HER2 positive disease by ASCO CAP guidelines are ineligible. HER2 negative and HER2 low or equivocal cases as per ASCO CAP guidelines that do not receive HER2 targeted therapy are eligible
  • STEP 1: REGISTRATION (SCREENING): Participants must have clinical stage II or III breast cancer

    • NOTE: Participants with inflammatory breast cancer are eligible
    • NOTE: Participants with occult (i.e. undetectable) primary breast cancer with axillary nodal involvement are not eligible, as MammaPrint testing has not been validated on tissue obtained from an axillary lymph node
  • STEP 1: REGISTRATION (SCREENING): Participants must not have metastatic disease (i.e., must be clinically M0 or Mx) Systemic staging studies with imaging should follow routine practice as per National Comprehensive Cancer Network (NCCN) and ASCO guidelines

  • STEP 1: REGISTRATION (SCREENING): Participants must not have locally recurrent breast cancer

  • STEP 1: REGISTRATION (SCREENING): Participants with multifocal disease in the same breast or synchronous bilateral primary tumors are eligible, however, all tumors that are biopsied must be hormone receptor positive and HER2 negative per ASCO CAP guidelines and at least one of the tumors must be MammaPrint High-2. MammaPrint can be performed sequentially on biopsies as it is sufficient to have MammaPrint High 2 status on at least one of the lesions

    • NOTE: Biopsy of multiple lesions in the same breast is not required if the clinical presentation is consistent with a single disease process that is multifocal in nature. However, if there is clinical suspicion of two distinct primary breast malignancies, additional biopsies should be pursued
  • STEP 1: REGISTRATION (SCREENING): Participants must have either adequate tissue available to submit on-study or a prior known MammaPrint Index Score that is MP2 status

    • Submitting tissue for on-study MammaPrint testing:

      • Participants must have a minimum of ten, unstained formalin-fixed paraffin-embedded (FFPE) slides (4-5 micron thickness) available from initial tumor biopsy for MammaPrint assessment

        • NOTE: Participants must agree to have this tissue submitted to Agendia for MammaPrint Index Scoring and to have subsequent results disclosed to Southwest Oncology Group (SWOG) Cancer Research Network OR
    • Submitting prior known MammaPrint Index Score:

      • If a MammaPrint Index Score report from within the last 12 weeks is already known and is MP2 status, the participant must be registered to Step 2 immediately following Step 1 registration provided they meet all other criteria. MP2 status is defined as a MammaPrint Index score between negative 1.0 and negative 0.57 (-1.0 to -0.57, including negative 1.0 and negative 0.57) tested from initial tumor biopsy

        • NOTE: Participants must agree to have their commercial MammaPrint Index Score disclosed to SWOG Cancer Research Network
        • NOTE: Participants with prior known MammaPrint result that is not MP2 status should not be enrolled to either step of this study
        • NOTE: Participants enrolling with known MP2 status (i.e. MP already obtained as routine care) must only sign the treatment informed consent form. Screening consent is not required when MP2 status is known prior to study enrollment
  • STEP 1: REGISTRATION (SCREENING): Participants must not have received any prior treatment for their current breast cancer, including chemotherapy, immunotherapy, biologic or hormonal therapy, and must be candidates for doxorubicin, paclitaxel, and durvalumab therapy

  • STEP 1: REGISTRATION (SCREENING): Participants must be >= 18 years old at the time of registration

  • STEP 1: REGISTRATION (SCREENING): Participants must have body weight > 30 kg

  • STEP 1: REGISTRATION (SCREENING): Participants must have Zubrod Performance Status of 0-2

  • STEP 1: REGISTRATION (SCREENING): Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

  • STEP 1: REGISTRATION (SCREENING): Participant must not have medical contraindications to receiving immunotherapy, including history of non-infectious pneumonitis that required steroids or active autoimmune disease that has required systemic treatment with disease modifying agents, corticosteroids or immunosuppressive drugs in the past two years. Replacement therapy (e.g. thyroxine for pre-existing hypothyroidism, insulin for type I diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Intra-articular steroid injections are allowed

  • STEP 1: REGISTRATION (SCREENING): NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

    • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
    • For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
  • STEP 2: RANDOMIZATION: Participants must have met all eligibility criteria for Step 1 Registration

  • STEP 2: RANDOMIZATION: Participants must have MammaPrint High Risk 2 result

    • For participants submitting tissue for on-study MammaPrint testing:

      • Participants must be registered to Step 2: Randomization within 84 calendar days (12 weeks) after receiving an MP2 status from the MammaPrint Index score. MP2 status is defined as a MammaPrint Index score between negative 1.0 and negative 0.57 (-1.0 to -0.57, including negative 1.0 and negative 0.57) from initial tumor biopsy OR
    • Submitting commercial MammaPrint Index Score:

      • If a MammaPrint Index Score report from within the last 12 weeks is already known and is MP2 status, the participant must be registered to Step 2 immediately following Step 1 registration provided they meet all other criteria. MP2 status is defined as a MammaPrint Index score between negative 1.0 and negative 0.57 (-1.0 to -0.57, including negative 1.0 and negative 0.57) tested from initial tumor biopsy

        • NOTE: Participants without a MammaPrint High-Risk 2 score must not be registered to Step 2 Randomization
  • STEP 2: RANDOMIZATION: Participants must not have received live vaccines within 28 days prior to study Step 2: Randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Seasonal influenza vaccines and coronavirus disease 2019 (COVID-19) vaccines are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated vaccines, and are not allowed

  • STEP 2: RANDOMIZATION: Participants must not be planning to receive any concurrent non-protocol directed chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment while receiving treatment on this study

  • STEP 2: RANDOMIZATION: Participant must have Zubrod Performance Status of 0-2

  • STEP 2: RANDOMIZATION: Participants must not have a history of (non-infectious) pneumonitis that required steroids or evidence of active pneumonitis within two years prior to Step 2: Randomization

  • STEP 2: RANDOMIZATION: Participants must not have active autoimmune disease that has required systemic treatment in the past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) prior to Step 2: Randomization. Replacement therapy (e.g. thyroxine for pre-existing hypothyroidism, insulin for type I diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Intra-articular steroid injections are allowed

  • STEP 2: RANDOMIZATION: Participant must have a complete medical history and physical exam within 28 days prior to Step 2: Randomization

  • STEP 2: RANDOMIZATION: Leukocytes >= 3 x 10^3/uL (within 28 days prior to Step 2: Randomization)

  • STEP 2: RANDOMIZATION: Absolute neutrophil count >= 1.5 x 10^3/uL (within 28 days prior to Step 2: Randomization)

  • STEP 2: RANDOMIZATION: Platelets >= 100 x 10^3/uL (within 28 days prior to Step 2: Randomization)

  • STEP 2: RANDOMIZATION: Total bilirubin =< institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN (within 28 days prior to Step 2: Randomization)

  • STEP 2: RANDOMIZATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 × institutional ULN (within 28 days prior to Step 2: Randomization)

  • STEP 2: RANDOMIZATION: Participants must have a calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to Step 2: Randomization

  • STEP 2: RANDOMIZATION: Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better

  • STEP 2: RANDOMIZATION: Participants must not have uncontrolled diabetes defined as hemoglobin A1c of 9.0% or greater, within 28 days prior to Step 2: Randomization

  • STEP 2: RANDOMIZATION: Participants with history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have an undetectable viral load on the most recent test results obtained within 6 months prior to Step 2: Randomization

  • STEP 2: RANDOMIZATION: Participants with history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on the most recent test results obtained while on suppressive therapy within 6 months prior to Step 2: Randomization, if indicated

  • STEP 2: RANDOMIZATION: Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load on the most recent test results obtained within 6 months prior to Step 2: Randomization, if indicated

  • STEP 2: RANDOMIZATION: Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method during protocol therapy and for 6 months following completion of protocol therapy with details provided as a part of the consent process and must have a negative pregnancy test at screening. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen. Participants should not breastfeed during protocol therapy and for 6 months following completion of protocol therapy

  • STEP 2: RANDOMIZATION: Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the SWOG Specimen Tracking System

  • STEP 2: RANDOMIZATION: Participants who can complete questionnaires in English, or Spanish must be offered the opportunity to participate in the Quality of Life study

  • STEP 2: RANDOMIZATION: NOTE: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

  • STEP 2: RANDOMIZATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Step 1 (MammaPrint testing)Genetic TestingPatients without a known MP2 score undergo MammaPrint testing on a previously-collected tissue sample. Patients with MP2 score proceed to STEP 2
Step 2, Arm 1 (chemotherapy)Biospecimen CollectionPatients receive paclitaxel IV on days 1 and 8 of each cycle. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Step 2, Arm 1 (chemotherapy)CyclophosphamidePatients receive paclitaxel IV on days 1 and 8 of each cycle. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Step 2, Arm 1 (chemotherapy)DoxorubicinPatients receive paclitaxel IV on days 1 and 8 of each cycle. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Step 2, Arm 1 (chemotherapy)MammographyPatients receive paclitaxel IV on days 1 and 8 of each cycle. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Step 2, Arm 1 (chemotherapy)PaclitaxelPatients receive paclitaxel IV on days 1 and 8 of each cycle. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Step 2, Arm 1 (chemotherapy)Quality-of-Life AssessmentPatients receive paclitaxel IV on days 1 and 8 of each cycle. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Step 2, Arm 2 (chemotherapy, durvalumab)Biospecimen CollectionPatients receive paclitaxel IV on days 1 and 8 of each cycle and durvalumab IV over 60 minutes on day 1 of cycles 1, 3, and 5. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle, and durvalumab IV over 60 minutes on day 1 of cycles 7 and 9. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Step 2, Arm 2 (chemotherapy, durvalumab)CyclophosphamidePatients receive paclitaxel IV on days 1 and 8 of each cycle and durvalumab IV over 60 minutes on day 1 of cycles 1, 3, and 5. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle, and durvalumab IV over 60 minutes on day 1 of cycles 7 and 9. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Step 2, Arm 2 (chemotherapy, durvalumab)DoxorubicinPatients receive paclitaxel IV on days 1 and 8 of each cycle and durvalumab IV over 60 minutes on day 1 of cycles 1, 3, and 5. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle, and durvalumab IV over 60 minutes on day 1 of cycles 7 and 9. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Step 2, Arm 2 (chemotherapy, durvalumab)DurvalumabPatients receive paclitaxel IV on days 1 and 8 of each cycle and durvalumab IV over 60 minutes on day 1 of cycles 1, 3, and 5. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle, and durvalumab IV over 60 minutes on day 1 of cycles 7 and 9. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Step 2, Arm 2 (chemotherapy, durvalumab)MammographyPatients receive paclitaxel IV on days 1 and 8 of each cycle and durvalumab IV over 60 minutes on day 1 of cycles 1, 3, and 5. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle, and durvalumab IV over 60 minutes on day 1 of cycles 7 and 9. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Step 2, Arm 2 (chemotherapy, durvalumab)PaclitaxelPatients receive paclitaxel IV on days 1 and 8 of each cycle and durvalumab IV over 60 minutes on day 1 of cycles 1, 3, and 5. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle, and durvalumab IV over 60 minutes on day 1 of cycles 7 and 9. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Step 2, Arm 2 (chemotherapy, durvalumab)Quality-of-Life AssessmentPatients receive paclitaxel IV on days 1 and 8 of each cycle and durvalumab IV over 60 minutes on day 1 of cycles 1, 3, and 5. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle, and durvalumab IV over 60 minutes on day 1 of cycles 7 and 9. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at SOC surgery and undergo collection of blood samples throughout the study.
Primary Outcome Measures
NameTimeMethod
Breast cancer event-free survival (BC-EFS)Up to 10 years after completion of study treatment

Defined as the earliest occurrence of any of the following events: Local-regional or distant progression during neoadjuvant therapy or local/regional, or distant invasive breast tumor recurrence post-surgery, invasive ipsilateral breast tumor recurrence, new invasive contralateral breast cancer, or death from any cause. The primary analysis of BC-EFS is a log-rank test between the treatment arms with stratification by the three stratification factors. Additionally, Cox regression will be used to estimate the treatment hazard ratio and 95% confidence interval including the three stratification variables as terms in the model. Kaplan-Meier graphs will show BC-EFS descriptively over time and provide 5-year estimates and 95% confidence intervals. A forest plot will show whether the treatment effect varies over the stratification variables and other selected factors.

Secondary Outcome Measures
NameTimeMethod
Pathologic complete response (pCR) ratesUp to 10 years after completion of study treatment

Defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast and specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ypT0/Tis ypN0). At the completion of all treatment and surgery for all enrolled participants, there will be a comparison of pCR rates between the treatment arms. pCR rates will be compared by a test of two proportions followed by logistic regression to estimate the odds ratio after adjustment for the stratification factors.

Residual cancer burden (RCB)Up to 10 years after completion of study treatment

Defined as a continuous measure of the extent of residual cancer after neoadjuvant chemotherapy that combines the largest diameter of the cancer in the breast, the tumor cell cellularity of the cancer, and the largest diameter and number of involved axillary lymph nodes into a single RCB score. RCB will be analyzed by comparing RCB 2-3 to RCB 0-1.

Distant relapse-free survival (DRFS)Time from date of randomization (2nd Registration) to date of invasive distant disease recurrence or death due to any cause, assessed up to 10 years after completion of study treatment

Analyses will be performed using log-rank testing, Cox regression, and Kaplan-Meier estimation.

Overall survival (OS)Time from date of randomization (2nd Registration) to date of death due to any cause, assessed up to 10 years after completion of study treatment

Analyses will be performed using log-rank testing, Cox regression, and Kaplan-Meier estimation. Will also be conducted at alpha = 0.05 (2-sided).

Trial Locations

Locations (463)

Banner University Medical Center - Tucson

🇺🇸

Tucson, Arizona, United States

University of Arizona Cancer Center-North Campus

🇺🇸

Tucson, Arizona, United States

Mercy Hospital Fort Smith

🇺🇸

Fort Smith, Arkansas, United States

NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro

🇺🇸

Jonesboro, Arkansas, United States

Sutter Auburn Faith Hospital

🇺🇸

Auburn, California, United States

AIS Cancer Center at San Joaquin Community Hospital

🇺🇸

Bakersfield, California, United States

Alta Bates Summit Medical Center-Herrick Campus

🇺🇸

Berkeley, California, United States

Tower Cancer Research Foundation

🇺🇸

Beverly Hills, California, United States

City of Hope Comprehensive Cancer Center

🇺🇸

Duarte, California, United States

Palo Alto Medical Foundation-Fremont

🇺🇸

Fremont, California, United States

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

🇺🇸

Irvine, California, United States

City of Hope at Irvine Lennar

🇺🇸

Irvine, California, United States

City of Hope Antelope Valley

🇺🇸

Lancaster, California, United States

Loma Linda University Medical Center

🇺🇸

Loma Linda, California, United States

City of Hope at Long Beach Elm

🇺🇸

Long Beach, California, United States

Cedars Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Memorial Medical Center

🇺🇸

Modesto, California, United States

City of Hope Newport Beach

🇺🇸

Newport Beach, California, United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

🇺🇸

Orange, California, United States

Desert Regional Medical Center

🇺🇸

Palm Springs, California, United States

Palo Alto Medical Foundation Health Care

🇺🇸

Palo Alto, California, United States

Huntington Memorial Hospital

🇺🇸

Pasadena, California, United States

Sutter Roseville Medical Center

🇺🇸

Roseville, California, United States

Sutter Medical Center Sacramento

🇺🇸

Sacramento, California, United States

Zuckerberg San Francisco General Hospital

🇺🇸

San Francisco, California, United States

California Pacific Medical Center-Pacific Campus

🇺🇸

San Francisco, California, United States

Palo Alto Medical Foundation-Santa Cruz

🇺🇸

Santa Cruz, California, United States

Providence Medical Foundation - Santa Rosa

🇺🇸

Santa Rosa, California, United States

Sutter Pacific Medical Foundation

🇺🇸

Santa Rosa, California, United States

Providence Santa Rosa Memorial Hospital

🇺🇸

Santa Rosa, California, United States

City of Hope South Pasadena

🇺🇸

South Pasadena, California, United States

Palo Alto Medical Foundation-Sunnyvale

🇺🇸

Sunnyvale, California, United States

Cedars-Sinai Cancer - Tarzana

🇺🇸

Tarzana, California, United States

City of Hope South Bay

🇺🇸

Torrance, California, United States

Torrance Memorial Physician Network - Cancer Care

🇺🇸

Torrance, California, United States

City of Hope Upland

🇺🇸

Upland, California, United States

Sutter Solano Medical Center/Cancer Center

🇺🇸

Vallejo, California, United States

UCHealth University of Colorado Hospital

🇺🇸

Aurora, Colorado, United States

UCHealth - Cherry Creek

🇺🇸

Denver, Colorado, United States

Shaw Cancer Center

🇺🇸

Edwards, Colorado, United States

UCHealth Highlands Ranch Hospital

🇺🇸

Highlands Ranch, Colorado, United States

UCHealth Lone Tree Health Center

🇺🇸

Lone Tree, Colorado, United States

Smilow Cancer Hospital-Derby Care Center

🇺🇸

Derby, Connecticut, United States

Smilow Cancer Hospital Care Center-Fairfield

🇺🇸

Fairfield, Connecticut, United States

Smilow Cancer Hospital Care Center at Glastonbury

🇺🇸

Glastonbury, Connecticut, United States

Smilow Cancer Hospital Care Center at Greenwich

🇺🇸

Greenwich, Connecticut, United States

Smilow Cancer Hospital Care Center - Guilford

🇺🇸

Guilford, Connecticut, United States

Smilow Cancer Hospital Care Center at Saint Francis

🇺🇸

Hartford, Connecticut, United States

Yale University

🇺🇸

New Haven, Connecticut, United States

Yale-New Haven Hospital North Haven Medical Center

🇺🇸

North Haven, Connecticut, United States

Smilow Cancer Hospital Care Center at Long Ridge

🇺🇸

Stamford, Connecticut, United States

Smilow Cancer Hospital-Torrington Care Center

🇺🇸

Torrington, Connecticut, United States

Smilow Cancer Hospital Care Center-Trumbull

🇺🇸

Trumbull, Connecticut, United States

Smilow Cancer Hospital-Waterbury Care Center

🇺🇸

Waterbury, Connecticut, United States

Smilow Cancer Hospital Care Center - Waterford

🇺🇸

Waterford, Connecticut, United States

Beebe South Coastal Health Campus

🇺🇸

Millville, Delaware, United States

Helen F Graham Cancer Center

🇺🇸

Newark, Delaware, United States

Medical Oncology Hematology Consultants PA

🇺🇸

Newark, Delaware, United States

Beebe Health Campus

🇺🇸

Rehoboth Beach, Delaware, United States

Sibley Memorial Hospital

🇺🇸

Washington, District of Columbia, United States

Morton Plant Hospital

🇺🇸

Clearwater, Florida, United States

Jupiter Medical Center

🇺🇸

Jupiter, Florida, United States

Mount Sinai Medical Center

🇺🇸

Miami Beach, Florida, United States

Mease Countryside Hospital

🇺🇸

Safety Harbor, Florida, United States

Saint Joseph's Hospital/Children's Hospital-Tampa

🇺🇸

Tampa, Florida, United States

Winter Haven Hospital

🇺🇸

Winter Haven, Florida, United States

Grady Health System

🇺🇸

Atlanta, Georgia, United States

Emory University Hospital Midtown

🇺🇸

Atlanta, Georgia, United States

Emory University Hospital/Winship Cancer Institute

🇺🇸

Atlanta, Georgia, United States

Emory Saint Joseph's Hospital

🇺🇸

Atlanta, Georgia, United States

Emory Decatur Hospital

🇺🇸

Decatur, Georgia, United States

Emory Johns Creek Hospital

🇺🇸

Johns Creek, Georgia, United States

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

🇺🇸

Savannah, Georgia, United States

Saint Alphonsus Cancer Care Center-Boise

🇺🇸

Boise, Idaho, United States

Saint Luke's Cancer Institute - Boise

🇺🇸

Boise, Idaho, United States

Saint Alphonsus Cancer Care Center-Caldwell

🇺🇸

Caldwell, Idaho, United States

Kootenai Health - Coeur d'Alene

🇺🇸

Coeur d'Alene, Idaho, United States

Saint Luke's Cancer Institute - Fruitland

🇺🇸

Fruitland, Idaho, United States

Saint Luke's Cancer Institute - Meridian

🇺🇸

Meridian, Idaho, United States

Saint Alphonsus Cancer Care Center-Nampa

🇺🇸

Nampa, Idaho, United States

Saint Luke's Cancer Institute - Nampa

🇺🇸

Nampa, Idaho, United States

Kootenai Clinic Cancer Services - Post Falls

🇺🇸

Post Falls, Idaho, United States

Kootenai Clinic Cancer Services - Sandpoint

🇺🇸

Sandpoint, Idaho, United States

Advocate Good Shepherd Hospital

🇺🇸

Barrington, Illinois, United States

Illinois CancerCare-Bloomington

🇺🇸

Bloomington, Illinois, United States

Illinois CancerCare-Canton

🇺🇸

Canton, Illinois, United States

Illinois CancerCare-Carthage

🇺🇸

Carthage, Illinois, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

University of Illinois

🇺🇸

Chicago, Illinois, United States

Advocate Illinois Masonic Medical Center

🇺🇸

Chicago, Illinois, United States

AMG Crystal Lake - Oncology

🇺🇸

Crystal Lake, Illinois, United States

Carle at The Riverfront

🇺🇸

Danville, Illinois, United States

Cancer Care Specialists of Illinois - Decatur

🇺🇸

Decatur, Illinois, United States

Decatur Memorial Hospital

🇺🇸

Decatur, Illinois, United States

Northwestern Medicine Cancer Center Kishwaukee

🇺🇸

DeKalb, Illinois, United States

Illinois CancerCare-Dixon

🇺🇸

Dixon, Illinois, United States

Advocate Good Samaritan Hospital

🇺🇸

Downers Grove, Illinois, United States

Carle Physician Group-Effingham

🇺🇸

Effingham, Illinois, United States

Crossroads Cancer Center

🇺🇸

Effingham, Illinois, United States

Advocate Sherman Hospital

🇺🇸

Elgin, Illinois, United States

Illinois CancerCare-Eureka

🇺🇸

Eureka, Illinois, United States

Illinois CancerCare-Galesburg

🇺🇸

Galesburg, Illinois, United States

Northwestern Medicine Cancer Center Delnor

🇺🇸

Geneva, Illinois, United States

Northwestern Medicine Glenview Outpatient Center

🇺🇸

Glenview, Illinois, United States

Northwestern Medicine Grayslake Outpatient Center

🇺🇸

Grayslake, Illinois, United States

Advocate South Suburban Hospital

🇺🇸

Hazel Crest, Illinois, United States

Illinois CancerCare-Kewanee Clinic

🇺🇸

Kewanee, Illinois, United States

Northwestern Medicine Lake Forest Hospital

🇺🇸

Lake Forest, Illinois, United States

AMG Libertyville - Oncology

🇺🇸

Libertyville, Illinois, United States

Condell Memorial Hospital

🇺🇸

Libertyville, Illinois, United States

Illinois CancerCare-Macomb

🇺🇸

Macomb, Illinois, United States

Carle Physician Group-Mattoon/Charleston

🇺🇸

Mattoon, Illinois, United States

Loyola University Medical Center

🇺🇸

Maywood, Illinois, United States

Trinity Medical Center

🇺🇸

Moline, Illinois, United States

SSM Health Good Samaritan

🇺🇸

Mount Vernon, Illinois, United States

Cancer Care Center of O'Fallon

🇺🇸

O'Fallon, Illinois, United States

Advocate Christ Medical Center

🇺🇸

Oak Lawn, Illinois, United States

Northwestern Medicine Orland Park

🇺🇸

Orland Park, Illinois, United States

Illinois CancerCare-Ottawa Clinic

🇺🇸

Ottawa, Illinois, United States

Advocate Lutheran General Hospital

🇺🇸

Park Ridge, Illinois, United States

Illinois CancerCare-Pekin

🇺🇸

Pekin, Illinois, United States

Illinois CancerCare-Peoria

🇺🇸

Peoria, Illinois, United States

Illinois CancerCare-Peru

🇺🇸

Peru, Illinois, United States

Illinois CancerCare-Princeton

🇺🇸

Princeton, Illinois, United States

UW Health Carbone Cancer Center Rockford

🇺🇸

Rockford, Illinois, United States

Memorial Hospital East

🇺🇸

Shiloh, Illinois, United States

Southern Illinois University School of Medicine

🇺🇸

Springfield, Illinois, United States

Springfield Clinic

🇺🇸

Springfield, Illinois, United States

Springfield Memorial Hospital

🇺🇸

Springfield, Illinois, United States

Carle Cancer Center

🇺🇸

Urbana, Illinois, United States

Northwestern Medicine Cancer Center Warrenville

🇺🇸

Warrenville, Illinois, United States

Illinois CancerCare - Washington

🇺🇸

Washington, Illinois, United States

Northwest Cancer Center - Main Campus

🇺🇸

Crown Point, Indiana, United States

Northwest Oncology LLC

🇺🇸

Dyer, Indiana, United States

Northwest Cancer Center - Hobart

🇺🇸

Hobart, Indiana, United States

Saint Mary Medical Center

🇺🇸

Hobart, Indiana, United States

Saint Catherine Hospital

🇺🇸

Indianapolis, Indiana, United States

The Community Hospital

🇺🇸

Munster, Indiana, United States

Women's Diagnostic Center - Munster

🇺🇸

Munster, Indiana, United States

Northwest Cancer Center - Valparaiso

🇺🇸

Valparaiso, Indiana, United States

UI Health Care Mission Cancer and Blood - Ankeny Clinic

🇺🇸

Ankeny, Iowa, United States

Saint Anthony Regional Hospital

🇺🇸

Carroll, Iowa, United States

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

🇺🇸

Clive, Iowa, United States

Iowa Methodist Medical Center

🇺🇸

Des Moines, Iowa, United States

UI Health Care Mission Cancer and Blood - Des Moines Clinic

🇺🇸

Des Moines, Iowa, United States

Broadlawns Medical Center

🇺🇸

Des Moines, Iowa, United States

Mercy Medical Center - Des Moines

🇺🇸

Des Moines, Iowa, United States

UI Health Care Mission Cancer and Blood - Laurel Clinic

🇺🇸

Des Moines, Iowa, United States

Trinity Regional Medical Center

🇺🇸

Fort Dodge, Iowa, United States

HaysMed

🇺🇸

Hays, Kansas, United States

University of Kansas Cancer Center

🇺🇸

Kansas City, Kansas, United States

Lawrence Memorial Hospital

🇺🇸

Lawrence, Kansas, United States

The University of Kansas Cancer Center - Olathe

🇺🇸

Olathe, Kansas, United States

University of Kansas Cancer Center-Overland Park

🇺🇸

Overland Park, Kansas, United States

University of Kansas Hospital-Indian Creek Campus

🇺🇸

Overland Park, Kansas, United States

Salina Regional Health Center

🇺🇸

Salina, Kansas, United States

University of Kansas Health System Saint Francis Campus

🇺🇸

Topeka, Kansas, United States

University of Kansas Hospital-Westwood Cancer Center

🇺🇸

Westwood, Kansas, United States

Saint Joseph Hospital East

🇺🇸

Lexington, Kentucky, United States

University of Kentucky/Markey Cancer Center

🇺🇸

Lexington, Kentucky, United States

Ochsner LSU Health Monroe Medical Center

🇺🇸

Monroe, Louisiana, United States

LSU Health Sciences Center at Shreveport

🇺🇸

Shreveport, Louisiana, United States

Ochsner LSU Health - Cancer Treatment Center

🇺🇸

Shreveport, Louisiana, United States

UM Upper Chesapeake Hematology and Oncology - Aberdeen

🇺🇸

Aberdeen, Maryland, United States

University of Maryland/Greenebaum Cancer Center

🇺🇸

Baltimore, Maryland, United States

Mercy Medical Center

🇺🇸

Baltimore, Maryland, United States

Sinai Hospital of Baltimore

🇺🇸

Baltimore, Maryland, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

🇺🇸

Baltimore, Maryland, United States

UM Upper Chesapeake Medical Center

🇺🇸

Bel Air, Maryland, United States

UPMC Western Maryland

🇺🇸

Cumberland, Maryland, United States

UM Baltimore Washington Medical Center/Tate Cancer Center

🇺🇸

Glen Burnie, Maryland, United States

William E Kahlert Regional Cancer Center/Sinai Hospital

🇺🇸

Westminster, Maryland, United States

Beverly Hospital

🇺🇸

Beverly, Massachusetts, United States

Lahey Hospital and Medical Center

🇺🇸

Burlington, Massachusetts, United States

Addison Gilbert Hospital

🇺🇸

Gloucester, Massachusetts, United States

Lahey Medical Center-Peabody

🇺🇸

Peabody, Massachusetts, United States

Trinity Health Saint Joseph Mercy Hospital Ann Arbor

🇺🇸

Ann Arbor, Michigan, United States

University of Michigan Comprehensive Cancer Center

🇺🇸

Ann Arbor, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Brighton

🇺🇸

Brighton, Michigan, United States

Trinity Health Medical Center - Brighton

🇺🇸

Brighton, Michigan, United States

University of Michigan - Brighton Center for Specialty Care

🇺🇸

Brighton, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Canton

🇺🇸

Canton, Michigan, United States

Trinity Health Medical Center - Canton

🇺🇸

Canton, Michigan, United States

Caro Cancer Center

🇺🇸

Caro, Michigan, United States

Chelsea Hospital

🇺🇸

Chelsea, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

🇺🇸

Chelsea, Michigan, United States

Henry Ford Macomb Hospital-Clinton Township

🇺🇸

Clinton Township, Michigan, United States

Corewell Health Dearborn Hospital

🇺🇸

Dearborn, Michigan, United States

Wayne State University/Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Henry Ford Health Saint John Hospital

🇺🇸

Detroit, Michigan, United States

Henry Ford River District Hospital

🇺🇸

East China Township, Michigan, United States

OSF Saint Francis Hospital and Medical Group

🇺🇸

Escanaba, Michigan, United States

Weisberg Cancer Treatment Center

🇺🇸

Farmington Hills, Michigan, United States

Corewell Health Farmington Hills Hospital

🇺🇸

Farmington Hills, Michigan, United States

Cancer Hematology Centers - Flint

🇺🇸

Flint, Michigan, United States

Genesee Hematology Oncology PC

🇺🇸

Flint, Michigan, United States

Genesys Hurley Cancer Institute

🇺🇸

Flint, Michigan, United States

Hurley Medical Center

🇺🇸

Flint, Michigan, United States

Henry Ford Saint John Hospital - Van Elslander

🇺🇸

Grosse Pointe Woods, Michigan, United States

Allegiance Health

🇺🇸

Jackson, Michigan, United States

Karmanos Cancer Institute at McLaren Greater Lansing

🇺🇸

Lansing, Michigan, United States

University of Michigan Health - Sparrow Lansing

🇺🇸

Lansing, Michigan, United States

Trinity Health Saint Mary Mercy Livonia Hospital

🇺🇸

Livonia, Michigan, United States

Henry Ford Saint John Hospital - Macomb Medical

🇺🇸

Macomb, Michigan, United States

Henry Ford Health Providence Novi Hospital

🇺🇸

Novi, Michigan, United States

Henry Ford Medical Center-Columbus

🇺🇸

Novi, Michigan, United States

Trinity Health Saint Joseph Mercy Oakland Hospital

🇺🇸

Pontiac, Michigan, United States

Corewell Health William Beaumont University Hospital

🇺🇸

Royal Oak, Michigan, United States

MyMichigan Medical Center Saginaw

🇺🇸

Saginaw, Michigan, United States

Oncology Hematology Associates of Saginaw Valley PC

🇺🇸

Saginaw, Michigan, United States

Henry Ford Health Providence Southfield Hospital

🇺🇸

Southfield, Michigan, United States

MyMichigan Medical Center Tawas

🇺🇸

Tawas City, Michigan, United States

Corewell Health Beaumont Troy Hospital

🇺🇸

Troy, Michigan, United States

Henry Ford Health Warren Hospital

🇺🇸

Warren, Michigan, United States

Henry Ford Warren Hospital - GLCMS

🇺🇸

Warren, Michigan, United States

Henry Ford West Bloomfield Hospital

🇺🇸

West Bloomfield, Michigan, United States

Saint Mary's Oncology/Hematology Associates of West Branch

🇺🇸

West Branch, Michigan, United States

Huron Gastroenterology PC

🇺🇸

Ypsilanti, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

🇺🇸

Ypsilanti, Michigan, United States

Essentia Health Saint Joseph's Medical Center

🇺🇸

Brainerd, Minnesota, United States

Minnesota Oncology - Burnsville

🇺🇸

Burnsville, Minnesota, United States

Mercy Hospital

🇺🇸

Coon Rapids, Minnesota, United States

Essentia Health - Deer River Clinic

🇺🇸

Deer River, Minnesota, United States

Essentia Health Cancer Center

🇺🇸

Duluth, Minnesota, United States

Saint Luke's Hospital of Duluth

🇺🇸

Duluth, Minnesota, United States

Fairview Southdale Hospital

🇺🇸

Edina, Minnesota, United States

Essentia Health Hibbing Clinic

🇺🇸

Hibbing, Minnesota, United States

Saint John's Hospital - Healtheast

🇺🇸

Maplewood, Minnesota, United States

Abbott-Northwestern Hospital

🇺🇸

Minneapolis, Minnesota, United States

Hennepin County Medical Center

🇺🇸

Minneapolis, Minnesota, United States

North Memorial Medical Health Center

🇺🇸

Robbinsdale, Minnesota, United States

Park Nicollet Clinic - Saint Louis Park

🇺🇸

Saint Louis Park, Minnesota, United States

Regions Hospital

🇺🇸

Saint Paul, Minnesota, United States

United Hospital

🇺🇸

Saint Paul, Minnesota, United States

Essentia Health Sandstone

🇺🇸

Sandstone, Minnesota, United States

Saint Francis Regional Medical Center

🇺🇸

Shakopee, Minnesota, United States

Essentia Health Virginia Clinic

🇺🇸

Virginia, Minnesota, United States

Ridgeview Medical Center

🇺🇸

Waconia, Minnesota, United States

Baptist Memorial Hospital and Cancer Center-Golden Triangle

🇺🇸

Columbus, Mississippi, United States

Baptist Cancer Center-Grenada

🇺🇸

Grenada, Mississippi, United States

Baptist Memorial Hospital and Cancer Center-Union County

🇺🇸

New Albany, Mississippi, United States

Baptist Memorial Hospital and Cancer Center-Oxford

🇺🇸

Oxford, Mississippi, United States

Baptist Memorial Hospital and Cancer Center-Desoto

🇺🇸

Southhaven, Mississippi, United States

Saint Francis Medical Center

🇺🇸

Cape Girardeau, Missouri, United States

MU Health - University Hospital/Ellis Fischel Cancer Center

🇺🇸

Columbia, Missouri, United States

Siteman Cancer Center at West County Hospital

🇺🇸

Creve Coeur, Missouri, United States

Parkland Health Center - Farmington

🇺🇸

Farmington, Missouri, United States

MU Health Care Goldschmidt Cancer Center

🇺🇸

Jefferson City, Missouri, United States

University Health Truman Medical Center

🇺🇸

Kansas City, Missouri, United States

University of Kansas Cancer Center - North

🇺🇸

Kansas City, Missouri, United States

University of Kansas Cancer Center - Lee's Summit

🇺🇸

Lee's Summit, Missouri, United States

University of Kansas Cancer Center at North Kansas City Hospital

🇺🇸

North Kansas City, Missouri, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Mercy Hospital South

🇺🇸

Saint Louis, Missouri, United States

Siteman Cancer Center-South County

🇺🇸

Saint Louis, Missouri, United States

Missouri Baptist Medical Center

🇺🇸

Saint Louis, Missouri, United States

Siteman Cancer Center at Christian Hospital

🇺🇸

Saint Louis, Missouri, United States

Siteman Cancer Center at Saint Peters Hospital

🇺🇸

Saint Peters, Missouri, United States

Sainte Genevieve County Memorial Hospital

🇺🇸

Sainte Genevieve, Missouri, United States

CoxHealth South Hospital

🇺🇸

Springfield, Missouri, United States

Missouri Baptist Sullivan Hospital

🇺🇸

Sullivan, Missouri, United States

BJC Outpatient Center at Sunset Hills

🇺🇸

Sunset Hills, Missouri, United States

Community Hospital of Anaconda

🇺🇸

Anaconda, Montana, United States

Billings Clinic Cancer Center

🇺🇸

Billings, Montana, United States

Bozeman Health Deaconess Hospital

🇺🇸

Bozeman, Montana, United States

Benefis Sletten Cancer Institute

🇺🇸

Great Falls, Montana, United States

Community Medical Center

🇺🇸

Scranton, Pennsylvania, United States

OptumCare Cancer Care at Seven Hills

🇺🇸

Henderson, Nevada, United States

OptumCare Cancer Care at Charleston

🇺🇸

Las Vegas, Nevada, United States

OptumCare Cancer Care at Fort Apache

🇺🇸

Las Vegas, Nevada, United States

Renown Regional Medical Center

🇺🇸

Reno, Nevada, United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

🇺🇸

Lebanon, New Hampshire, United States

Trinitas Hospital and Comprehensive Cancer Center - Williamson Street Campus

🇺🇸

Elizabeth, New Jersey, United States

The Cancer Institute of New Jersey Hamilton

🇺🇸

Hamilton, New Jersey, United States

Jersey City Medical Center

🇺🇸

Jersey City, New Jersey, United States

Monmouth Medical Center Southern Campus

🇺🇸

Lakewood, New Jersey, United States

Monmouth Medical Center

🇺🇸

Long Branch, New Jersey, United States

Rutgers Cancer Institute of New Jersey

🇺🇸

New Brunswick, New Jersey, United States

Rutgers New Jersey Medical School

🇺🇸

Newark, New Jersey, United States

Newark Beth Israel Medical Center

🇺🇸

Newark, New Jersey, United States

Robert Wood Johnson University Hospital Somerset

🇺🇸

Somerville, New Jersey, United States

NYU Langone Hospital - Brooklyn

🇺🇸

Brooklyn, New York, United States

Glens Falls Hospital

🇺🇸

Glens Falls, New York, United States

NYU Langone Hospital - Long Island

🇺🇸

Mineola, New York, United States

Northern Westchester Hospital

🇺🇸

Mount Kisco, New York, United States

Mount Sinai Chelsea

🇺🇸

New York, New York, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

🇺🇸

New York, New York, United States

Mount Sinai West

🇺🇸

New York, New York, United States

Mount Sinai Hospital

🇺🇸

New York, New York, United States

Manhattan Eye Ear and Throat Hospital

🇺🇸

New York, New York, United States

Lenox Hill Hospital

🇺🇸

New York, New York, United States

Upstate Cancer Center at Oswego

🇺🇸

Oswego, New York, United States

Phelps Memorial Hospital Center

🇺🇸

Sleepy Hollow, New York, United States

The Philips Family Cancer Center

🇺🇸

Southampton, New York, United States

Staten Island University Hospital

🇺🇸

Staten Island, New York, United States

Stony Brook University Medical Center

🇺🇸

Stony Brook, New York, United States

State University of New York Upstate Medical University

🇺🇸

Syracuse, New York, United States

SUNY Upstate Medical Center-Community Campus

🇺🇸

Syracuse, New York, United States

Upstate Cancer Center at Verona

🇺🇸

Verona, New York, United States

Dickstein Cancer Treatment Center

🇺🇸

White Plains, New York, United States

Rex Hematology Oncology Associates-Cary

🇺🇸

Cary, North Carolina, United States

Southeastern Medical Oncology Center-Clinton

🇺🇸

Clinton, North Carolina, United States

Rex Hematology Oncology Associates-Garner

🇺🇸

Garner, North Carolina, United States

Southeastern Medical Oncology Center-Goldsboro

🇺🇸

Goldsboro, North Carolina, United States

Southeastern Medical Oncology Center-Jacksonville

🇺🇸

Jacksonville, North Carolina, United States

UNC Rex Healthcare

🇺🇸

Raleigh, North Carolina, United States

UNC Rex Cancer Center of Wakefield

🇺🇸

Raleigh, North Carolina, United States

Essentia Health Cancer Center-South University Clinic

🇺🇸

Fargo, North Dakota, United States

Miami Valley Hospital South

🇺🇸

Centerville, Ohio, United States

MetroHealth Medical Center

🇺🇸

Cleveland, Ohio, United States

Ohio State University Comprehensive Cancer Center

🇺🇸

Columbus, Ohio, United States

Columbus Oncology and Hematology Associates Inc

🇺🇸

Columbus, Ohio, United States

Riverside Methodist Hospital

🇺🇸

Columbus, Ohio, United States

Grant Medical Center

🇺🇸

Columbus, Ohio, United States

Doctors Hospital

🇺🇸

Columbus, Ohio, United States

Miami Valley Hospital

🇺🇸

Dayton, Ohio, United States

Premier Blood and Cancer Center

🇺🇸

Dayton, Ohio, United States

Miami Valley Hospital North

🇺🇸

Dayton, Ohio, United States

Delaware Health Center-Grady Cancer Center

🇺🇸

Delaware, Ohio, United States

Grady Memorial Hospital

🇺🇸

Delaware, Ohio, United States

Columbus Oncology and Hematology Associates

🇺🇸

Dublin, Ohio, United States

Dublin Methodist Hospital

🇺🇸

Dublin, Ohio, United States

Atrium Medical Center-Middletown Regional Hospital

🇺🇸

Franklin, Ohio, United States

Miami Valley Cancer Care and Infusion

🇺🇸

Greenville, Ohio, United States

OhioHealth Mansfield Hospital

🇺🇸

Mansfield, Ohio, United States

OhioHealth Marion General Hospital

🇺🇸

Marion, Ohio, United States

OhioHealth Pickerington Methodist Hospital

🇺🇸

Pickerington, Ohio, United States

ProMedica Flower Hospital

🇺🇸

Sylvania, Ohio, United States

Upper Valley Medical Center

🇺🇸

Troy, Ohio, United States

OhioHealth Westerville Medical Campus/Westerville Cancer Center

🇺🇸

Westerville, Ohio, United States

University of Oklahoma Health Sciences Center

🇺🇸

Oklahoma City, Oklahoma, United States

Mercy Hospital Oklahoma City

🇺🇸

Oklahoma City, Oklahoma, United States

Oklahoma Cancer Specialists and Research Institute-Tulsa

🇺🇸

Tulsa, Oklahoma, United States

Saint Charles Health System

🇺🇸

Bend, Oregon, United States

Legacy Mount Hood Medical Center

🇺🇸

Gresham, Oregon, United States

Providence Hood River Memorial Hospital

🇺🇸

Hood River, Oregon, United States

Providence Newberg Medical Center

🇺🇸

Newberg, Oregon, United States

Saint Alphonsus Cancer Care Center-Ontario

🇺🇸

Ontario, Oregon, United States

Providence Willamette Falls Medical Center

🇺🇸

Oregon City, Oregon, United States

Legacy Good Samaritan Hospital and Medical Center

🇺🇸

Portland, Oregon, United States

Providence Portland Medical Center

🇺🇸

Portland, Oregon, United States

Providence Saint Vincent Medical Center

🇺🇸

Portland, Oregon, United States

SWOG

🇺🇸

Portland, Oregon, United States

Legacy Meridian Park Hospital

🇺🇸

Tualatin, Oregon, United States

Saint Luke's Cancer Center - Allentown

🇺🇸

Allentown, Pennsylvania, United States

UPMC-Heritage Valley Health System Beaver

🇺🇸

Beaver, Pennsylvania, United States

Saint Luke's University Hospital-Bethlehem Campus

🇺🇸

Bethlehem, Pennsylvania, United States

Bryn Mawr Hospital

🇺🇸

Bryn Mawr, Pennsylvania, United States

UPMC Hillman Cancer Center at Butler Health System

🇺🇸

Butler, Pennsylvania, United States

UPMC Hillman Cancer Center - Passavant - Cranberry

🇺🇸

Cranberry Township, Pennsylvania, United States

Geisinger Medical Center

🇺🇸

Danville, Pennsylvania, United States

Saint Luke's Hospital-Anderson Campus

🇺🇸

Easton, Pennsylvania, United States

UPMC Hillman Cancer Center Erie

🇺🇸

Erie, Pennsylvania, United States

Saint Vincent Hospital

🇺🇸

Erie, Pennsylvania, United States

UPMC Cancer Centers - Arnold Palmer Pavilion

🇺🇸

Greensburg, Pennsylvania, United States

UPMC Pinnacle Cancer Center/Community Osteopathic Campus

🇺🇸

Harrisburg, Pennsylvania, United States

IRMC Cancer Center

🇺🇸

Indiana, Pennsylvania, United States

Jefferson Hospital

🇺🇸

Jefferson Hills, Pennsylvania, United States

UPMC-Johnstown/John P. Murtha Regional Cancer Center

🇺🇸

Johnstown, Pennsylvania, United States

Geisinger Medical Oncology-Lewisburg

🇺🇸

Lewisburg, Pennsylvania, United States

UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion

🇺🇸

Mechanicsburg, Pennsylvania, United States

Riddle Memorial Hospital

🇺🇸

Media, Pennsylvania, United States

Forbes Hospital

🇺🇸

Monroeville, Pennsylvania, United States

UPMC Hillman Cancer Center in Coraopolis

🇺🇸

Moon, Pennsylvania, United States

Paoli Memorial Hospital

🇺🇸

Paoli, Pennsylvania, United States

Allegheny General Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

UPMC-Magee Womens Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

UPMC-Saint Margaret

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Cancer Institute (UPCI)

🇺🇸

Pittsburgh, Pennsylvania, United States

UPMC-Passavant Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

UPMC-Saint Clair Hospital Cancer Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Saint Luke's Hospital - Upper Bucks Campus

🇺🇸

Quakertown, Pennsylvania, United States

Saint Luke's Hospital - Monroe Campus

🇺🇸

Stroudsburg, Pennsylvania, United States

UPMC Cancer Center-Washington

🇺🇸

Washington, Pennsylvania, United States

UPMC West Mifflin-Cancer Center Jefferson

🇺🇸

West Mifflin, Pennsylvania, United States

Wexford Health and Wellness Pavilion

🇺🇸

Wexford, Pennsylvania, United States

Geisinger Wyoming Valley/Henry Cancer Center

🇺🇸

Wilkes-Barre, Pennsylvania, United States

Divine Providence Hospital

🇺🇸

Williamsport, Pennsylvania, United States

Lankenau Medical Center

🇺🇸

Wynnewood, Pennsylvania, United States

UPMC Memorial

🇺🇸

York, Pennsylvania, United States

Women and Infants Hospital

🇺🇸

Providence, Rhode Island, United States

Smilow Cancer Hospital Care Center - Westerly

🇺🇸

Westerly, Rhode Island, United States

Saint Joseph's/Candler - Bluffton Campus

🇺🇸

Bluffton, South Carolina, United States

Prisma Health Cancer Institute - Spartanburg

🇺🇸

Boiling Springs, South Carolina, United States

Roper Hospital

🇺🇸

Charleston, South Carolina, United States

Charleston Oncology - Roper

🇺🇸

Charleston, South Carolina, United States

Bon Secours Saint Francis Hospital

🇺🇸

Charleston, South Carolina, United States

Charleston Oncology - Saint Francis

🇺🇸

Charleston, South Carolina, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Prisma Health Cancer Institute - Easley

🇺🇸

Easley, South Carolina, United States

Tidelands Georgetown Memorial Hospital

🇺🇸

Georgetown, South Carolina, United States

Prisma Health Cancer Institute - Butternut

🇺🇸

Greenville, South Carolina, United States

Prisma Health Cancer Institute - Faris

🇺🇸

Greenville, South Carolina, United States

Prisma Health Greenville Memorial Hospital

🇺🇸

Greenville, South Carolina, United States

Prisma Health Cancer Institute - Eastside

🇺🇸

Greenville, South Carolina, United States

Prisma Health Cancer Institute - Greer

🇺🇸

Greer, South Carolina, United States

South Carolina Cancer Specialists PC

🇺🇸

Hilton Head Island, South Carolina, United States

Prisma Health Cancer Institute - Seneca

🇺🇸

Seneca, South Carolina, United States

Baptist Memorial Hospital and Cancer Center-Collierville

🇺🇸

Collierville, Tennessee, United States

Thompson Cancer Survival Center

🇺🇸

Knoxville, Tennessee, United States

Thompson Cancer Survival Center - West

🇺🇸

Knoxville, Tennessee, United States

Baptist Memorial Hospital and Cancer Center-Memphis

🇺🇸

Memphis, Tennessee, United States

Thompson Oncology Group-Oak Ridge

🇺🇸

Oak Ridge, Tennessee, United States

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

🇺🇸

Houston, Texas, United States

Ben Taub General Hospital

🇺🇸

Houston, Texas, United States

M D Anderson Cancer Center

🇺🇸

Houston, Texas, United States

University of Texas Health Science Center at San Antonio

🇺🇸

San Antonio, Texas, United States

Hematology Oncology Associates of Fredericksburg Inc

🇺🇸

Fredericksburg, Virginia, United States

Bon Secours Memorial Regional Medical Center

🇺🇸

Mechanicsville, Virginia, United States

Bon Secours Saint Francis Medical Center

🇺🇸

Midlothian, Virginia, United States

Bon Secours Saint Mary's Hospital

🇺🇸

Richmond, Virginia, United States

Virginia Cancer Institute

🇺🇸

Richmond, Virginia, United States

VCU Massey Cancer Center at Stony Point

🇺🇸

Richmond, Virginia, United States

Virginia Commonwealth University/Massey Cancer Center

🇺🇸

Richmond, Virginia, United States

VCU Community Memorial Health Center

🇺🇸

South Hill, Virginia, United States

Swedish Cancer Institute-Edmonds

🇺🇸

Edmonds, Washington, United States

Swedish Cancer Institute-Issaquah

🇺🇸

Issaquah, Washington, United States

Providence Regional Cancer System-Lacey

🇺🇸

Lacey, Washington, United States

Swedish Medical Center-First Hill

🇺🇸

Seattle, Washington, United States

Northwest Medical Specialties PLLC

🇺🇸

Tacoma, Washington, United States

Legacy Cancer Institute Medical Oncology and Day Treatment

🇺🇸

Vancouver, Washington, United States

Legacy Salmon Creek Hospital

🇺🇸

Vancouver, Washington, United States

West Virginia University Charleston Division

🇺🇸

Charleston, West Virginia, United States

West Virginia University Healthcare

🇺🇸

Morgantown, West Virginia, United States

ThedaCare Regional Cancer Center

🇺🇸

Appleton, Wisconsin, United States

Duluth Clinic Ashland

🇺🇸

Ashland, Wisconsin, United States

Aurora Cancer Care-Southern Lakes VLCC

🇺🇸

Burlington, Wisconsin, United States

Aurora Saint Luke's South Shore

🇺🇸

Cudahy, Wisconsin, United States

Marshfield Medical Center-EC Cancer Center

🇺🇸

Eau Claire, Wisconsin, United States

Aurora Health Care Germantown Health Center

🇺🇸

Germantown, Wisconsin, United States

Aurora Cancer Care-Grafton

🇺🇸

Grafton, Wisconsin, United States

Bellin Memorial Hospital

🇺🇸

Green Bay, Wisconsin, United States

Saint Vincent Hospital Cancer Center Green Bay

🇺🇸

Green Bay, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Saint Mary's

🇺🇸

Green Bay, Wisconsin, United States

Aurora BayCare Medical Center

🇺🇸

Green Bay, Wisconsin, United States

Aurora Cancer Care-Kenosha South

🇺🇸

Kenosha, Wisconsin, United States

Aurora Bay Area Medical Group-Marinette

🇺🇸

Marinette, Wisconsin, United States

Marshfield Medical Center-Marshfield

🇺🇸

Marshfield, Wisconsin, United States

Froedtert Menomonee Falls Hospital

🇺🇸

Menomonee Falls, Wisconsin, United States

Aurora Cancer Care-Milwaukee

🇺🇸

Milwaukee, Wisconsin, United States

Aurora Saint Luke's Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Aurora Sinai Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

Marshfield Medical Center - Minocqua

🇺🇸

Minocqua, Wisconsin, United States

ThedaCare Regional Medical Center - Neenah

🇺🇸

Neenah, Wisconsin, United States

Drexel Town Square Health Center

🇺🇸

Oak Creek, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Oconto Falls

🇺🇸

Oconto Falls, Wisconsin, United States

Vince Lombardi Cancer Clinic - Oshkosh

🇺🇸

Oshkosh, Wisconsin, United States

Aurora Cancer Care-Racine

🇺🇸

Racine, Wisconsin, United States

Marshfield Medical Center-Rice Lake

🇺🇸

Rice Lake, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Sheboygan

🇺🇸

Sheboygan, Wisconsin, United States

Vince Lombardi Cancer Clinic-Sheboygan

🇺🇸

Sheboygan, Wisconsin, United States

Marshfield Medical Center-River Region at Stevens Point

🇺🇸

Stevens Point, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Sturgeon Bay

🇺🇸

Sturgeon Bay, Wisconsin, United States

Aurora Medical Center in Summit

🇺🇸

Summit, Wisconsin, United States

Vince Lombardi Cancer Clinic-Two Rivers

🇺🇸

Two Rivers, Wisconsin, United States

Aurora Cancer Care-Milwaukee West

🇺🇸

Wauwatosa, Wisconsin, United States

Aurora West Allis Medical Center

🇺🇸

West Allis, Wisconsin, United States

Froedtert West Bend Hospital/Kraemer Cancer Center

🇺🇸

West Bend, Wisconsin, United States

Marshfield Medical Center - Weston

🇺🇸

Weston, Wisconsin, United States

Centro Comprensivo de Cancer de UPR

🇵🇷

San Juan, Puerto Rico

PROncology

🇵🇷

San Juan, Puerto Rico

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