Evaluating the Addition of the Immunotherapy Drug Atezolizumab to Standard Chemotherapy Treatment for Advanced or Metastatic Neuroendocrine Carcinomas That Originate Outside the Lung
- Conditions
- Advanced Extrapulmonary Neuroendocrine CarcinomaMetastatic Extrapulmonary Neuroendocrine CarcinomaRecurrent Extrapulmonary Neuroendocrine CarcinomaUnresectable Extrapulmonary Neuroendocrine Carcinoma
- Interventions
- Procedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingOther: Patient Observation
- Registration Number
- NCT05058651
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II/III trial compares the effect of immunotherapy with atezolizumab in combination with standard chemotherapy with a platinum drug (cisplatin or carboplatin) and etoposide versus standard therapy alone for the treatment of poorly differentiated extrapulmonary (originated outside the lung) neuroendocrine cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). The other aim of this trial is to compare using atezolizumab just at the beginning of treatment versus continuing it beyond the initial treatment. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. Giving atezolizumab in combination with a platinum drug (cisplatin or carboplatin) and etoposide may work better in treating patients with poorly differentiated extrapulmonary neuroendocrine cancer compared to standard therapy with a platinum drug (cisplatin or carboplatin) and etoposide alone.
- Detailed Description
PRIMARY OBJECTIVES:
I. Compare the combination of induction platinum/etoposide and atezolizumab followed by maintenance atezolizumab (Arm 1) versus induction platinum/etoposide alone (Arm 3).
II. Compare the combination of induction platinum/etoposide and atezolizumab followed by observation (Arm 2) versus induction platinum/etoposide alone (Arm 3).
III. Compare the combination of induction platinum/etoposide and atezolizumab followed by maintenance atezolizumab (Arm 1) versus the combination of induction platinum/etoposide and atezolizumab followed by observation (Arm 2).
SECONDARY OBJECTIVES:
I. To compare overall survival (OS), measured from start of observation/maintenance, across arms.
II. To compare progression free survival (PFS) (measured from randomization and measured from start of observation/maintenance) across arms.
III. To compare objective response rate (ORR = confirmed and unconfirmed partial response \[PR\] + confirmed and unconfirmed complete response \[CR\]) across arms among patients with measurable disease at randomization.
IV. To compare clinical benefit rate (CBR = confirmed and unconfirmed PR + confirmed and unconfirmed CR + stable disease \[SD\]) across arms among patients with measurable disease at randomization.
V. To compare duration of response (DOR) across arms. VI. To evaluate the safety and tolerability of each arm.
ADDITIONAL OBJECTIVE:
I. To bank tumor and blood samples for future biomarker correlative studies.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM I: During induction phase, patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. During maintenance phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity.
ARM II: During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year.
ARM III: During induction phase, patients receive carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year.
Patients in all arms also undergo compute tomography (CT) scan and/or magnetic resonance imaging (MRI) throughout the trial and blood sample collection on study.
After completion of study treatment, patients are followed up for 5 years.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 189
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Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC)
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Participants must have disease that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator
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Participants must have radiologically evaluable disease, measurable or non-measurable, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. All measurable and nonmeasurable lesions must be assessed by CT scan with IV contrast of the chest/abdomen/and pelvis (or CT chest without contrast and MRI abdomen/pelvis with gadolinium contrast, if contraindication to CT iodinated contrast) within 28 days prior to registration. While may be used for routine clinical evaluation, PET scans and bone scans alone are not acceptable for disease assessment while participating in this study. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form
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Participants must have brain MRI (or CT head with contrast if there is contraindication to MRI brain) if clinically indicated within 28 days prior to registration. Note: Brain imaging is not required in participants without known and/or clinical concern for brain metastases. Participants with asymptomatic central nervous system (CNS) metastases are eligible if one or more of the following apply:
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Participants who have received treatment for brain metastases must have:
- No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
- Discontinued all corticosteroids at least 14 days prior to registration
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Participants with treatment-naive brain lesions must have:
- No lesion measuring > 2.0 cm in size in any axis
- MRI brain or CT head with contrast (if there is contraindication to MRI brain) demonstrating no evidence for mass effect, edema, or other impending neurological compromise within 28 days prior to registration
- No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
- No need for > 2 mg of dexamethasone (or equivalent of > 10 mg prednisone) per day at time of registration
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Participants must not have symptomatic central nervous system (CNS) metastases
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Participants must not have known or suspected leptomeningeal disease
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Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinum-based therapy +/- radiation +/- surgery provided that all therapy was completed >= 6 months prior to registration
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Participants must discontinue denosumab prior to study registration and plan to replace with a bisphosphonate while on the study
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Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed >= 24 weeks prior to registration and participants have recovered from all prior toxicities to =< grade 1.
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Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, antiPD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least 12 months prior to study registration
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Participants must not have received treatment with systemic immunostimulatory agents including, but not limited to, interferon and interleukin2 [IL-2] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to registration
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Participants must not have had history of known severe allergy, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, including to Chinese hamster ovary cell products or to any component of the atezolizumab formulation, cisplatin, carboplatin, or etoposide
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Participants must not be on active systemic therapy for another cancer with the exception of hormonal therapy including androgen deprivation therapy (e.g., gonadotropin-releasing hormone [GnRH] agonists or antagonists), which can be continued while participants are receiving protocol therapy. Use of enzalutamide or apalutamide is permitted after completion of chemotherapy and must be held during chemotherapy for participants receiving prior to enrollment. Use of darolutamide is permitted during chemotherapy. Glucocorticoid-containing regimens, including abiraterone, are not permitted.
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Participants must be >= 18 years of age
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Participants must have a Zubrod performance status of =< 2 within 28 days prior to registration
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Participants must have a complete medical history and physical exam within 28 days prior to registration
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Absolute neutrophil count (ANC) >= 1.5 x 10^9 /L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
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Hemoglobin >= 9.0 g/dl (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
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Platelet count >= 100 x 10^9/L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
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Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
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Serum total bilirubin =< 1.5 x ULN (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
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Adequate renal function as defined by any 1 of the following: 1) Measured creatinine clearance (CL) > 50 mL/min OR 2) Calculated creatinine CL > 50 mL/min by the Cockcroft-Gault formula OR by 24-hour urine collection for determination of creatinine clearance (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
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Participants must not have uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) within 14 days prior to registration. Participants who have asymptomatic hypercalcemia are eligible provided that medical therapy to treat the hypercalcemia is planned
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Participants must not have a diagnosis of immunodeficiency nor be receiving systemic steroid therapy (equivalent of > 20 mg of hydrocortisone per day) or any other form of immunosuppressive therapy within 14 days prior to registration
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Participants must not have active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions:
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Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
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Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
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Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
- Rash must cover < 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency topical corticosteroids
- No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
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Participants must not have history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
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Participants must not have significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease, myocardial infarction within 3 months prior to registration, unstable arrythmias, or unstable angina
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Participants must not have had a major surgical procedure other than for diagnosis within 28 days prior to registration. Participant must not plan to receive a major surgical procedure during the course of protocol treatment. NOTE: Patient port placement is not considered a major surgery
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Participants must not have severe infections (i.e., Common Terminology Criteria for Adverse Events [CTCAE] grade >= 2) at time of registration, including but not limited to hospitalization for complications for infection, bacteremia, or severe pneumonia
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Participants must not have known active tuberculosis
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Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load, with testing performed as clinically indicated
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Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV viral load, with testing performed as clinically indicated
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Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load within 6 months of registration
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Participants must not have prior allogeneic bone marrow transplantation or solid organ transplant
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Participants must not have received administration of a live, attenuated vaccine (e.g., FluMist [registered trademark]) within 28 days prior to initiation of study treatment, during treatment with atezolizumab, and not plan to receive for 5 months after the last dose of atezolizumab
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Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method (with details provided as a part of the consent process) during the treatment period and for 5 months after the final dose of atezolizumab. 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 sideeffect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
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Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
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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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (atezolizumab, platinum drug, etoposide) Biospecimen Collection During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. During maintenance phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm I (atezolizumab, platinum drug, etoposide) Computed Tomography During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. During maintenance phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm I (atezolizumab, platinum drug, etoposide) Etoposide During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. During maintenance phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm I (atezolizumab, platinum drug, etoposide) Magnetic Resonance Imaging During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. During maintenance phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm II (atezolizumab, platinum drug, etoposide, observation) Atezolizumab During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm II (atezolizumab, platinum drug, etoposide, observation) Biospecimen Collection During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm II (atezolizumab, platinum drug, etoposide, observation) Carboplatin During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm II (atezolizumab, platinum drug, etoposide, observation) Computed Tomography During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm II (atezolizumab, platinum drug, etoposide, observation) Magnetic Resonance Imaging During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm II (atezolizumab, platinum drug, etoposide, observation) Patient Observation During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm III (platinum drug, etoposide, observation) Biospecimen Collection During induction phase, patients receive carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm III (platinum drug, etoposide, observation) Computed Tomography During induction phase, patients receive carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm III (platinum drug, etoposide, observation) Etoposide During induction phase, patients receive carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm III (platinum drug, etoposide, observation) Magnetic Resonance Imaging During induction phase, patients receive carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm III (platinum drug, etoposide, observation) Patient Observation During induction phase, patients receive carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm I (atezolizumab, platinum drug, etoposide) Atezolizumab During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. During maintenance phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm I (atezolizumab, platinum drug, etoposide) Carboplatin During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. During maintenance phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm I (atezolizumab, platinum drug, etoposide) Cisplatin During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. During maintenance phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm II (atezolizumab, platinum drug, etoposide, observation) Cisplatin During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm II (atezolizumab, platinum drug, etoposide, observation) Etoposide During induction phase, patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle, carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle, and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm III (platinum drug, etoposide, observation) Carboplatin During induction phase, patients receive carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study. Arm III (platinum drug, etoposide, observation) Cisplatin During induction phase, patients receive carboplatin IV over 30 minutes or cisplatin IV over 60 minutes on day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo observation for 1 year. Patients also undergo CT scan and/or MRI throughout the trial and blood sample collection on study.
- Primary Outcome Measures
Name Time Method Overall survival From date of registration or from date of start of observation/maintenance therapy to date of death due to any cause, assessed up to 5 years Log-rank tests stratified by the randomization stratification factors will be used for null hypothesis (efficacy) tests. Cox regression models stratified by the randomization stratification factors will be used for alternative hypothesis (futility) tests.
- Secondary Outcome Measures
Name Time Method Progression-free survival From date of registration or start of observation/maintenance therapy to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 5 years Will be estimated using the Kaplan-Meier method and compared using log-rank tests.
Objective response rate (confirmed complete response [CR] or partial response [PR]) Up to 5 years from study enrollment Will be tabulated and compared between arms using Fisher's exact test.
Clinical benefit rate (confirmed CR or PR of any amount of time or stable disease for 6 months or longer) Up to 5 years from study enrollment Will be tabulated and compared between arms using Fisher's exact test.
Duration of response Time from date of initial response to date of progression or death, assessed up to 5 years Will be estimated non-parametrically using cumulative incidence curves.
Trial Locations
- Locations (215)
Alaska Women's Cancer Care
🇺🇸Anchorage, Alaska, United States
Cancer Center at Saint Joseph's
🇺🇸Phoenix, Arizona, United States
Mayo Clinic Hospital in Arizona
🇺🇸Phoenix, Arizona, United States
Kaiser Permanente-Anaheim
🇺🇸Anaheim, California, United States
Sutter Auburn Faith Hospital
🇺🇸Auburn, California, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
🇺🇸Auburn, California, United States
Kaiser Permanente-Baldwin Park
🇺🇸Baldwin Park, California, United States
Kaiser Permanente-Bellflower
🇺🇸Bellflower, California, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸Berkeley, California, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
🇺🇸Cameron Park, California, United States
Mercy Cancer Center - Carmichael
🇺🇸Carmichael, California, United States
Mercy San Juan Medical Center
🇺🇸Carmichael, California, United States
Mercy Cancer Center - Elk Grove
🇺🇸Elk Grove, California, United States
Kaiser Permanente-Fontana
🇺🇸Fontana, California, United States
Palo Alto Medical Foundation-Fremont
🇺🇸Fremont, California, United States
Kaiser Permanente South Bay
🇺🇸Harbor City, California, United States
Kaiser Permanente-Irvine
🇺🇸Irvine, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Kaiser Permanente West Los Angeles
🇺🇸Los Angeles, California, United States
Memorial Medical Center
🇺🇸Modesto, California, United States
Palo Alto Medical Foundation-Camino Division
🇺🇸Mountain View, California, United States
Kaiser Permanente-Ontario
🇺🇸Ontario, California, United States
Palo Alto Medical Foundation Health Care
🇺🇸Palo Alto, California, United States
Kaiser Permanente - Panorama City
🇺🇸Panorama City, California, United States
Kaiser Permanente-Riverside
🇺🇸Riverside, California, United States
Mercy Cancer Center - Rocklin
🇺🇸Rocklin, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
🇺🇸Roseville, California, United States
Sutter Roseville Medical Center
🇺🇸Roseville, California, United States
Mercy Cancer Center - Sacramento
🇺🇸Sacramento, California, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
Kaiser Permanente-San Diego Zion
🇺🇸San Diego, California, United States
California Pacific Medical Center-Pacific Campus
🇺🇸San Francisco, California, United States
Kaiser Permanente-San Marcos
🇺🇸San Marcos, California, United States
Palo Alto Medical Foundation-Santa Cruz
🇺🇸Santa Cruz, California, United States
Sutter Pacific Medical Foundation
🇺🇸Santa Rosa, California, United States
Palo Alto Medical Foundation-Sunnyvale
🇺🇸Sunnyvale, California, United States
Sutter Solano Medical Center/Cancer Center
🇺🇸Vallejo, California, United States
Kaiser Permanente-Woodland Hills
🇺🇸Woodland Hills, California, United States
Woodland Memorial Hospital
🇺🇸Woodland, California, United States
AdventHealth Porter
🇺🇸Denver, Colorado, United States
AdventHealth Parker
🇺🇸Parker, 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
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Hawaii Cancer Care - Westridge
🇺🇸'Aiea, Hawaii, United States
Pali Momi Medical Center
🇺🇸'Aiea, Hawaii, United States
The Queen's Medical Center - West Oahu
🇺🇸'Ewa Beach, Hawaii, United States
Hawaii Cancer Care Inc - Waterfront Plaza
🇺🇸Honolulu, Hawaii, United States
Queen's Cancer Cenrer - POB I
🇺🇸Honolulu, Hawaii, United States
Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
Straub Clinic and Hospital
🇺🇸Honolulu, Hawaii, United States
Queen's Cancer Center - Kuakini
🇺🇸Honolulu, Hawaii, United States
Centralia Oncology Clinic
🇺🇸Centralia, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, 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
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, 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
Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Northwestern Medicine Lake Forest Hospital
🇺🇸Lake Forest, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
🇺🇸New Lenox, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Northwestern Medicine Orland Park
🇺🇸Orland Park, Illinois, United States
University of Chicago Medicine-Orland Park
🇺🇸Orland Park, Illinois, United States
UW Health Carbone Cancer Center Rockford
🇺🇸Rockford, 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
Mary Greeley Medical Center
🇺🇸Ames, Iowa, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
🇺🇸Ankeny, Iowa, United States
McFarland Clinic - Boone
🇺🇸Boone, Iowa, United States
Saint Anthony Regional Hospital
🇺🇸Carroll, Iowa, United States
Mercy Cancer Center-West Lakes
🇺🇸Clive, Iowa, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
🇺🇸Clive, Iowa, United States
Greater Regional Medical Center
🇺🇸Creston, 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
McFarland Clinic - Trinity Cancer Center
🇺🇸Fort Dodge, Iowa, United States
McFarland Clinic - Jefferson
🇺🇸Jefferson, Iowa, United States
McFarland Clinic - Marshalltown
🇺🇸Marshalltown, Iowa, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
🇺🇸Waukee, Iowa, United States
Mercy Medical Center-West Lakes
🇺🇸West Des Moines, Iowa, United States
LSU Health Baton Rouge-North Clinic
🇺🇸Baton Rouge, Louisiana, United States
Our Lady of the Lake Physician Group
🇺🇸Baton Rouge, Louisiana, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, 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
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
🇺🇸Brighton, Michigan, United States
Trinity Health Medical Center - Brighton
🇺🇸Brighton, Michigan, United States
Henry Ford Cancer Institute-Downriver
🇺🇸Brownstown, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
🇺🇸Canton, Michigan, United States
Trinity Health Medical Center - Canton
🇺🇸Canton, 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
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
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
🇺🇸Grand Rapids, Michigan, United States
Trinity Health Grand Rapids Hospital
🇺🇸Grand Rapids, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Karmanos Cancer Institute at McLaren Greater Lansing
🇺🇸Lansing, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸Livonia, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸Muskegon, Michigan, United States
Corewell Health Lakeland Hospitals - Niles Hospital
🇺🇸Niles, Michigan, United States
Cancer and Hematology Centers of Western Michigan - Norton Shores
🇺🇸Norton Shores, Michigan, United States
Henry Ford Medical Center-Columbus
🇺🇸Novi, Michigan, United States
Corewell Health Reed City Hospital
🇺🇸Reed City, Michigan, United States
Corewell Health William Beaumont University Hospital
🇺🇸Royal Oak, Michigan, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
🇺🇸Saint Joseph, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Corewell Health Beaumont Troy Hospital
🇺🇸Troy, Michigan, United States
Henry Ford Health Warren Hospital
🇺🇸Warren, Michigan, United States
Henry Ford West Bloomfield Hospital
🇺🇸West Bloomfield, Michigan, United States
University of Michigan Health - West
🇺🇸Wyoming, Michigan, United States
Huron Gastroenterology PC
🇺🇸Ypsilanti, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
🇺🇸Ypsilanti, Michigan, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
Saint Luke's Hospital of Duluth
🇺🇸Duluth, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Mercy Hospital Joplin
🇺🇸Joplin, Missouri, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Saint Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸Lebanon, New Hampshire, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Duke Cancer Center Cary
🇺🇸Cary, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Levine Cancer Institute-SouthPark
🇺🇸Charlotte, North Carolina, United States
Atrium Health University City/LCI-University
🇺🇸Charlotte, North Carolina, United States
Levine Cancer Institute-Ballantyne
🇺🇸Charlotte, North Carolina, United States
Southeastern Medical Oncology Center-Clinton
🇺🇸Clinton, North Carolina, United States
Atrium Health Cabarrus/LCI-Concord
🇺🇸Concord, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Levine Cancer Institute-Gaston
🇺🇸Gastonia, North Carolina, United States
Southeastern Medical Oncology Center-Goldsboro
🇺🇸Goldsboro, North Carolina, United States
Southeastern Medical Oncology Center-Jacksonville
🇺🇸Jacksonville, North Carolina, United States
FirstHealth of the Carolinas-Moore Regional Hospital
🇺🇸Pinehurst, North Carolina, United States
Duke Cancer Center Raleigh
🇺🇸Raleigh, North Carolina, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Toledo Clinic Cancer Centers-Toledo
🇺🇸Toledo, Ohio, United States
Cancer Centers of Southwest Oklahoma Research
🇺🇸Lawton, Oklahoma, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Providence Cancer Institute Clackamas Clinic
🇺🇸Clackamas, Oregon, United States
Providence Newberg Medical Center
🇺🇸Newberg, Oregon, United States
Providence Willamette Falls Medical Center
🇺🇸Oregon City, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
Smilow Cancer Hospital Care Center - Westerly
🇺🇸Westerly, Rhode Island, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Parkland Memorial Hospital
🇺🇸Dallas, Texas, United States
UT Southwestern Simmons Cancer Center - RedBird
🇺🇸Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Fort Worth
🇺🇸Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
Ben Taub General Hospital
🇺🇸Houston, Texas, United States
UT Southwestern Clinical Center at Richardson/Plano
🇺🇸Richardson, Texas, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
Dartmouth Cancer Center - North
🇺🇸Saint Johnsbury, Vermont, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
University of Washington Medical Center - Montlake
🇺🇸Seattle, Washington, United States
United Hospital Center
🇺🇸Bridgeport, West Virginia, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Marshfield Medical Center - Minocqua
🇺🇸Minocqua, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States