eoadjuvant chemotherapy with Atezolizumab or Placebo followed by adjuvant Atezolizumab or Placebo
- Conditions
- Patients with early breast cancerMedDRA version: 20.0Level: LLTClassification code 10007050Term: CancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-002771-25-DE
- Lead Sponsor
- SABP Foundation Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1550
- Patient must have consented to participate and, prior to beginning specific study procedures, must have signed and dated an appropriate IEC-approved consent form.
- Diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy.
- Pretreatment research core biopsy of the primary tumor must be performed with submission of 2 cores for required correlative studies.
- Local testing on the diagnostic core must have determined the tumor to be ER-negative, PgR-negative, and HER2-negative by current ASCO/CAP guidelines.
- Central testing for ER, PgR, HER2 and Ki-67 will be performed, and the tumor must be determined to be ER-negative, PgR-negative, and HER2-negative by current ASCO/CAP Guidelines Recommendations. Stromal TILs wil be evaluated in three groups: low immune infiltrate (0-10% stromal TILs), intermediate immune infiltrate(11-59% stromal TILs), LPBC (060-100% stromal TILs. Material from either the diagnostic core biopsy or the research biopsy can be used for central testing depending on local preferences and standards.
- Tumor specimen must also be used for central testing of PD-L1 Status.
- Patients must be >= 18 years old.
- ECOG performance status must be 0-1
- Primary tumor can be clinical stage T2 or T3, if clinically node negative according to AJCC 7th Edition. If the regional lymph nodes are cN1 and cytologically or histologically positive or cN2–N3 with or without a biopsy, the primary breast tumor can be clinically T1c, T2, or T3.
- Ipsilateral axillary lymph nodes must be evaluated by imaging (mammogram, ultrasound, and/or MRI) within 84 days prior to study entry. If suspicious or abnormal, FNA or core biopsy is recommended. Findings of these evaluations will be used to define the nodal status prior to study entry according to the following criteria:
•Nodal status – negative
?Imaging of the axilla is negative;
?Imaging is suspicious or abnormal but the FNA or core biopsy of the questionable node(s) on imaging is negative;
•Nodal status – positive
?FNA or core biopsy of the node(s) is cytologically or histologically suspicious or positive.
?Imaging is suspicious or abnormal but FNA or core biopsy was not performed.
- Patients with synchronous bilateral or multicentric HER2-negative breast cancer are eligible as long as the highest risk tumor is ER-negative and PgR-negative and meets stage eligibility criteria. All of the other invasive tumors must also be HER2-negative by ASCO/CAP Guidelines based on local testing. Central testing to confirm TNBC status is only required for the highest risk tumor.
- Blood counts performed within 28 days prior to randomization must meet the following criteria:
•ANC must be ? 2000/mm3
•platelet count must be 100,000/mm3
•hemoglobin must be 10 g/dL
- The following criteria for evidence of adequate hepatic function performed within
28 days prior to randomization must be met:
•total bilirubin must be ULN for the lab unless the patient has a bilirubin elevation
? ULN to 1.5 x ULN due to Gilbert’s disease or similar syndrome involving slow conjugation of bilirubin; and
•alkaline phosphatase must be 2.5 x ULN for the lab
•AST and ALT must be 1.5 x ULN for the lab
- Patients with AST or ALT or alkaline phosphatase ULN are eligible for inclusion in the study if liver imaging (CT, MRI, PET-CT, or PET scan) performed within 28 days prior to randomization does not demonstrate metastatic disease and the requirements in criterion above are m
- Excisional biopsy or lumpectomy performed prior to study entry.
- FNA alone to diagnose the breast cancer.
- Surgical axillary staging procedure prior to randomization. Exception: FNA or core biopsy of an axillary node is permitted for any patient. A pre-neoadjuvant therapy sentinel lymph node biopsy for patients with clinically negative axillary nodes is prohibited.
- Definitive clinical or radiologic evidence of metastatic disease.
- Previous history of contralateral invasive breast cancer. (Patients with synchronous and/or previous contralateral DCIS or LCIS are eligible.)
- Previous history of ipsilateral invasive breast cancer or ipsilateral DCIS. (Patients with synchronous or previous ipsilateral LCIS are eligible.)
- History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry.
- Treatment including radiation therapy, chemotherapy, or targeted therapy, for the currently diagnosed breast cancer prior to randomization.
- Previous therapy with anthracyclines or taxanes for any malignancy.
- Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens.
- Uncontrolled hypertension defined as sustained systolic BP 150 mmHg or diastolic BP 90 mmHg. Patients requiring 3 BP medications are not eligible.
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells.
- Known allergy or hypersensitivity to the components of the atezolizumab formulation.
- Known allergy or hypersensitivity to the components of the doxorubicin, cyclophosphamide, carboplatin, or paclitaxel formulations.
- Known allergy or hypersensitivity to liposomal or pegylated G-CSF formulations.
- Active or history of autoimmune disease or immune deficiency.
- 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.
- Patients known to be HIV positive.
- Active hepatitis B virus (HBV) infection, defined as having a positive hepatitis B surface antigen (HBsAg) test at screening.
Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening, are eligible for the study if active HBV infection is ruled out on the basis of HBV DNA viral load per local guidelines.
- Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test at screening confirmed by a polymerase chain reaction (PCR) positive for HCV RNA.
- Patients with clinically active tuberculosis.
- Severe infection within 28 days prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
- Prior allogeneic stem cell or solid organ transplantation.
- Patients receiving therapeutic anti-coagulants are not eligible.
- Administration of a live, attenuated vaccine within 28 days prior to randomization or anticipation that such vaccine will be required during the study. Patients must agree not to receive live, attenuated influenza vaccine within 28 days prior to randomization, during treatment or within 5 months following
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method