eoadjuvant chemotherapy with Atezolizumab or Placebo followed by adjuvant Atezolizumab or Placebo
- Conditions
- Patients with early breast cancerMedDRA version: 20.0 Level: LLT Classification code 10007050 Term: Cancer System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-002771-25-ES
- Lead Sponsor
- SABP Foundation Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 1520
1. The patient must have consented to participate. 2. The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy. 3. 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. 4.Central testing for ER, PgR, and HER2 will be performed, and the tumor must be determined to be ER-negative, PgR-negative, and HER2-negative by current ASCO/CAP Guidelines Recommendations. Formalin-fixed, paraffin-embedded (FFPE) breast tissue from core biopsy has therefore to be sent to the GBG central pathology laboratory prior to randomization for central confirmation of TNBC status and for correlative science studies. 5. The tumor specimen used for central ER, PgR, and HER2 testing must also be used for central testing of PD-L1 status using the Ventana PD-L1 (SP142) assay kit. Patients will be eligible irrespective of PD-L1 testing result including PD-L1 indeterminate. Patients will be classified as positive, negative, or indeterminate for stratification purposes. 6. Patients must be > or = 18 years old. 7. Patient may be female or male. 8. The ECOG performance status must be 0-1. 9. The 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. 10. Ipsilateral axillary lymph nodes must be evaluated by imaging (ultrasound, and/or MRI) within 42 days prior to study entry. If suspicious or abnormal, FNA or core biopsy is recommended. 11.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. 12. Blood counts performed within 28 days prior to randomization. 13. Evidence of adequate hepatic function performed within 28 days prior to randomization.
14.Patients with AST or ALT or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (CT, MRI, abdominal ultrasound, PET-CT, or PET scan) performed within 28 days prior to randomization does not demonstrate metastatic disease and the requirements in criterion 13 are met. 15. Patients with alkaline phosphatase that is > ULN but < or = 2.5 x ULN or with unexplained bone pain are eligible for inclusion in the study if bone imaging (bone scan, PET-CT scan, or PET scan) supported by additional studies when indicated (CT, x-ray, MRI) performed within 28 days prior to randomization does not demonstrate metastatic disease. 16.Patients with N2 or N3 nodal disease or T3 primary disease must undergo liver and bone imaging (as described in criteria 14 and 15) within 28 days prior to randomization. 17. Creatinine clearance > or = 50 mL/min performed within 28 days prior to randomization. 18.PT/INR < or = ULN within 28 days prior to randomization. For laboratories that do not report an ULN for the INR assay, use < or = 1.2 as the value for the ULN. Patients receiving therapeutic anti-coagulants are not eligible. 19.A serum TSH and AM (morning) cortisol performed within 28 days prior
- 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 or
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