Clinical Trial of Neoadjuvant Chemotherapy With Atezolizumab or Placebo in Patients With Triple-Negative Breast Cancer Followed After Surgery by Atezolizumab or Placebo

Running, not enrolling · Phase 3 · Has a placebo group

Conditions studied: Triple Negative Breast Cancer

In brief

The main purpose of this study is to learn if the usual chemotherapy given before surgery (neoadjuvant therapy) for breast cancer plus the experimental drug, atezolizumab, is better than the usual chemotherapy plus a placebo. (A placebo is a drug that looks like the study drug but contains no medication.) The usual chemotherapy in this study is paclitaxel (WP) and carboplatin followed by doxorubicin and cyclophosphamide (AC) or epirubicin and cyclophosphamide (EC). Usually, after neoadjuvant therapy and surgery for triple negative breast cancer, no additional treatment is given unless the cancer returns. This study will also look at continuing treatment after surgery with atezolizumab or the placebo. To be better, atezolizumab given with the neoadjuvant therapy should be better at: 1) decreasing the amount of tumor in the breast than the placebo given with the usual chemotherapy and 2) decreasing the chance of the cancer from returning after surgery. Another purpose of this study is to test the good and bad effects of atezolizumab when added to the usual chemotherapy. Atezolizumab may keep your cancer from growing but it can also cause side effects.

Key facts

Study ID

NCT03281954

Run by

NSABP Foundation Inc

People needed

1550

Starts

2017-12-19

Expected to finish

2027-11-30

Last updated by the study team

2024-04-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• The patient must have consented to participate and, prior to beginning specific study procedures, must have signed and dated an appropriate IRB-approved consent form that conforms to federal and institutional guidelines for study treatment and for submission of tumor samples from a research biospy as required by NSABP B-59/GBG 96-GeparDouze for baseline correlative science studies.
• The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy.
• 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. (If local testing has determined a tumor to be HER2 equivocal or to have a borderline ER/PgR status (% IHC staining < 10% for both) and other eligibility criteria are met, material may be submitted for central testing to determine eligibility.)
• 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.
• 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 testing result including PD-L1 indeterminate Patients will be classifies as positive, negative, or indeterminate for stratification purposes.
• Patients must be ≥ 18 years old.
• Patient may be female or male.
• The ECOG performance status must be 0-1.
• 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.
• 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 ≥ 1500/mm3;
• platelet count must be ≥ 100,000/mm3; and
• 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; and
• 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, abdominal ultrasound, PET-CT, or PET scan) performed within 28 days prior to randomization does not demonstrate metastatic disease and the requirements in criterion (just above) are met.
• Patients with alkaline phosphatase that is > ULN but less than or equal to 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.
• Patients with N2 or N3 nodal disease or T3 primary disease must undergo liver and bone imaging (as described in 4.1.13 and 4.1.14) within 28 days prior to randomization, irrespective of baseline lab results, and studies must not demonstrate metastatic disease. Chest imaging with chest x-ray PA and Lateral, CT of the chest, or PET-CT must also be performed.
• Creatinine clearance ≥ 50 mL/min (see Section 7.2.1 for instructions regarding calculation of creatinine clearance) performed within 28 days prior to randomization.

You may not qualify if…

• 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. This includes but is not confined to:
• Active cardiac disease: angina pectoris that requires the use of anti-anginal medication; ventricular arrhythmias except for benign premature ventricular contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; conduction abnormality requiring a pacemaker; valvular disease with documented compromise in cardiac function; or symptomatic pericarditis.
• History of cardiac disease: myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular function within 6 months prior to randomization; history of documented CHF; or documented cardiomyopathy.
• Uncontrolled hypertension defined as sustained systolic BP > 150 mmHg or diastolic BP > 90 mmHg. (Patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria.) 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, epirubicin, 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, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis for a more comprehensive list of autoimmune diseases and immune deficiencies) with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
• Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are permitted 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.
• 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.

Where it is running

• Katmai Oncology Group — Anchorage, Alaska, United States
• St. Bernard's Medical Center — Jonesboro, Arkansas, United States
• St. Bernard's Medical Center — Paragould, Arkansas, United States
• Kaiser Permanente-Anaheim — Anaheim, California, United States
• Kaiser Permanente-Baldwin Park — Baldwin Park, California, United States
• Kaiser Permanente-Bellflower — Bellflower, California, United States
• Arrowhead Regional Medical Center — Colton, California, United States
• City of Hope — Duarte, California, United States
• Kaiser Permanente-Fontana — Fontana, California, United States
• Kaiser Permanente-Harbor City — Harbor City, California, United States
• Kaiser Permanente-Irvine — Irvine, California, United States
• Cancer and Blood Specialty Clinic — Los Alamitos, California, United States
• Kaiser Permanente-Sunset — Los Angeles, California, United States
• Kaiser Permanente-West Los Angeles — Los Angeles, California, United States
• Kaiser Permanente-Panorama City — Panorama City, California, United States
• Kaiser Permanente-Riverside — Riverside, California, United States
• Kaiser Permanente Medical Group — San Diego, California, United States
• Kaiser Permanente-Zion — San Diego, California, United States
• Kaiser Permanente - Otay — San Diego, California, United States
• Kaiser Permanente- San Marcos — San Marcos, California, United States
• City of Hope - South Pasadena — South Pasadena, California, United States
• Torrance Memorial Physician Network — Torrance, California, United States
• City of Hope - Upland — Upland, California, United States
• PIH Health — Whittier, California, United States
• University of South Alabama Mitchell Cancer Institute — Mobile, Alabama, United States

Full record on ClinicalTrials.gov

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