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

• ClinicalTrials.gov Identifier: NCT03281954
• Recruitment Status: Active, not recruiting
• First Posted: September 13, 2017
• Last Update Posted: March 7, 2023
• Sponsor: NSABP Foundation Inc
• Collaborators: Genentech, Inc.; Hoffmann-La Roche
• Information provided by (Responsible Party): NSABP Foundation Inc

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Triple Negative Breast Cancer	Drug: Placebo; Drug: Atezolizumab	Phase 3

Detailed Description:

NSABP B-59/GBG 96-GeparDouze is a prospective, randomized, double-blind, Phase III clinical trial. This is a collaborative study being conducted by NSABP Foundation, Inc. in partnership with the German Breast Group (GBG), and supported by funding by Genentech, a Member of the Roche Group, and F. Hoffmann-La Roche, Ltd.

In this clinical trial of neoadjuvant and adjuvant administration of atezolizumab/placebo in patients with high risk triple-negative breast cancer, the potential incremental efficacy and safety of neoadjuvant administration of atezolizumab/placebo with a sequential regimen of weekly paclitaxel with every-3-week carboplatin followed immediately by neoadjuvant administration of atezolizumab/placebo with AC/EC will be evaluated. Patients will then undergo surgery. Following recovery from surgery, patients will initiate approximately 6 months of adjuvant therapy with atezolizumab/placebo and receive the same investigational agent they received pre-operatively. Administration of radiation therapy will be based on local standards at the discretion of patients and investigators, but if administered, atezolizumab/placebo will be administered concurrently. Adjuvant atezolizumab/placebo may be delayed until after completion of radiation therapy per investigator discretion. Patients with residual invasive cancer at the time of surgery may receive capecitabine concurrently with atezolizumab/placebo in the adjuvant setting per investigator discretion and local guidelines. Patients with germline BRCA1 or BRCA2 mutations with residual invasive cancer at the time of surgery may receive olaparib in the adjuvant setting per investigator discretion and local guidelines. Patients receiving olaparib must discontinue atezolizumab/placebo.

The primary aims of the study are 1) to determine value of atezolizumab in improving pathologic complete response in the breast and post-therapy lymph nodes evaluated histologically (pCR breast and nodes [(ypT0/Tis ypN0)]), and 2) to determine the value of atezolizumab in improving event-free survival (EFS). Secondary aims include: pathologic complete response in the breast (ypT0/Tis); pathologic complete response in the breast and lymph nodes (ypT0 ypN0); positive nodal status conversion rate; overall survival; recurrence-free interval: distant disease-free survival; brain metastases free survival; and toxicity. The stratification factors for the study are: 1) clinical size of the primary tumor (1.1-3.0 cm; > 3.0 cm); 2) nodal status as determined by protocol-specified criteria (negative, positive); 3) AC/EC (every 2 weeks; every 3 weeks); and 4) Region (North America; Europe).

For patient eligibility, local testing on the diagnostic core must have determined the patient's tumor to be ER-negative, PgR-negative, and HER2-negative by current ASCO/CAP guidelines. Material from either the diagnostic core biopsy or the research biopsy must be sent for central testing for confirmation of ER, PgR, and HER2 to confirm eligibility. If local testing has determined a tumor to be HER2 equivocal or to have a borderline ER/PgR status (% IHC staining < 10% for both), material may be submitted for central testing to determine eligibility.

In order to proactively identify and further assess any cardiac toxicity that may occur with the combination of anthracyclines and atezolizumab, this study includes a cardiac safety lead-in for the first 60 patients who initiate AC/EC. The safety lead-in will consist of assessment of ECG and serum troponin-T obtained just prior to administration of the first dose of AC/EC, following completion of the administration of the 1st and 3rd cycle of AC/EC prior to initiation of the atezolizumab/placebo. An additional assessment of LVEF with echocardiogram or MUGA scan will also be obtained prior to the 3rd dose of AC/EC. In order to provide an early assessment of cardiac safety, results of the troponin-T assessments, ECGs, LVEF assessment, and cardiac safety data will be evaluated by the Data Safety Monitoring Board (DSMB) when the last of the initial 20 patients who initiate AC/EC undergo their scheduled post-surgery LVEF assessment. When the last of the first 60 patients to initiate AC/EC undergo their scheduled post-surgery LVEF assessment, results of the troponin assessments, ECGs, LVEF assessments, and cardiac safety data from all 60 patients will be evaluated by the DSMB.

Research core biopsies of breast primary at baseline and 1-4 days prior to the second dose of atezolizumab/placebo are a study requirement for all patients. One to three representative blocks of residual primary tumor containing the maximum amount of tumor and node with the largest focus of metastasis is required from the definitive breast surgery if gross residual disease is greater than or equal to 1.0 cm. If gross residual disease is less than 1.0 cm, tissue should be submitted, if possible. Blood specimens will be collected on all patients at baseline for exploratory biomarker analysis and to support future correlative studies.

Accrual to NSABP B-59/GBG 96-GeparDouze began in December 2017 and was completed in May 2021 with a total of 1550 patients randomized. Based on actual accrual and the decision to eliminate pCR as a co-primary endpoint, we recalculated the power to detect a hazard ratio of 0.70 attributed to the addition of atezolizumab, assuming a lost-to-follow-up rate of 0.00083 per month, using the actual accrual pattern for the power calculation. With 1550 patients accrued in 42 months, an additional 22 months follow up will allow us to obtain 252 events under the assumptions stated above, which will provide 80% power to detect a HR of 0.7 between the atezolizumab and the placebo arm at an overall 2-sided alpha level of 0.05.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1550 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Phase III Clinical Trial of Neoadjuvant Chemotherapy With Atezolizumab or Placebo in Patients With Triple-Negative Breast Cancer Followed by Adjuvant Continuation of Atezolizumab or Placebo
• Actual Study Start Date: December 19, 2017
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: June 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; IV infusion once every 3 weeks for 4 doses (Cycle 1), once every 3 weeks for 4 doses (Cycle 2) and once every 3 weeks after surgery for 1 year after first dose	Drug: Placebo; Following randomization, patients will receive Paclitaxel 80 mg/m2 IV weekly x 12 doses + Carboplatin AUC of 5 IV Day 1 every 3 weeks for 4 cycles + placebo IV Day 1 every 3 weeks for 4 doses. Followed 2-3 weeks later by Doxorubicin (A) 60 mg/m2 IV + cyclophosphamide (C) 600 mg/m2 IV Day 1 every 2 or 3 weeks for 4 cycles OR Epirubicin (E) 90 mg/m2 IV + cyclophosphamide (C) 600 mg/m2 IV Day 1 every 2 or 3 weeks for 4 cycles. + placebo IV Day 1 every 3 weeks for 3 to 4 doses depending on AC/EC schedule used. Approximately 3-4 weeks later: Surgery (Lumpectomy or mastectomy and axillary staging), followed by placebo IV Day 1 every 3 weeks after surgery until 1 year after the first dose.
Experimental: Atezolizumab; IV infusion, 1200mg, once every 3 weeks for 4 doses (Cycle 1), once every 3 weeks for 4 doses (Cycle 2) and once every 3 weeks after surgery for 1 year after first dose	Drug: Atezolizumab; Following randomization, patients will receive Paclitaxel 80 mg/m2 IV weekly x 12 doses + Carboplatin AUC of 5 IV Day 1 every 3 weeks for 4 cycles + Atezolizumab 1200 mg Day 1 every 3 weeks for 4 doses. Followed 2-3 weeks later by Doxorubicin (A) 60 mg/m2 IV + cyclophosphamide (C) 600 mg/m2 IV Day 1 every 2 or 3 weeks for 4 cycles OR Epirubicin (E) 90 mg/m2 IV + cyclophosphamide (C) 600 mg/m2 IV Day 1 every 2 or 3 weeks for 4 cycles. + Atezolizumab 1200 mg Day 1 every 3 weeks for 3 to 4 doses depending on AC/EC schedule used. Approximately 3-4 weeks later: Surgery (Lumpectomy or mastectomy and axillary staging), followed by Atezolizumab 1200 mg Day 1 every 3 weeks after surgery until 1 year after the first dose.

Outcome Measures

Primary Outcome Measures :

1. Event-free survival (EFS) [ Time Frame: From randomization until event, through study follow up to the time target number of events is obtained, up to 5 years ]
   Time from randomization until event

Secondary Outcome Measures :

1. Overall survival (OS) [ Time Frame: From date of randomization through study follow-up, to the time the target number of events is obtained, up to 5 years ]
   Time from randomization until death from any cause
2. Pathologic complete response in the breast and lymph nodes (ypT0/Tis ypN0) [ Time Frame: Following completion of neoadjuvant therapy (ypT0/Tis ypN0) ]
   Absence of any invasive component in the resected breast specimen and all resected lymph nodes
3. Distant disease-free survival (DDFS) [ Time Frame: From date of randomization through study follow-up, to the time the target number of events is obtained, up to 5 years ]
   Time from randomization until distant recurrence, death from breast cancer, death from other causes, and second primary invasive cancer (non-breast)
4. Disease-free survival (DFS) [ Time Frame: From the first breast surgical procedure to the first disease recurrence or death from any cause ]
   Ipsilateral invasive breast tumor recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, ipsilateral or contralateral DCIS, second primary non-breast invasive cancer and death attributable to any cause including breast cancer, non-breast cancer, or unknown cause.
5. Frequency of Adverse Events [ Time Frame: From beginning of study therapy to 90 days after last dose of study therapy ]
   Frequency of adverse events graded according to the NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)
6. Frequency of immune Adverse Events of Special Interest [ Time Frame: From beginning of study therapy to 90 days after last dose of study therapy ]
   Frequency of immune adverse events of special interest according to the NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)
7. Cardiac safety lead-in (Troponin-T) [ Time Frame: prior to initial dose of AC/EC following completion of carboplatin/paclitaxel co-administered with atezolizumab/placebo, approximately 12 weeks ]
   Troponin-T levels in blood prior to initial dose of AC/EC following completion of carboplatin/paclitaxel co-administered with atezolizumab/placebo
8. Cardiac safety lead-in (Troponin-T) [ Time Frame: After administration of the 1st dose of AC/EC prior to administration of atezolizumab/placebo, approximately 1 hour after beginning the 1st dose of AC/EC ]
   Troponin-T levels in blood after administration of the 1st cycle of AC/EC prior to administration of atezolizumab/placebo
9. Cardiac safety lead-in (Troponin-T) [ Time Frame: After administration of the 3rd dose (Cycle 3; each cycle is 21 days) of AC/EC prior to administration of atezolizumab/placebo, approximately 1 hour after beginning the 3rd dose of AC/EC ]
   Troponin-T levels in blood after administration of the 3rd cycle of AC/EC prior to administration of atezolizumab/placebo
10. Cardiac safety lead-in (Left ventricular ejection fraction; LVEF) [ Time Frame: Prior to initiation of carboplatin/paclitaxel and atezolizumab/placebo, at baseline ]
    LVEF levels measured at baseline prior to initiation of carboplatin/paclitaxel and atezolizumab/placebo
11. Cardiac safety lead-in (Left ventricular ejection fraction; LVEF) [ Time Frame: Prior to the 3rd cycle (each cycle is every 21 days) of AC/EC, approximately 6 weeks after initiation of AC/EC ]
    LVEF levels measured before 3rd cycle of AC/EC
12. Cardiac safety lead-in (Left ventricular ejection fraction; LVEF) [ Time Frame: Four to 6 weeks after surgery ]
    LVEF levels measured after surgery

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.
• PT/INR ≤ ULN within 28 days of randomization. Patients receiving therapeutic anti-coagulants are not eligible.
• A serum TSH and AM (morning) cortisol performed within 28 days prior to randomization to obtain a baseline value. Patients with abnormal TSH or AM cortisol baseline levels should be further evaluated and managed per institutional standards. Asymptomatic patients who require initiation or adjustment of medication or are followed without initiating treatment based on endocrinologist's recommendations are eligible.
• LVEF assessment must be performed within 42 days prior to randomization. (LVEF assessment performed by echocardiogram is preferred; however, MUGA scan may be substituted based on institutional preferences.) The LVEF must be ≥ 55% regardless of the cardiac imaging facility's lower limit of normal.

• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab/placebo or 12 months after the last dose of chemotherapy.

  • A woman is considered to be of childbearing potential if she is not postmenopausal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
  • Examples of contraceptive methods with a failure rate of < 1% per year include: bilateral tubal ligation; male partner sterilization; hormonal contraceptives that inhibit ovulation; hormone-releasing intrauterine devices; copper intrauterine devices.
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
• Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

• 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.
• 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.
• 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 (e.g., FluMist) within 28 days prior to randomization, during treatment or within 5 months following the last dose of atezolizumab/placebo.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
• Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
• Treatment with systemic immunosuppressive medications (including but not limited to interferons, IL-2) within 28 days or 5 half-lives of the drug, whichever is longer, prior to randomization.
• Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis [anti-TNF] factor agents) within 14 days prior to randomization or anticipation of need for systemic immunosuppressive medications during the study.
• Nervous system disorder (paresthesias, peripheral motor neuropathy, or peripheral sensory neuropathy) ≥ Grade 2, per the CTCAE v4.0.
• Symptomatic peripheral ischemia.
• Pregnancy or lactation at the time of randomization or intention to become pregnant during the study. (Note: Negative serum pregnancy test must be obtained within 14 days prior to randomization).
• Use of any investigational agent within 28 days prior to randomization.

Contacts and Locations

Locations

United States, Alabama

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, United States, 36604

United States, Alaska

Katmai Oncology Group

Anchorage, Alaska, United States, 99508

United States, Arkansas

St. Bernard's Medical Center

Jonesboro, Arkansas, United States, 72401

St. Bernard's Medical Center

Paragould, Arkansas, United States, 72450

United States, California

Kaiser Permanente-Anaheim

Anaheim, California, United States, 92806

Kaiser Permanente-Baldwin Park

Baldwin Park, California, United States, 91706

Kaiser Permanente-Bellflower

Bellflower, California, United States, 90706

Arrowhead Regional Medical Center

Colton, California, United States, 92324

City of Hope

Duarte, California, United States, 91010

Kaiser Permanente-Fontana

Fontana, California, United States, 92335

Kaiser Permanente-Harbor City

Harbor City, California, United States, 90710

Kaiser Permanente-Irvine

Irvine, California, United States, 92618

Cancer and Blood Specialty Clinic

Los Alamitos, California, United States, 90720

Kaiser Permanente-Sunset

Los Angeles, California, United States, 90027

Kaiser Permanente-West Los Angeles

Los Angeles, California, United States, 90034

Kaiser Permanente-Panorama City

Panorama City, California, United States, 91402

Kaiser Permanente-Riverside

Riverside, California, United States, 92505

Kaiser Permanente Medical Group

San Diego, California, United States, 92108

Kaiser Permanente-Zion

San Diego, California, United States, 92120

Kaiser Permanente - Otay

San Diego, California, United States, 92153

Kaiser Permanente- San Marcos

San Marcos, California, United States, 92078

City of Hope - South Pasadena

South Pasadena, California, United States, 91030

Torrance Memorial Physician Network

Torrance, California, United States, 90505

City of Hope - Upland

Upland, California, United States, 91786

PIH Health

Whittier, California, United States, 90602

Kaiser Permanente-Woodland Hills

Woodland Hills, California, United States, 91367

United States, Florida

Mount Sinai Comprehensive Cancer Center Aventura

Aventura, Florida, United States, 33180

Memorial Healthcare System Office of Human Research

Hollywood, Florida, United States, 33021

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States, 33140

UF Health Cancer Center at Orlando Health

Orlando, Florida, United States, 32806

United States, Georgia

Gwinnett Hospital System Center for Cancer Care

Duluth, Georgia, United States, 30096

Gwinnett Hospital System Center for Cancer Care

Lawrenceville, Georgia, United States, 30046

Gwinnett Hospital System Center for Cancer Care

Snellville, Georgia, United States, 30078

United States, Illinois

Illinois Cancer Care-Bloomington

Bloomington, Illinois, United States, 61704

Affiliated Oncologists

Chicago Ridge, Illinois, United States, 60415

John H. Stroger, Jr. Hospital of Cook County

Chicago, Illinois, United States, 60612

Rush University Medical Center

Chicago, Illinois, United States, 60612

Cancer Care Specialists of Central Illinois

Decatur, Illinois, United States, 62526

Decatur Memorial Hospital

Decatur, Illinois, United States, 62526

Crossroads Cancer Center

Effingham, Illinois, United States, 62401

Emhurst Memorial Nancy W. Knowles Cancer Center

Elmhurst, Illinois, United States, 60126

Illinois Cancer Care-Galesburg

Galesburg, Illinois, United States, 61401

Edward Cancer Center

Naperville, Illinois, United States, 60540

Illinois Cancer Care-Ottawa

Ottawa, Illinois, United States, 61350

Illinois Cancer Care PC

Peoria, Illinois, United States, 61615

Illinois Cancer Care-Peru

Peru, Illinois, United States, 61354

Edward Cancer Center Plainfield

Plainfield, Illinois, United States, 60585

Cancer Care Specialists of Central Illinois-Swansea

Swansea, Illinois, United States, 62226

United States, Indiana

Fort Wayne Medical Oncology and Hematology Inc (W. Jefferson Blvd)

Fort Wayne, Indiana, United States, 46804

Fort Wayne Medical Oncology and Hematology Inc (Parkview Plaza)

Fort Wayne, Indiana, United States, 46845

United States, Iowa

Mercy Medical Center Hall-Perrine Cancer Center

Cedar Rapids, Iowa, United States, 52403

United States, Kansas

Cancer Center of Kansas - Chanute

Chanute, Kansas, United States, 66720

Cancer Center of Kansas - Dodge City

Dodge City, Kansas, United States, 67801

Susan B. Allen Memorial Hosptial

El Dorado, Kansas, United States, 67042

Cancer Center at Mercy - W. Laurel

Independence, Kansas, United States, 67301

Kingman Community Hospital

Kingman, Kansas, United States, 67068

Southwest Medical Center

Liberal, Kansas, United States, 67901

McPherson Center for Health

McPherson, Kansas, United States, 67460

Newton Medical Center

Newton, Kansas, United States, 67114

Labette Health

Parsons, Kansas, United States, 67357

Pratt Regional Medical Center

Pratt, Kansas, United States, 67124

Cancer Center of Kansas - Salina

Salina, Kansas, United States, 67401

Cancer Center of Kansas - Wichita

Wichita, Kansas, United States, 67214

Cancer Center of Kansas

Wichita, Kansas, United States, 67214

Winfield Healthcare Center

Winfield, Kansas, United States, 67156

United States, Kentucky

Norton Cancer Institute-Downtown

Louisville, Kentucky, United States, 40202

Norton Cancer Institute-Norton Healthcare Pavilion

Louisville, Kentucky, United States, 40202

University of Louisville-James Graham Brown Cancer Center

Louisville, Kentucky, United States, 40202

Baptist Health Louisville; Consultants in Blood Disorders and Cancer

Louisville, Kentucky, United States, 40207

Norton Cancer Institute-St Matthews

Louisville, Kentucky, United States, 40207

Norton Cancer Institute-Brownsboro

Louisville, Kentucky, United States, 40241

United States, Louisiana

Ochsner Medical Center-Kenner

Kenner, Louisiana, United States, 70065

West Jefferson Medical Center Cancer Center

Marrero, Louisiana, United States, 70072

University Medical Center New Orleans

New Orleans, Louisiana, United States, 70112

Ochsner Medical Center

New Orleans, Louisiana, United States, 70121

United States, Maryland

Greater Baltimore Medical Center

Baltimore, Maryland, United States, 21204

Medstar Union Memorial Hospital

Baltimore, Maryland, United States, 21218

Harry and Jeanette Weinberg Cancer Center at Franklin Square

Baltimore, Maryland, United States, 21237

Maryland Oncology Hematology

Bethesda, Maryland, United States, 20817

Maryland Oncology - Hematology Brandywine

Brandywine, Maryland, United States, 20613

Maryland Oncology - Hematology PA

Columbia, Maryland, United States, 21044

Maryland Oncology - Hematology Frederick

Frederick, Maryland, United States, 21702

Meritus Center for Clinical Research

Hagerstown, Maryland, United States, 21742

Maryland Oncology - Hematology PA

Lanham, Maryland, United States, 20706

Maryland Oncology Hematology

Rockville, Maryland, United States, 20850

Capital Hematology Oncology Associates

Silver Spring, Maryland, United States, 20904

Holy Cross Hospital

Silver Spring, Maryland, United States, 20910

University of Maryland, St. Joseph Medical Center

Towson, Maryland, United States, 21204

Maryland Oncology Hematology

Wheaton, Maryland, United States, 20902

United States, Massachusetts

Berkshire Hematology Oncology Services at Berkshire Medical Center Cancer and Infusion Center

Pittsfield, Massachusetts, United States, 01201

United States, Michigan

Henry Ford Cancer Institute Brownstown

Brownstown, Michigan, United States, 48183

Henry Ford Cancer Institute Macomb Hospital

Clinton Township, Michigan, United States, 48038

Henry Ford Medical Center Fairlane

Dearborn, Michigan, United States, 48126

Henry Ford Hospital

Detroit, Michigan, United States, 48202

Michigan State University

East Lansing, Michigan, United States, 48823

Henry Ford Allegiance Health

Jackson, Michigan, United States, 49201

Michigan State University-Breslin Cancer Center

Lansing, Michigan, United States, 48910

Henry Ford Medical Center Columbus

Novi, Michigan, United States, 48377

Henry Ford Hospital W Bloomfield

West Bloomfield, Michigan, United States, 48322

Henry Ford Cancer Institute Wyandotte Hospital

Wyandotte, Michigan, United States, 48192

United States, Missouri

University of Missouri-Ellis Fischel Cancer Center

Columbia, Missouri, United States, 65212

United States, New Jersey

Newark Beth Israel Medical Center

Newark, New Jersey, United States, 07112

MD Anderson Cancer Center at Cooper

Voorhees, New Jersey, United States, 08043

United States, New York

New York Oncology Hematology PC

Albany, New York, United States, 12206

Broome Oncolgy

Binghamton, New York, United States, 13905

Broome Oncology

Johnson City, New York, United States, 13790

Health Quest Medical Practice

Poughkeepsie, New York, United States, 12601

Vassar Brothers Medical Center

Poughkeepsie, New York, United States, 12601

United States, North Carolina

RHOA of Cary

Cary, North Carolina, United States, 27518

Waverly Hematology Oncology

Cary, North Carolina, United States, 27518

Carolinas Medical Center-Levine Cancer Insitute

Charlotte, North Carolina, United States, 28204

Levine Cancer Center Institute Pineville

Charlotte, North Carolina, United States, 28210

RHOA of Garner

Garner, North Carolina, United States, 27529

UNC Regional Physicians Hematology and Oncolgoy

High Point, North Carolina, United States, 27262

FirstHealth of the Carolinas FirstHealth Outpatient Cancer Center

Pinehurst, North Carolina, United States, 28374

Rex Cancer Center

Raleigh, North Carolina, United States, 27607

RHOA of Blue Ridge

Raleigh, North Carolina, United States, 27607

RCC of Wakefield

Raleigh, North Carolina, United States, 27614

Nash UNC Health Care - Danny Talbott Cancer Center

Rocky Mount, North Carolina, United States, 28704

United States, North Dakota

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States, 58122

United States, Ohio

Aultman Alliance Cancer Center

Alliance, Ohio, United States, 44601

Aultman Hospital

Canton, Ohio, United States, 44710

Aultman Medical Group Hematology and Oncology

Canton, Ohio, United States, 44710

The Ohio State University Wexner Medical Center-Investigational Drug Service Oncology

Columbus, Ohio, United States, 43210

The Stephanie Speilman Comprehensive Breast Center

Columbus, Ohio, United States, 43212

United States, Oregon

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, United States, 97401

Kaiser Permanente Northwest-Oncology/Hematology

Portland, Oregon, United States, 97227

Northwest Cancer Specialists

Tigard, Oregon, United States, 97223

United States, Pennsylvania

UPMC Hillman Cancer Center-Beaver

Beaver, Pennsylvania, United States, 15009

UPMC Hillman Cancer Center - Passavant North

Cranberry Township, Pennsylvania, United States, 16066

Ephrata Cancer Center

Ephrata, Pennsylvania, United States, 17522

Allegheny Cancer Institute St. Vincent

Erie, Pennsylvania, United States, 16505

St. Vincent Hospital

Erie, Pennsylvania, United States, 16544

UPMC Cancer Center Horizon

Farrell, Pennsylvania, United States, 16121

Wellspan Medical Oncology

Gettysburg, Pennsylvania, United States, 17325

UPMC Hillman Cancer Center- Mountain View

Greensburg, Pennsylvania, United States, 15601

UPMC Cancer Center Greenville

Greenville, Pennsylvania, United States, 16125

AHN Cancer Institute at Jefferson

Jefferson Hills, Pennsylvania, United States, 15025

Seechler Family Cancer Center

Lebanon, Pennsylvania, United States, 17042

Forbes Regional Hospital

Monroeville, Pennsylvania, United States, 15146

UPMC Hillman Cancer Center UPMC East-Monroeville

Monroeville, Pennsylvania, United States, 15146

UPMC Hillman Cancer Center Norwin

N. Huntingdon, Pennsylvania, United States, 15642

UPMC Hillman Cancer Center New Castle

New Castle, Pennsylvania, United States, 16105

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States, 15212

WPAON at AGH

Pittsburgh, Pennsylvania, United States, 15212

WPAON at WPH

Pittsburgh, Pennsylvania, United States, 15212

Magee-Women's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15213

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States, 15224

UPCI Investigational Drug Services

Pittsburgh, Pennsylvania, United States, 15232

UPMC Hillman Cancer Center @ Passavant - HOA

Pittsburgh, Pennsylvania, United States, 15237

UPMC Hillman Cancer Center @ Passavant - OHA

Pittsburgh, Pennsylvania, United States, 15237

UPMC Hillman Cancer Center-Upper Saint Clair

Pittsburgh, Pennsylvania, United States, 15243

UPMC Cancer Center Northwest

Seneca, Pennsylvania, United States, 16346

UPMC Hillman Cancer Center - Uniontown

Uniontown, Pennsylvania, United States, 15401

UPMC Hillman Cancer Center-Washington

Washington, Pennsylvania, United States, 15301

Wexford Health & Wellness Pavilion

Wexford, Pennsylvania, United States, 15090

Cancer Care Associates of York

York, Pennsylvania, United States, 17403

Wellspan Health-York Cancer Center Oncology Research

York, Pennsylvania, United States, 17403

United States, Rhode Island

Women's and Infants Hospital

Providence, Rhode Island, United States, 02905

United States, South Carolina

Gibbs Cancer Center and Research Institute - Pelham

Greer, South Carolina, United States, 29651

Spartanburg Medical Center

Spartanburg, South Carolina, United States, 29303

United States, South Dakota

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, United States, 57104

Avera Cancer Institute-Sioux Falls

Sioux Falls, South Dakota, United States, 57105

Avera Cancer Institute

Sioux Falls, South Dakota, United States, 57105

United States, Tennessee

Wellmont Cancer Institute

Johnson City, Tennessee, United States, 37601

Wellmont Cancer Institute

Kingsport, Tennessee, United States, 37660

United States, Texas

Dell Seton Medical Center at the University of Texas-Seton Infusion Center

Austin, Texas, United States, 72701

Texas Oncology Bedford

Bedford, Texas, United States, 76022

Texas Oncology Carrollton

Carrollton, Texas, United States, 75010

Texas Oncology - Methodist Dallas Cancer Center

Dallas, Texas, United States, 75203

Texas Oncology - Medical City Dallas

Dallas, Texas, United States, 75230

Texas Oncology Dallas Presbyterian Hospital

Dallas, Texas, United States, 75231

Texas Oncology Denton

Denton, Texas, United States, 76201

Texas Oncology Flower Mound

Flower Mound, Texas, United States, 75028

Baylor College of Medicine

Houston, Texas, United States, 77030

Houston Methodist Cancer Center

Houston, Texas, United States, 77030

Harris Health System-Smith Clinic

Houston, Texas, United States, 77054

Texas Oncology - McAllen South Second

McAllen, Texas, United States, 78503

Texas Oncology Midland Allison Cancer Center

Midland, Texas, United States, 79701

Texas Oncology Plano

Plano, Texas, United States, 75075

Texas Oncology - The Woodlands

The Woodlands, Texas, United States, 77380

United States, Virginia

Wellmont Medical Associates-Oncology and Hematology

Bristol, Virginia, United States, 24201

Virginia Cancer Care Specialist

Leesburg, Virginia, United States, 20176

Centra Lynchburg Hematology Oncology

Lynchburg, Virginia, United States, 24501

Bon Secours Richmond Community Hospital Medical Oncology Associates at Memorial Regional Medical Center

Mechanicsville, Virginia, United States, 23116

Bon Secours St Francis Medical Center

Midlothian, Virginia, United States, 23114

Southwest Virginia Regional Cancer Center

Norton, Virginia, United States, 24273

Bon Secours Richmond Community Hospital Oncology Associates at St. Mary's Hospital

Richmond, Virginia, United States, 23226

United States, Washington

MRCC Auburn

Auburn, Washington, United States, 98001

MRCC Gig Harbor

Gig Harbor, Washington, United States, 98335

MRCC Puyallup

Puyallup, Washington, United States, 98372

MultiCare Health System

Tacoma, Washington, United States, 98405

MultiCare Institute for Research & Innovation

Tacoma, Washington, United States, 98405

United States, West Virginia

CAMC Health Education and Research Institute

Charleston, West Virginia, United States, 25304

West Virginia University

Morgantown, West Virginia, United States, 26506

United States, Wisconsin

Aurora Cancer Care-Southern Lakes

Burlington, Wisconsin, United States, 53105

Aurora Health Center Fond du Lac

Fond Du Lac, Wisconsin, United States, 54937

Aurora Cancer Care-Germantown Health Center

Germantown, Wisconsin, United States, 53022

Aurora Cancer Care-Grafton

Grafton, Wisconsin, United States, 53024

Aurora BayCare Medical Center

Green Bay, Wisconsin, United States, 54311

Aurora Cancer Care-Kenosha South

Kenosha, Wisconsin, United States, 53142

Aurora Cancer Care

Milwaukee, Wisconsin, United States, 53209

Aurora Cancer Care-Milwaukee South

Milwaukee, Wisconsin, United States, 53215

Aurora St. Lukes Medical Center-Pharmacy Only

Milwaukee, Wisconsin, United States, 53215

Aurora West Allis Medical Center

Milwaukee, Wisconsin, United States, 53227

Aurora Sinai Medical Center

Milwaukee, Wisconsin, United States, 53233

Vince Lombardi Cancer Clinic Oshkosh

Oshkosh, Wisconsin, United States, 54904

Aurora Cancer Care-Racine

Racine, Wisconsin, United States, 53406

Vince Lombardi Cancer Clinic Sheboygan

Sheboygan, Wisconsin, United States, 53081

Aurora Medical Center in Summit

Summit, Wisconsin, United States, 53066

Vince Lombardi Cancer Clinic-Two Rivers

Two Rivers, Wisconsin, United States, 54241

Aurora Cancer Care

Wauwatosa, Wisconsin, United States, 53226

Canada, Quebec

CIUSSS de l'Est-de-l'Ile-de-Montreal-Hopital-Maisonneuve-Rosemont

Montréal, Quebec, Canada, H1T2M4

Centre Hospitalier d'Universite de Montreal CHUM-Hotel Dieu

Montréal, Quebec, Canada, H2XOA9

SMBD-Jewish General Hospital (MPSG)

Montréal, Quebec, Canada, H3T 1E2

McGill University Health Centre-Cedars Cancer Centre

Montréal, Quebec, Canada, H4A3J1

CHU de Quebec-Hospital du Saint-Sacrement

Quebec City, Quebec, Canada, G1S4L8

Sponsors and Collaborators

NSABP Foundation Inc

Genentech, Inc.

Hoffmann-La Roche

Investigators

• Principal Investigator: Norman Wolmark, MD; NSBP Foundation, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Perez-Garcia J, Soberino J, Racca F, Gion M, Stradella A, Cortes J. Atezolizumab in the treatment of metastatic triple-negative breast cancer. Expert Opin Biol Ther. 2020 Sep;20(9):981-989. doi: 10.1080/14712598.2020.1769063. Epub 2020 May 25.

• Responsible Party: NSABP Foundation Inc
• ClinicalTrials.gov Identifier: NCT03281954
• Other Study ID Numbers: NSABP B-59/GBG 96-GeparDouze; 2017-002771-25 ( EudraCT Number ); MO39875 ( Other Identifier: Genentech, Inc. )
• First Posted: September 13, 2017
• Last Update Posted: March 7, 2023
• Last Verified: March 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by NSABP Foundation Inc:

anti-PD-L1 antibody; TNBC

Additional relevant MeSH terms:

Breast Neoplasms; Triple Negative Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Atezolizumab; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Antineoplastic Agents