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

• Sponsor: NSABP Foundation Inc (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03281954
• Collaborator: Genentech, Inc. (Industry), Hoffmann-La Roche (Industry)
• Enrollment: 1,550
• Locations: 217
• Arms: 2
• Anticipated Duration (Months): 78.4
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.1

Study Details

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
• 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: Dec 19, 2017
• Anticipated Primary Completion Date: Dec 31, 2023
• Anticipated Study Completion Date: Jun 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) [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) [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) [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) [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) [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 [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 [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) [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) [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) [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) [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) [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) [Four to 6 weeks after surgery]

    LVEF levels measured after surgery

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama	United States	36604
2	Katmai Oncology Group	Anchorage	Alaska	United States	99508
3	St. Bernard's Medical Center	Jonesboro	Arkansas	United States	72401
4	St. Bernard's Medical Center	Paragould	Arkansas	United States	72450
5	Kaiser Permanente-Anaheim	Anaheim	California	United States	92806
6	Kaiser Permanente-Baldwin Park	Baldwin Park	California	United States	91706
7	Kaiser Permanente-Bellflower	Bellflower	California	United States	90706
8	Arrowhead Regional Medical Center	Colton	California	United States	92324
9	City of Hope	Duarte	California	United States	91010
10	Kaiser Permanente-Fontana	Fontana	California	United States	92335
11	Kaiser Permanente-Harbor City	Harbor City	California	United States	90710
12	Kaiser Permanente-Irvine	Irvine	California	United States	92618
13	Cancer and Blood Specialty Clinic	Los Alamitos	California	United States	90720
14	Kaiser Permanente-Sunset	Los Angeles	California	United States	90027
15	Kaiser Permanente-West Los Angeles	Los Angeles	California	United States	90034
16	Kaiser Permanente-Panorama City	Panorama City	California	United States	91402
17	Kaiser Permanente-Riverside	Riverside	California	United States	92505
18	Kaiser Permanente Medical Group	San Diego	California	United States	92108
19	Kaiser Permanente-Zion	San Diego	California	United States	92120
20	Kaiser Permanente - Otay	San Diego	California	United States	92153
21	Kaiser Permanente- San Marcos	San Marcos	California	United States	92078
22	City of Hope - South Pasadena	South Pasadena	California	United States	91030
23	Torrance Memorial Physician Network	Torrance	California	United States	90505
24	City of Hope - Upland	Upland	California	United States	91786
25	PIH Health	Whittier	California	United States	90602
26	Kaiser Permanente-Woodland Hills	Woodland Hills	California	United States	91367
27	Mount Sinai Comprehensive Cancer Center Aventura	Aventura	Florida	United States	33180
28	Memorial Healthcare System Office of Human Research	Hollywood	Florida	United States	33021
29	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida	United States	33140
30	UF Health Cancer Center at Orlando Health	Orlando	Florida	United States	32806
31	Gwinnett Hospital System Center for Cancer Care	Duluth	Georgia	United States	30096
32	Gwinnett Hospital System Center for Cancer Care	Lawrenceville	Georgia	United States	30046
33	Gwinnett Hospital System Center for Cancer Care	Snellville	Georgia	United States	30078
34	Illinois Cancer Care-Bloomington	Bloomington	Illinois	United States	61704
35	Affiliated Oncologists	Chicago Ridge	Illinois	United States	60415
36	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois	United States	60612
37	Rush University Medical Center	Chicago	Illinois	United States	60612
38	Cancer Care Specialists of Central Illinois	Decatur	Illinois	United States	62526
39	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
40	Crossroads Cancer Center	Effingham	Illinois	United States	62401
41	Emhurst Memorial Nancy W. Knowles Cancer Center	Elmhurst	Illinois	United States	60126
42	Illinois Cancer Care-Galesburg	Galesburg	Illinois	United States	61401
43	Edward Cancer Center	Naperville	Illinois	United States	60540
44	Illinois Cancer Care-Ottawa	Ottawa	Illinois	United States	61350
45	Illinois Cancer Care PC	Peoria	Illinois	United States	61615
46	Illinois Cancer Care-Peru	Peru	Illinois	United States	61354
47	Edward Cancer Center Plainfield	Plainfield	Illinois	United States	60585
48	Cancer Care Specialists of Central Illinois-Swansea	Swansea	Illinois	United States	62226
49	Fort Wayne Medical Oncology and Hematology Inc (W. Jefferson Blvd)	Fort Wayne	Indiana	United States	46804
50	Fort Wayne Medical Oncology and Hematology Inc (Parkview Plaza)	Fort Wayne	Indiana	United States	46845
51	Mercy Medical Center Hall-Perrine Cancer Center	Cedar Rapids	Iowa	United States	52403
52	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
53	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
54	Susan B. Allen Memorial Hosptial	El Dorado	Kansas	United States	67042
55	Cancer Center at Mercy - W. Laurel	Independence	Kansas	United States	67301
56	Kingman Community Hospital	Kingman	Kansas	United States	67068
57	Southwest Medical Center	Liberal	Kansas	United States	67901
58	McPherson Center for Health	McPherson	Kansas	United States	67460
59	Newton Medical Center	Newton	Kansas	United States	67114
60	Labette Health	Parsons	Kansas	United States	67357
61	Pratt Regional Medical Center	Pratt	Kansas	United States	67124
62	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
63	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
64	Cancer Center of Kansas	Wichita	Kansas	United States	67214
65	Winfield Healthcare Center	Winfield	Kansas	United States	67156
66	Norton Cancer Institute-Downtown	Louisville	Kentucky	United States	40202
67	Norton Cancer Institute-Norton Healthcare Pavilion	Louisville	Kentucky	United States	40202
68	University of Louisville-James Graham Brown Cancer Center	Louisville	Kentucky	United States	40202
69	Baptist Health Louisville; Consultants in Blood Disorders and Cancer	Louisville	Kentucky	United States	40207
70	Norton Cancer Institute-St Matthews	Louisville	Kentucky	United States	40207
71	Norton Cancer Institute-Brownsboro	Louisville	Kentucky	United States	40241
72	Ochsner Medical Center-Kenner	Kenner	Louisiana	United States	70065
73	West Jefferson Medical Center Cancer Center	Marrero	Louisiana	United States	70072
74	University Medical Center New Orleans	New Orleans	Louisiana	United States	70112
75	Ochsner Medical Center	New Orleans	Louisiana	United States	70121
76	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
77	Medstar Union Memorial Hospital	Baltimore	Maryland	United States	21218
78	Harry and Jeanette Weinberg Cancer Center at Franklin Square	Baltimore	Maryland	United States	21237
79	Maryland Oncology Hematology	Bethesda	Maryland	United States	20817
80	Maryland Oncology - Hematology Brandywine	Brandywine	Maryland	United States	20613
81	Maryland Oncology - Hematology PA	Columbia	Maryland	United States	21044
82	Maryland Oncology - Hematology Frederick	Frederick	Maryland	United States	21702
83	Meritus Center for Clinical Research	Hagerstown	Maryland	United States	21742
84	Maryland Oncology - Hematology PA	Lanham	Maryland	United States	20706
85	Maryland Oncology Hematology	Rockville	Maryland	United States	20850
86	Capital Hematology Oncology Associates	Silver Spring	Maryland	United States	20904
87	Holy Cross Hospital	Silver Spring	Maryland	United States	20910
88	University of Maryland, St. Joseph Medical Center	Towson	Maryland	United States	21204
89	Maryland Oncology Hematology	Wheaton	Maryland	United States	20902
90	Berkshire Hematology Oncology Services at Berkshire Medical Center Cancer and Infusion Center	Pittsfield	Massachusetts	United States	01201
91	Henry Ford Cancer Institute Brownstown	Brownstown	Michigan	United States	48183
92	Henry Ford Cancer Institute Macomb Hospital	Clinton Township	Michigan	United States	48038
93	Henry Ford Medical Center Fairlane	Dearborn	Michigan	United States	48126
94	Henry Ford Hospital	Detroit	Michigan	United States	48202
95	Michigan State University	East Lansing	Michigan	United States	48823
96	Henry Ford Allegiance Health	Jackson	Michigan	United States	49201
97	Michigan State University-Breslin Cancer Center	Lansing	Michigan	United States	48910
98	Henry Ford Medical Center Columbus	Novi	Michigan	United States	48377
99	Henry Ford Hospital W Bloomfield	West Bloomfield	Michigan	United States	48322
100	Henry Ford Cancer Institute Wyandotte Hospital	Wyandotte	Michigan	United States	48192
101	University of Missouri-Ellis Fischel Cancer Center	Columbia	Missouri	United States	65212
102	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
103	MD Anderson Cancer Center at Cooper	Voorhees	New Jersey	United States	08043
104	New York Oncology Hematology PC	Albany	New York	United States	12206
105	Broome Oncolgy	Binghamton	New York	United States	13905
106	Broome Oncology	Johnson City	New York	United States	13790
107	Health Quest Medical Practice	Poughkeepsie	New York	United States	12601
108	Vassar Brothers Medical Center	Poughkeepsie	New York	United States	12601
109	RHOA of Cary	Cary	North Carolina	United States	27518
110	Waverly Hematology Oncology	Cary	North Carolina	United States	27518
111	Carolinas Medical Center-Levine Cancer Insitute	Charlotte	North Carolina	United States	28204
112	Levine Cancer Center Institute Pineville	Charlotte	North Carolina	United States	28210
113	RHOA of Garner	Garner	North Carolina	United States	27529
114	UNC Regional Physicians Hematology and Oncolgoy	High Point	North Carolina	United States	27262
115	FirstHealth of the Carolinas FirstHealth Outpatient Cancer Center	Pinehurst	North Carolina	United States	28374
116	Rex Cancer Center	Raleigh	North Carolina	United States	27607
117	RHOA of Blue Ridge	Raleigh	North Carolina	United States	27607
118	RCC of Wakefield	Raleigh	North Carolina	United States	27614
119	Nash UNC Health Care - Danny Talbott Cancer Center	Rocky Mount	North Carolina	United States	28704
120	Sanford Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
121	Aultman Alliance Cancer Center	Alliance	Ohio	United States	44601
122	Aultman Hospital	Canton	Ohio	United States	44710
123	Aultman Medical Group Hematology and Oncology	Canton	Ohio	United States	44710
124	The Ohio State University Wexner Medical Center-Investigational Drug Service Oncology	Columbus	Ohio	United States	43210
125	The Stephanie Speilman Comprehensive Breast Center	Columbus	Ohio	United States	43212
126	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon	United States	97401
127	Kaiser Permanente Northwest-Oncology/Hematology	Portland	Oregon	United States	97227
128	Northwest Cancer Specialists	Tigard	Oregon	United States	97223
129	UPMC Hillman Cancer Center-Beaver	Beaver	Pennsylvania	United States	15009
130	UPMC Hillman Cancer Center - Passavant North	Cranberry Township	Pennsylvania	United States	16066
131	Ephrata Cancer Center	Ephrata	Pennsylvania	United States	17522
132	Allegheny Cancer Institute St. Vincent	Erie	Pennsylvania	United States	16505
133	St. Vincent Hospital	Erie	Pennsylvania	United States	16544
134	UPMC Cancer Center Horizon	Farrell	Pennsylvania	United States	16121
135	Wellspan Medical Oncology	Gettysburg	Pennsylvania	United States	17325
136	UPMC Hillman Cancer Center- Mountain View	Greensburg	Pennsylvania	United States	15601
137	UPMC Cancer Center Greenville	Greenville	Pennsylvania	United States	16125
138	AHN Cancer Institute at Jefferson	Jefferson Hills	Pennsylvania	United States	15025
139	Seechler Family Cancer Center	Lebanon	Pennsylvania	United States	17042
140	Forbes Regional Hospital	Monroeville	Pennsylvania	United States	15146
141	UPMC Hillman Cancer Center UPMC East-Monroeville	Monroeville	Pennsylvania	United States	15146
142	UPMC Hillman Cancer Center Norwin	N. Huntingdon	Pennsylvania	United States	15642
143	UPMC Hillman Cancer Center New Castle	New Castle	Pennsylvania	United States	16105
144	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
145	WPAON at AGH	Pittsburgh	Pennsylvania	United States	15212
146	WPAON at WPH	Pittsburgh	Pennsylvania	United States	15212
147	Magee-Women's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
148	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224
149	UPCI Investigational Drug Services	Pittsburgh	Pennsylvania	United States	15232
150	UPMC Hillman Cancer Center @ Passavant - HOA	Pittsburgh	Pennsylvania	United States	15237
151	UPMC Hillman Cancer Center @ Passavant - OHA	Pittsburgh	Pennsylvania	United States	15237
152	UPMC Hillman Cancer Center-Upper Saint Clair	Pittsburgh	Pennsylvania	United States	15243
153	UPMC Cancer Center Northwest	Seneca	Pennsylvania	United States	16346
154	UPMC Hillman Cancer Center - Uniontown	Uniontown	Pennsylvania	United States	15401
155	UPMC Hillman Cancer Center-Washington	Washington	Pennsylvania	United States	15301
156	Wexford Health & Wellness Pavilion	Wexford	Pennsylvania	United States	15090
157	Cancer Care Associates of York	York	Pennsylvania	United States	17403
158	Wellspan Health-York Cancer Center Oncology Research	York	Pennsylvania	United States	17403
159	Women's and Infants Hospital	Providence	Rhode Island	United States	02905
160	Gibbs Cancer Center and Research Institute - Pelham	Greer	South Carolina	United States	29651
161	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
162	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
163	Avera Cancer Institute-Sioux Falls	Sioux Falls	South Dakota	United States	57105
164	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
165	Wellmont Cancer Institute	Johnson City	Tennessee	United States	37601
166	Wellmont Cancer Institute	Kingsport	Tennessee	United States	37660
167	Dell Seton Medical Center at the University of Texas-Seton Infusion Center	Austin	Texas	United States	72701
168	Texas Oncology Bedford	Bedford	Texas	United States	76022
169	Texas Oncology Carrollton	Carrollton	Texas	United States	75010
170	Texas Oncology - Methodist Dallas Cancer Center	Dallas	Texas	United States	75203
171	Texas Oncology - Medical City Dallas	Dallas	Texas	United States	75230
172	Texas Oncology Dallas Presbyterian Hospital	Dallas	Texas	United States	75231
173	Texas Oncology Denton	Denton	Texas	United States	76201
174	Texas Oncology Flower Mound	Flower Mound	Texas	United States	75028
175	Baylor College of Medicine	Houston	Texas	United States	77030
176	Houston Methodist Cancer Center	Houston	Texas	United States	77030
177	Harris Health System-Smith Clinic	Houston	Texas	United States	77054
178	Texas Oncology - McAllen South Second	McAllen	Texas	United States	78503
179	Texas Oncology Midland Allison Cancer Center	Midland	Texas	United States	79701
180	Texas Oncology Plano	Plano	Texas	United States	75075
181	Texas Oncology - The Woodlands	The Woodlands	Texas	United States	77380
182	Wellmont Medical Associates-Oncology and Hematology	Bristol	Virginia	United States	24201
183	Virginia Cancer Care Specialist	Leesburg	Virginia	United States	20176
184	Centra Lynchburg Hematology Oncology	Lynchburg	Virginia	United States	24501
185	Bon Secours Richmond Community Hospital Medical Oncology Associates at Memorial Regional Medical Center	Mechanicsville	Virginia	United States	23116
186	Bon Secours St Francis Medical Center	Midlothian	Virginia	United States	23114
187	Southwest Virginia Regional Cancer Center	Norton	Virginia	United States	24273
188	Bon Secours Richmond Community Hospital Oncology Associates at St. Mary's Hospital	Richmond	Virginia	United States	23226
189	MRCC Auburn	Auburn	Washington	United States	98001
190	MRCC Gig Harbor	Gig Harbor	Washington	United States	98335
191	MRCC Puyallup	Puyallup	Washington	United States	98372
192	MultiCare Health System	Tacoma	Washington	United States	98405
193	MultiCare Institute for Research & Innovation	Tacoma	Washington	United States	98405
194	CAMC Health Education and Research Institute	Charleston	West Virginia	United States	25304
195	West Virginia University	Morgantown	West Virginia	United States	26506
196	Aurora Cancer Care-Southern Lakes	Burlington	Wisconsin	United States	53105
197	Aurora Health Center Fond du Lac	Fond Du Lac	Wisconsin	United States	54937
198	Aurora Cancer Care-Germantown Health Center	Germantown	Wisconsin	United States	53022
199	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
200	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
201	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
202	Aurora Cancer Care	Milwaukee	Wisconsin	United States	53209
203	Aurora Cancer Care-Milwaukee South	Milwaukee	Wisconsin	United States	53215
204	Aurora St. Lukes Medical Center-Pharmacy Only	Milwaukee	Wisconsin	United States	53215
205	Aurora West Allis Medical Center	Milwaukee	Wisconsin	United States	53227
206	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
207	Vince Lombardi Cancer Clinic Oshkosh	Oshkosh	Wisconsin	United States	54904
208	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
209	Vince Lombardi Cancer Clinic Sheboygan	Sheboygan	Wisconsin	United States	53081
210	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
211	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
212	Aurora Cancer Care	Wauwatosa	Wisconsin	United States	53226
213	CIUSSS de l'Est-de-l'Ile-de-Montreal-Hopital-Maisonneuve-Rosemont	Montréal	Quebec	Canada	H1T2M4
214	Centre Hospitalier d'Universite de Montreal CHUM-Hotel Dieu	Montréal	Quebec	Canada	H2XOA9
215	SMBD-Jewish General Hospital (MPSG)	Montréal	Quebec	Canada	H3T 1E2
216	McGill University Health Centre-Cedars Cancer Centre	Montréal	Quebec	Canada	H4A3J1
217	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.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NSABP Foundation Inc
• ClinicalTrials.gov Identifier: NCT03281954
• Other Study ID Numbers: NSABP B-59/GBG 96-GeparDouze; 2017-002771-25; MO39875
• First Posted: Sep 13, 2017
• Last Update Posted: Aug 1, 2022
• Last Verified: Jul 1, 2022

• 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; Atezolizumab

Study Results

No Results Posted as of Aug 1, 2022