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
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 tumour 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.
Trial Description
Primary Outcome:
- Pathologic complete response in the breast and lymph nodes (ypT0/Tis ypN0)
- Event-free survival (EFS)
Secondary Outcome:
- 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 (OS)
- Recurrence-free interval (RFI)
- Distant disease-free survival (DDFS)
- Brain metastases free survival
- Frequency of Adverse Events
- Frequency of immune Adverse Events of Special Interest
- Cardiac safety lead-in (Troponin-T)
- Cardiac safety lead-in (Troponin-T)
- Cardiac safety lead-in (Troponin-T)
- Cardiac safety lead-in (Left ventricular ejection fraction; LVEF)
- Cardiac safety lead-in (Left ventricular ejection fraction; LVEF)
- Cardiac safety lead-in (Left ventricular ejection fraction; LVEF)
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.
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 tumour (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 tumour 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 tumour 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 tumour containing the
maximum amount of tumour 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 for this study will be 1,520 randomized patients. It is expected that
approximately 760 patients will be randomized by sites in North America and
approximately 760 patients, by sites in Europe.
View this trial on ClinicalTrials.gov
