Ignite Creation Date:
2024-05-06 @ 10:33 AM
Last Modification Date:
2024-10-26 @ 12:31 PM
Study NCT ID:
NCT03281954
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-04-08
First Post:
2017-09-08
Brief Title:
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
Organization:
NSABP Foundation Inc
Study Overview
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
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
NSABP B-59GBG 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 atezolizumabplacebo in patients with high risk triple-negative breast cancer the potential incremental efficacy and safety of neoadjuvant administration of atezolizumabplacebo with a sequential regimen of weekly paclitaxel with every-3-week carboplatin followed immediately by neoadjuvant administration of atezolizumabplacebo with ACEC will be evaluated Patients will then undergo surgery Following recovery from surgery patients will initiate approximately 6 months of adjuvant therapy with atezolizumabplacebo 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 atezolizumabplacebo will be administered concurrently Adjuvant atezolizumabplacebo 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 atezolizumabplacebo 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 atezolizumabplacebo
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 ypT0Tis ypN0 and 2 to determine the value of atezolizumab in improving event-free survival EFS Secondary aims include pathologic complete response in the breast ypT0Tis 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 11-30 cm 30 cm 2 nodal status as determined by protocol-specified criteria negative positive 3 ACEC 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 patients tumor to be ER-negative PgR-negative and HER2-negative by current ASCOCAP 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 ERPgR 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 ACEC The safety lead-in will consist of assessment of ECG and serum troponin-T obtained just prior to administration of the first dose of ACEC following completion of the administration of the 1st and 3rd cycle of ACEC prior to initiation of the atezolizumabplacebo An additional assessment of LVEF with echocardiogram or MUGA scan will also be obtained prior to the 3rd dose of ACEC 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 ACEC undergo their scheduled post-surgery LVEF assessment When the last of the first 60 patients to initiate ACEC 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 atezolizumabplacebo 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 10 cm If gross residual disease is less than 10 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-59GBG 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 070 attributed to the addition of atezolizumab assuming a lost-to-follow-up rate of 000083 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 07 between the atezolizumab and the placebo arm at an overall 2-sided alpha level of 005
In this clinical trial of neoadjuvant and adjuvant administration of atezolizumabplacebo in patients with high risk triple-negative breast cancer the potential incremental efficacy and safety of neoadjuvant administration of atezolizumabplacebo with a sequential regimen of weekly paclitaxel with every-3-week carboplatin followed immediately by neoadjuvant administration of atezolizumabplacebo with ACEC will be evaluated Patients will then undergo surgery Following recovery from surgery patients will initiate approximately 6 months of adjuvant therapy with atezolizumabplacebo 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 atezolizumabplacebo will be administered concurrently Adjuvant atezolizumabplacebo 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 atezolizumabplacebo 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 atezolizumabplacebo
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 ypT0Tis ypN0 and 2 to determine the value of atezolizumab in improving event-free survival EFS Secondary aims include pathologic complete response in the breast ypT0Tis 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 11-30 cm 30 cm 2 nodal status as determined by protocol-specified criteria negative positive 3 ACEC 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 patients tumor to be ER-negative PgR-negative and HER2-negative by current ASCOCAP 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 ERPgR 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 ACEC The safety lead-in will consist of assessment of ECG and serum troponin-T obtained just prior to administration of the first dose of ACEC following completion of the administration of the 1st and 3rd cycle of ACEC prior to initiation of the atezolizumabplacebo An additional assessment of LVEF with echocardiogram or MUGA scan will also be obtained prior to the 3rd dose of ACEC 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 ACEC undergo their scheduled post-surgery LVEF assessment When the last of the first 60 patients to initiate ACEC 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 atezolizumabplacebo 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 10 cm If gross residual disease is less than 10 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-59GBG 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 070 attributed to the addition of atezolizumab assuming a lost-to-follow-up rate of 000083 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 07 between the atezolizumab and the placebo arm at an overall 2-sided alpha level of 005
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| MO39875 | OTHER | Genentech Inc | None |
| 2017-002771-25 | EUDRACT_NUMBER | None | None |