A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
Phase 1
Recruiting
- Conditions
- Metastatic Breast Cancer
- Interventions
- Drug: Chemotherapy (Gemcitabine + Carboplatin or Eribulin)
- Registration Number
- NCT03424005
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is an umbrella study evaluating the efficacy and safety of multiple treatment combinations in participants with metastatic or inoperable locally advanced breast cancer.
The study will be performed in two stages. During Stage 1, four cohorts will be enrolled in parallel in this study:
Cohort 1 will consist of Programmed death-ligand 1 (PD-L1)-positive participants who have received no prior systemic therapy for metastatic or inoperable locally advanced triple-negative breast cancer (TNBC) (first-line \[1L\] PD-L1+ cohort).
Cohort 2 will consist of participants who had disease progression during or following 1L treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not received cancer immunotherapy (CIT) (second-line \[2L\] CIT-naive cohort).
Cohort 3 will consist of participants with locally-advanced or metastatic HR+, HER2-negative disease with PIK3CA mutation who may or may not have had disease progression during or following previous lines of treatment for metastatic disease (HR+cohort).
Cohort 4 will consist of participants with locally-advanced or metastatic HER2+ /HER2-low disease with PIK3CA mutation who had disease progression on standard-of-care therapies (HER2+ /HER2-low cohort).
In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). In addition, participants in the 2L CIT-naïve cohort who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment combination (Stage 2), provided Stage 2 is open for enrollment.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 580
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab + Nab-Paclitaxel + Tocilizumab Nab-Paclitaxel 1L PD-L1-positive participants will receive combination treatment with atezolizumab plus nab-paclitaxel and tocilizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed. Capecitabine Capecitabine 2L CIT-naive participants will receive capecitabine until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1). Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed. Atezolizumab + Ipatasertib Ipatasertib 2L CIT-naive participants will receive doublet combination treatment with atezolizumab + ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed. Atezolizumab + Nab-Paclitaxel Nab-Paclitaxel 1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab + nab-paclitaxel until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed. Atezolizumab + Nab-Paclitaxel Atezolizumab 1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab + nab-paclitaxel until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed. Atezolizumab + Nab-Paclitaxel + Tocilizumab Atezolizumab 1L PD-L1-positive participants will receive combination treatment with atezolizumab plus nab-paclitaxel and tocilizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed. Atezolizumab + Sacituzumab Govitecan Sacituzumab Govitecan 1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus sacituzumab govitecan until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed. Inavolisib + Abemaciclib + Fulvestrant Fulvestrant Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus abemaciclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Atezolizumab + Sacituzumab Govitecan Atezolizumab 1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus sacituzumab govitecan until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed. Inavolisib + Ribociclib (dose #2) + Fulvestrant Ribociclib (dose #2) Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Inavolisib (dose #1) + Trastuzumab Deruxtecan Inavolisib (dose #1) HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. Inavolisib + Ribociclib (dose #1) + Fulvestrant Ribociclib (dose #1) Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Atezolizumab + Selicrelumab + Bevacizumab Atezolizumab 2L-CIT-naive participants will receive doublet combination treatment with atezolizumab plus selicrelumab and bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed. Inavolisib + Ribociclib (dose #2) + Letrozole Ribociclib (dose #2) Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Inavolisib (dose #2) + Trastuzumab Deruxtecan Inavolisib (dose #2) HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. Atezolizumab + SGN-LIV1A SGN-LIV1A 2L CIT-naive participants will receive doublet combination treatment with atezolizumab plus SGNLIV1A until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed. Inavolisib + Ribociclib (dose #1) + Letrozole Ribociclib (dose #1) Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin) Chemotherapy (Gemcitabine + Carboplatin or Eribulin) 2L CIT-naive participants enrolled in the active comparator arm who experience disease progression per RECIST v1.1 and 2L CIT-naive participants enrolled in an experimental arm who experience loss of clinical benefit as determined by the investigator may receive doublet combination treatment with atezolizumab plus chemotherapy (gemcitabine + carboplatin or eribulin) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed. Inavolisib + Ribociclib (dose #2) + Letrozole Inavolisib Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Atezolizumab + Nab-Paclitaxel + Tocilizumab Tocilizumab 1L PD-L1-positive participants will receive combination treatment with atezolizumab plus nab-paclitaxel and tocilizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed. Atezolizumab + Ipatasertib Atezolizumab 2L CIT-naive participants will receive doublet combination treatment with atezolizumab + ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed. Atezolizumab + SGN-LIV1A Atezolizumab 2L CIT-naive participants will receive doublet combination treatment with atezolizumab plus SGNLIV1A until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed. Atezolizumab + Selicrelumab + Bevacizumab Bevacizumab 2L-CIT-naive participants will receive doublet combination treatment with atezolizumab plus selicrelumab and bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed. Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin) Atezolizumab 2L CIT-naive participants enrolled in the active comparator arm who experience disease progression per RECIST v1.1 and 2L CIT-naive participants enrolled in an experimental arm who experience loss of clinical benefit as determined by the investigator may receive doublet combination treatment with atezolizumab plus chemotherapy (gemcitabine + carboplatin or eribulin) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed. Inavolisib + Abemaciclib + Fulvestrant Abemaciclib Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus abemaciclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Inavolisib + Abemaciclib + Fulvestrant Inavolisib Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus abemaciclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Inavolisib (dose #1) + Trastuzumab Deruxtecan Trastuzumab Deruxtecan HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. Inavolisib + Ribociclib (dose #2) + Fulvestrant Fulvestrant Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Inavolisib + Ribociclib (dose #1) + Letrozole Letrozole Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Inavolisib + Ribociclib (dose #1) + Letrozole Inavolisib Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Inavolisib + Ribociclib (dose #1) + Fulvestrant Inavolisib Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Inavolisib + Ribociclib (dose #2) + Letrozole Letrozole Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Inavolisib + Abemaciclib + Letrozole Inavolisib Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus abemaciclib plus letrozole until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Inavolisib + Abemaciclib + Letrozole Letrozole Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus abemaciclib plus letrozole until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Atezolizumab + Selicrelumab + Bevacizumab Selicrelumab 2L-CIT-naive participants will receive doublet combination treatment with atezolizumab plus selicrelumab and bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed. Inavolisib + Ribociclib (dose #2) + Fulvestrant Inavolisib Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Baseline until disease progression or loss of clinical benefit (up to approximately 10 years)
- Secondary Outcome Measures
Name Time Method Overall Survival (at specific time-points) 12 and 18 months Percentage of Participants with Adverse Events Baseline to end of study (up to approximately 10 years) Progression Free Survival (PFS) Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (up to approximately 10 years) as determined by the investigator according to RECIST v1.1 Disease Control Rate (DCR) Baseline through end of study (up to approximately 10 years) Duration of Response (DOR) Randomization until first occurrence of a documented objective response to the first recorded occurrence of disease progression or death from any cause (whichever occurs first), through end of study (up to approximately 10 years) Overall Survival (OS) Randomization to death from any cause, through the end of study (up to approximately 10 years)
Trial Locations
- Locations (42)
National Cheng Kung University Hospital
🇨🇳Tainan City, Taiwan
City of Hope
🇺🇸Duarte, California, United States
University of California San Diego Medical Center
🇺🇸La Jolla, California, United States
Stanford Cancer Institute
🇺🇸Stanford, California, United States
Rocky Mountain Cancer Center - Longmont
🇺🇸Longmont, Colorado, United States
H. Lee Moffitt Cancer Center and Research Inst.
🇺🇸Tampa, Florida, United States
Hackensack Univ Medical Center
🇺🇸Hackensack, New Jersey, United States
Regional Cancer Care Associates, LLC
🇺🇸Howell, New Jersey, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
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