A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Treatment Combinations In Patients With Metastatic Breast Cancer (Morpheus-panBC)

Who is this study for? Adult patients with metastatic or inoperable locally advanced triple negative breast cancer
Status: Recruiting
Location: See all (42) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

⁃ Patients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and to qualify for Stage 2 (2L CIT-naïve cohort):

• Age \>/= 18 years at the time of signing Informed Consent Form

• ECOG Performance Status of 0 or 1

• Able to comply with the study protocol, in the investigator's judgment

• Metastatic or inoperable locally advanced breast cancer

• Measurable disease (at least one target lesion) according to RECIST v1.1

• Life expectancy \>/= 3 months, as determined by the investigator

• Tumor accessible for biopsy, unless archival tissue is available

• Availability of a representative tumor specimen that is suitable for biomarker analysis via central testing

• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment

• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs, as outlined for each specific treatment arm

• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm

Locations
United States
California
City of Hope
COMPLETED
Duarte
University of California San Diego Medical Center
COMPLETED
La Jolla
Stanford Cancer Institute
WITHDRAWN
Stanford
Colorado
Rocky Mountain Cancer Center - Longmont
COMPLETED
Longmont
Florida
H. Lee Moffitt Cancer Center and Research Inst.
COMPLETED
Tampa
New Jersey
Hackensack Univ Medical Center
WITHDRAWN
Hackensack
Regional Cancer Care Associates, LLC
WITHDRAWN
Howell Township
Rutgers Cancer Institute of New Jersey
WITHDRAWN
New Brunswick
New York
NYU Langone Medical Center
WITHDRAWN
New York
Pennsylvania
Thomas Jefferson University Hospital
WITHDRAWN
Philadelphia
University of Pittsburgh Medical Center
WITHDRAWN
Pittsburgh
Tennessee
The West Clinic
RECRUITING
Germantown
Vanderbilt University Medical Center
RECRUITING
Nashville
Texas
Texas Oncology-Plano East
WITHDRAWN
Plano
Other Locations
Australia
Peter MacCallum Cancer Centre-East Melbourne
RECRUITING
Melbourne
Fiona Stanley Hospital - Medical Oncology
RECRUITING
Murdoch
France
Centre Léon Bérard
ACTIVE_NOT_RECRUITING
Lyon
Institut régional du Cancer Montpellier
WITHDRAWN
Montpellier
Institut Universitaire du Cancer de Toulouse-Oncopole
RECRUITING
Toulouse
Gustave Roussy
RECRUITING
Villejuif
Germany
Universitätsklinikum Erlangen
RECRUITING
Erlangen
Universitätsklinikum Essen
RECRUITING
Essen
Israel
Rambam Medical Center
RECRUITING
Haifa
Hadassah University Medical Center
RECRUITING
Jerusalem
Shaare Zedek Medical Center
RECRUITING
Jerusalem
Rabin MC
RECRUITING
Petah Tikva
Sheba Medical Center
RECRUITING
Ramat Gan
Assuta Medical Centers
RECRUITING
Tel Aviv
Tel-Aviv Sourasky Medical Center
RECRUITING
Tel Aviv
Republic of Korea
National Cancer Center Clinical Trials Center / Center for Breast Cancer
RECRUITING
Goyang-si
Samsung Medical Center
RECRUITING
Seoul
Seoul National University Hospital
RECRUITING
Seoul
Severance Hospital
RECRUITING
Seoul
University of Ulsan College of Medicine - Asan Medical Center
RECRUITING
Seoul
Spain
Hospital del Mar
RECRUITING
Barcelona
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
RECRUITING
Barcelona
Centro Integral Oncológico Clara Campal Ensayos Clínicos START
RECRUITING
Madrid
Hospital Universitario Ramon y Cajal
RECRUITING
Madrid
Hospital Universitario Virgen Macarena
RECRUITING
Seville
Taiwan
National Cheng Kung University Hospital
RECRUITING
Tainan City
United Kingdom
Beatson West of Scotland Cancer Centre
COMPLETED
Glasgow
Barts Health NHS Trust - St Bartholomew's Hospital
ACTIVE_NOT_RECRUITING
London
Contact Information
Primary
Reference Study ID Number: CO40115 https://forpatients.roche.com/
global-roche-genentech-trials@gene.com
888-662-6728 (U.S. and Canada)
Time Frame
Start Date: 2018-03-30
Estimated Completion Date: 2028-05-03
Participants
Target number of participants: 580
Treatments
Active_comparator: Atezolizumab + 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.
Experimental: Atezolizumab + Nab-Paclitaxel + 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.
Experimental: Atezolizumab + 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.
Active_comparator: 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.
Experimental: Atezolizumab + 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.
Experimental: Atezolizumab + 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.
Experimental: Atezolizumab + Selicrelumab + 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.
Experimental: Atezolizumab + Chemo (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.
Experimental: Inavolisib + Abemaciclib + 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).
Experimental: Inavolisib + Ribociclib (dose #2) + 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).
Experimental: Inavolisib (dose #1) + 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.
Experimental: Inavolisib + Ribociclib (dose #1) + 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).
Experimental: Inavolisib + Ribociclib (dose #1) + 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).
Experimental: Inavolisib + Ribociclib (dose #2) + 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).
Experimental: Inavolisib + Abemaciclib + 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).
Experimental: Inavolisib (dose #2) + 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.
Related Therapeutic Areas
Sponsors
Collaborators: Gilead Sciences
Leads: Hoffmann-La Roche

This content was sourced from clinicaltrials.gov

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