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NCT03424005PHASE1, PHASE2Recruiting

A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer

Hoffmann-La Roche

Start Date

3/30/2018

Completion Date

9/30/2030

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, seven 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-naïve cohort). Cohort 3, 5, 6 and 7 will consist of participants with locally advanced or metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative disease with one or more PIK3CA mutations. Cohort 4 will consist of participants with locally advanced or metastatic HER2+ /HER2-low disease with one or more PIK3CA mutations 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). During Stage 2, 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, provided Stage 2 is open for enrollment and all eligibility criteria are met.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria 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 * Eastern cooperative oncology group (ECOG) performance status of 0 or 1 * Able to comply with the study protocol, in the investigator's judgment * Metastatic or inoperable locally advanced adenocarcinoma of the breast * 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 Exclusion Criteria Exclusion Criteria for Stage 1 * Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40 agonists or interleukin-2 (IL-2) or IL-2-like compounds * Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment * Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study * Eligibility only for the control arm Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort) * Adverse events from prior anti-cancer therapy that have not resolved to Grade \</= 1 or better with the exception of alopecia of any grade and Grade \</= 2 peripheral neuropathy * Treatment with investigational therapy within 28 days prior to initiation of study treatment * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) * Uncontrolled tumor-related pain * Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases * History of leptomeningeal disease * Active or history of autoimmune disease or immune deficiency * History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. * Active tuberculosis * Severe infection within 4 weeks prior to initiation of study treatment * Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment * Significant cardiovascular disease * Prior allogeneic stem cell or solid organ transplantation * History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death * Pregnancy or breastfeeding, or intention of becoming pregnant during the study

Interventions

DRUG

Capecitabine

DRUG

Atezolizumab

DRUG

Ipatasertib

DRUG

SGN-LIV1A

DRUG

Bevacizumab

DRUG

Chemotherapy (Gemcitabine + Carboplatin or Eribulin)

DRUG

Selicrelumab

DRUG

Tocilizumab

DRUG

Nab-Paclitaxel

DRUG

Sacituzumab Govitecan

DRUG

Abemaciclib

DRUG

Fulvestrant

DRUG

Ribociclib (Dose #1)

DRUG

Inavolisib (Dose #1)

DRUG

Trastuzumab Deruxtecan

DRUG

Ribociclib (Dose #2)

DRUG

Letrozole

DRUG

Inavolisib (Dose #2)

DRUG

Empagliflozin

DRUG

Palbociclib

DRUG

Metformin

DRUG

Atirmociclib

DRUG

Giredestrant

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Conditions

Metastatic Breast Cancer

Locations

City of Hope

Duarte, California 91010

United States

University of California San Diego Medical Center

La Jolla, California 92093

United States

Stanford Cancer Institute

Stanford, California 94305

United States

Rocky Mountain Cancer Center - Longmont

Longmont, Colorado 80501

United States

H. Lee Moffitt Cancer Center and Research Inst.

Tampa, Florida 33612

United States

Metro-Minnesota Community Oncology Research Consortium

Saint Paul, Minnesota 55101-2502

United States

Renown Regional Medical Center

Reno, Nevada 89502-1576

United States

Hackensack Univ Medical Center

Hackensack, New Jersey 07601

United States

Regional Cancer Care Associates, LLC

Howell Township, New Jersey 07731

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey 08901

United States

NYU Langone Medical Center

New York, New York 10016

United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania 19107

United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania 15213

United States

Tennessee Oncology - Chattanooga Oncology & Hematology Associates

Chattanooga, Tennessee 37404

United States

The West Clinic

Germantown, Tennessee 38138

United States

Tennessee Oncology PLLC

Nashville, Tennessee 37203

United States

Vanderbilt University Medical Center

Nashville, Tennessee 37212

United States

Texas Oncology-Plano East

Plano, Texas 75075-7787

United States

Peter MacCallum Cancer Centre-East Melbourne

Melbourne, Victoria 3000

Australia

Fiona Stanley Hospital - Medical Oncology

Murdoch, Western Australia 6150

Australia

Centre Léon Bérard

Lyon, 69008

France

Institut régional du Cancer Montpellier

Montpellier, 34298

France

Institut Universitaire du Cancer de Toulouse-Oncopole

Toulouse, 31059

France

Gustave Roussy

Villejuif, 94805

France

Universitätsklinikum Erlangen

Erlangen, 91054

Germany

Universitätsklinikum Essen

Essen, 45147

Germany

Rambam Medical Center

Haifa, 3109601

Israel

Shaare Zedek Medical Center

Jerusalem, 9103102

Israel

Hadassah University Medical Center

Jerusalem, 91120

Israel

Rabin MC

Petah Tikva, 55900

Israel

Sheba Medical Center

Ramat Gan, 5262100

Israel

Tel-Aviv Sourasky Medical Center

Tel Aviv, 6423906

Israel

Assuta Medical Centers

Tel Aviv, 69710

Israel

National Cancer Center Clinical Trials Center / Center for Breast Cancer

Goyang-si, 410-769

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

Severance Hospital

Seoul, 03722

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Hospital Universitario Virgen Macarena

Seville, Sevilla 41009

Spain

Hospital del Mar

Barcelona, 08003

Spain

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035

Spain

Hospital Universitario Ramon y Cajal

Madrid, 28034

Spain

Centro Integral Oncológico Clara Campal Ensayos Clínicos START

Madrid, 28050

Spain

National Cheng Kung University Hospital

Tainan, 704302

Taiwan

National Taiwan University Hospital

Taipei, 100

Taiwan

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN

United Kingdom

Barts Health NHS Trust - St Bartholomew's Hospital

London, EC1A 7BE

United Kingdom