RecruitingPhase 1Phase 2NCT04802759

A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Breast Cancer (MORPHEUS-BREAST CANCER)


Sponsor

Hoffmann-La Roche

Enrollment

316 participants

Start Date

Jun 22, 2021

Study Type

INTERVENTIONAL

Conditions

Summary

This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with breast cancer. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the patient population. Cohort 1 will focus on participants with inoperable, locally advanced or metastatic, estrogen receptor-positive (ER+), HER2-negative breast cancer who had disease progression during or following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i; e.g., palbociclib, ribociclib, abemaciclib) in the first- or second-line setting. Cohort 2 will focus on inoperable, locally advanced or metastatic, ER+, HER2-positive breast cancer with previous progression to standard-of-care anti-HER2 therapies, of which one was a trastuzumab-and-taxane-based systemic therapy (including in the early setting if recurrence occurred within 6 months of finishing adjuvant therapy) and one was a HER2-targeting antibody-drug conjugate (ADC; e.g., ado-trastuzumab emtansine or trastuzumab-deruxtecan) or a HER2-targeting tyrosine kinase inhibitor (TKI; e.g., tucatinib, lapatinib, pyrotinib, or neratinib). Cohort 3 will focus on inoperable, locally advanced or metastatic, ER+, HER2-negative, PIK3CA-mutated breast cancer with resistance to adjuvant endocrine therapy.


Eligibility

Sex: FEMALEMin Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study is testing multiple different drug combinations in women with advanced breast cancer to find more effective treatments. It includes several groups based on tumor type — hormone receptor-positive, HER2-positive, and triple-negative breast cancer — each testing different targeted therapies or immunotherapies. **You may be eligible if...** - You are in good general health (ECOG 0-1) - You have advanced or metastatic breast cancer - Your specific tumor type (hormone receptor status, HER2 status) matches one of the study groups - Your cancer has not responded to or has progressed on standard treatments **You may NOT be eligible if...** - You have serious organ problems (heart, liver, kidney) - You have certain prior treatments that conflict with study drugs - Your cancer type does not match any of the study cohorts Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGGiredestrant

30 milligrams (mg) orally once a day (during each 28-day cycle or 21-day cycle, depending on the regimen) until unacceptable toxicity or disease progression

DRUGAbemaciclib

150 mg orally twice a day (during each 28-day cycle or 21-day cycle, depending on the regimen) until unacceptable toxicity or disease progression

DRUGIpatasertib

400 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression

DRUGInavolisib

9 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression

DRUGRibociclib

600 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression

DRUGEverolimus

10 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression

DRUGSamuraciclib

360 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression

DRUGPH FDC SC

On Day 1 of Cycle 1 (1 cycle is 21 days), pertuzumab and trastuzumab fixed-dose combination for subcutaneous use (PH FDC SC) will be administered SC as a fixed dose formulation of 1200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase. On Day 1 of Cycles 2 and beyond, PH FDC SC will be administered SC once every 21 days as a fixed dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase.

DRUGPalbociclib

125 mg orally once a day on Days 1-21 during each 28-day cycle until unacceptable toxicity or disease progression

DRUGAtezolizumab

840 mg by intravenous (IV) infusion on Days 1 and 15 each 28-day cycle.


Locations(31)

City of Hope

Duarte, California, United States

University of California, San Francisco (UCSF)

San Francisco, California, United States

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Santa Monica, California, United States

Stanford Cancer Institute (SCI)

Stanford, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Regional Cancer Care Associates LLC (RCCA) - Freehold Location

Freehold, New Jersey, United States

Regional Cancer Care Associates LLC ? Howell Division

Howell Township, New Jersey, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

West Cancer Center

Germantown, Tennessee, United States

Flinders Medical Centre

Bedford Park, South Australia, Australia

Peninsula Health-Frankston Hospital

Frankston, Victoria, Australia

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Linear Clinical Research Limited

Nedlands, Western Australia, Australia

Shaare Zedek Medical Center

Jerusalem, Jerusalem, Israel

Rambam Medical Center

Haifa, Israel

Hadassah Ein Karem Hospital

Jerusalem, Israel

Rabin MC

Petah Tikva, Israel

The Chaim Sheba Medical Center

Ramat Gan, Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Assuta Medical Centers

Tel Aviv, Israel

National Cancer Center

Goyang-si, South Korea

Samsung Medical Center

Seoul, South Korea

Seoul National University Hospital

Seoul, South Korea

Asan Medical Center

Seoul, South Korea

Severance Hospital

Seoul, South Korea

Hospital Universitario Vall d Hebron

Barcelona, Spain

Hospital Universitario Ramón y Cajal

Madrid, Spain

Centro Integral Oncológico Clara Campal Ensayos Clínicos START

Madrid, Spain

Hospital Clinico Universitario de Valencia

Valencia, Spain

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NCT04802759