Clinical trial NCT03424005: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Gilead Sciences
First posted: 2018-02-06
Enrollment: 580
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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
* 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

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
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* 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
* 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
* Eligibility only for the control arm

Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort)

* 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
* 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
* Pregnancy or breastfeeding, or intention of becoming pregnant during the study

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Baseline until disease progression or loss of clinical benefit (up to approximately 10 years)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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
measure: Disease Control Rate (DCR)
timeFrame: Baseline through end of study (up to approximately 10 years)
measure: Overall Survival (OS)
timeFrame: Randomization to death from any cause, through the end of study (up to approximately 10 years)
measure: Overall Survival (at specific time-points)
timeFrame: 12 and 18 months
measure: Duration of Response (DOR)
timeFrame: 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)
measure: Percentage of Participants with Adverse Events
timeFrame: Baseline to end of study (up to approximately 10 years)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: University of California San Diego Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Longmont
country: United States
facility: Rocky Mountain Cancer Center - Longmont
state: Colorado
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Inst.
state: Florida
city: Hackensack
country: United States
facility: Hackensack Univ Medical Center
state: New Jersey
city: Howell
country: United States
facility: Regional Cancer Care Associates, LLC
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Germantown
country: United States
facility: The West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Plano
country: United States
facility: Texas Oncology-Plano East
state: Texas
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre-East Melbourne
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital - Medical Oncology
state: Western Australia
city: Lyon
country: France
facility: Centre Léon Bérard
city: Montpellier
country: France
facility: Institut régional du Cancer Montpellier
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse-Oncopole
city: Villejuif CEDEX
country: France
facility: Gustave Roussy
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Medical Center
city: Petach Tikva
country: Israel
facility: Rabin MC
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Tel Aviv
country: Israel
facility: Assuta Medical Centers
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center Clinical Trials Center / Center for Breast Cancer
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: University of Ulsan College of Medicine - Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal Ensayos Clínicos START
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Barts Health NHS Trust - St Bartholomew's Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: