Summary

for people ages 18 years and up (full criteria)
at La Jolla, California and other locations
study started
estimated completion:

Description

Summary

This is a Phase Ib/II, open-label, multicenter, randomized umbrella study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations in patients with metastatic TNBC who had disease progression during or following first-line metastatic treatment with chemotherapy. The study will be performed in two stages. During Stage 1, participants will be randomized to capecitabine (control) or an atezolizumab-containing doublet or triplet combination. Those who experience disease progression, loss of clinical benefit, or unacceptable toxicity may be eligible to receive a new doublet combination treatment in Stage 2 until loss of clinical benefit or unacceptable toxicity. New treatment arms may be added and/or existing treatment arms may be closed during the course of the study on the basis of ongoing clinical efficacy and safety as well as the current treatments available.

Official Title

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

Keywords

Triple Negative Breast Cancer Breast Neoplasms Triple Negative Breast Neoplasms Gemcitabine Capecitabine Atezolizumab Bevacizumab Carboplatin Antibodies, Monoclonal Immunoconjugates Ipatasertib SGN-LIV1A Cobimetinib Chemotherapy (Gemcitabine + Carboplatin or Eribulin) Atezolizumab + Ipatasertib Atezolizumab + SGN-LIV1A Atezolizumab + Bevacizumab Atezolizumab + Bevacizumab + Cobimetinib Atezolizumab + Capecitabine

Eligibility

You can join if…

Open to people ages 18 years and up

Stage 1

  • ECOG Performance Status of 0 or 1
  • Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER,and PR expression)
  • Radiologic/objective evidence of recurrence or disease progression after one line of chemotherapy for metastatic breast cancer MBC
  • Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing
  • Eligible for capecitabine monotherapy
  • Adequate hematologic and end-organ function, laboratory test results, obtained within 14 days prior to initiation of study treatment.
  • Negative HIV test at screening
  • Negative hepatitis B surface antigen .
  • Negative hepatitis C virus (HCV) antibody test at screening or positive HCV antibody test followed by a negative HCV RNA test at screening

Inclusion Criteria for Stage 1 and Stage 2

  • Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1(RECIST v1.1)
  • Tumor accessible for biopsy
  • For patients receiving therapeutic anticoagulation: stable anticoagulant regimen during the 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 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

Inclusion criteria stage 2

  • ECOG Performance Status of 0, 1, or 2
  • Patients randomly allocated to the control arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity, provided that Medical Monitor approval for entry into Stage 2 is obtained, or disease progression per RECIST v1.1 while receiving control treatment
  • Patients randomly allocated to an experimental arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab, disease progression per RECIST v1.1, or loss of clinical benefit as determined by the investigator (see Section 3.1.1.1 for details) while receiving Stage 1 treatment
  • Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible by the investigator)

You CAN'T join if...

for Stage 1

  • Prior treatment with any of the protocol-specified study treatments
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Inability to swallow medication or malabsorption condition that would alter the absorption of orally administered medications
  • Treatment with sorivudine or its chemically related analogues, such as brivudine
  • History of severe and unexpected reactions to fluoropyrimidine therapy

Exclusion Criteria for Stage 1 and Stage 2

  • 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 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

Locations

  • University of California San Diego Medical Center; Moores Cancer Center not yet accepting patients
    La Jolla California 92093 United States
  • The West Clinic; West Cancer Center accepting new patients
    Germantown Tennessee 38138 United States
  • H. Lee Moffitt Cancer Center and Research Inst. not yet accepting patients
    Tampa Florida 33612 United States
  • University of Pittsburgh Medical Center accepting new patients
    Pittsburgh Pennsylvania 15213 United States
  • Thomas Jefferson University Hospital not yet accepting patients
    Philadelphia Pennsylvania 19107 United States
  • Rutgers Cancer Institute of New Jersey not yet accepting patients
    New Brunswick New Jersey 08901 United States
  • Hackensack Univ Medical Center; John Theurer Cancer Ctr accepting new patients
    Hackensack New Jersey 07601 United States
  • NYU Langone Medical Center; NYU Perlmutter Cancer Center accepting new patients
    New York New York 10016 United States
  • Beatson West of Scotland Cancer Centre not yet accepting patients
    Glasgow G12 0YN United Kingdom
  • Barts Health NHS Trust - St Bartholomew's Hospital not yet accepting patients
    London EC1A 7BE United Kingdom
  • Centre Léon Bérard not yet accepting patients
    Lyon 69008 France
  • Institut Universitaire du Cancer de Toulouse-Oncopole not yet accepting patients
    Toulouse 31059 France
  • Gustave Roussy not yet accepting patients
    Villejuif CEDEX 94800 France
  • Universitätsklinikum Erlangen; Frauenklinik not yet accepting patients
    Erlangen 91054 Germany
  • Universitätsklinikum Essen not yet accepting patients
    Essen 45147 Germany
  • Vall d´Hebron Institute of Oncology (VHIO), Barcelona not yet accepting patients
    Barcelona 08035 Spain
  • Hospital Universitario Ramón y Cajal not yet accepting patients
    Madrid 28034 Spain
  • Centro Integral Oncológico Clara Campal Ensayos Clínicos START not yet accepting patients
    Madrid 28050 Spain
  • Seoul National University Hospital not yet accepting patients
    Seoul 03080 Korea, Republic of
  • Severance Hospital not yet accepting patients
    Seoul 03722 Korea, Republic of
  • University of Ulsan College of Medicine - Asan Medical Center not yet accepting patients
    Seoul 05505 Korea, Republic of
  • Peter MacCallum Cancer Centre-East Melbourne not yet accepting patients
    Melbourne Victoria 3000 Australia

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Hoffmann-La Roche
ID
NCT03424005
Phase
Phase 1/2
Study Type
Interventional
Last Updated
June 8, 2018