Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic or Inoperable Locally Advanced Triple-Negative Breast Cancer (Morpheus-TNBC) (Morpheus-TNBC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03424005
Recruitment Status : Recruiting
First Posted : February 6, 2018
Last Update Posted : February 11, 2020
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE January 30, 2018
First Posted Date  ICMJE February 6, 2018
Last Update Posted Date February 11, 2020
Actual Study Start Date  ICMJE April 2, 2018
Estimated Primary Completion Date August 17, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 5, 2018)
Objective Response Rate (ORR) [ Time Frame: Baseline until disease progression or loss of clinical benefit ( approximately 4 years) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03424005 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2019)
  • Progression Free Survival (PFS) [ Time Frame: Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 4 years) as determined by the investigator according to RECIST v1.1 ]
  • Disease Control Rate (DCR) [ Time Frame: Baseline through end of study (approximately 4 years) ]
  • Overall Survival (OS) [ Time Frame: Randomization to death from any cause, through the end of study (approximately 4 years) ]
  • Overall Survival (at specific time-points) [ Time Frame: 12 and 18 months ]
  • Duration of Response (DOR) [ Time Frame: 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 (approximately 4 years) ]
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline to end of study (approximately 4 years) ]
  • Serum Concentration of Atezolizumab [ Time Frame: Day 1, Cycle 1 pre-treatment and 30 mins post-infusion; Day 1 of Cycles 2,3,4,8,12, and 16 pre-treatment (Cycles = 21 or 28 days); through end of study (~ 4 years); 120 days after last dose ]
  • Plasma Concentration of Ipatasertib [ Time Frame: Day 15, Cycle 1 pre treatment and 1-3 hours after Ipatasertib dose (Cycle = 28 days); ]
  • Plasma or Serum Concentration of SGN-LIV1A [ Time Frame: Day 1 Cycle, 1 pre-treatment and 30 minutes after SGN-LIV1A infusion (Cycle = 21 days). ]
  • Plasma Concentration of Cobimetinib [ Time Frame: Day 15, Cycle 1 Pre- Cobimetinib dose and 2-4 hours after Cobimetinib dose (Cycle = 28 days). ]
  • Plasma Concentration of Capecitabine [ Time Frame: Day 1, Cycle 1, 2 hours after capecitabine dose (Cycle = 21 days). ]
  • Serum Concentration of RO6874281 [ Time Frame: From pre-treatment on Cycle 1 Day 1 (Cycle = 21 days), though to end of study (~ 4 years, see Description for specific timings). ]
    Pre-treatment and at end of infusion on Day 1 of Cycles 1, 2, 3, 4, 6, 8, 10, 12, 14, 16 and 19 and every third cycle thereafter; 1, 2 and 4 hours after start of infusion on Day 1 of Cycles 1 and 3; 24 hours, 48 hours and 168 hours after infusion on Days 2, 3 and 8 of Cycle 1 and 3 (Cycle = 21 days); through end of study (~ 4 years).
  • Serum Concentration of Selicrelumab [ Time Frame: Pre-treatment on Day 1 of Cycles 1, 2, 4, 8, 12, and 16 (Cycle = 28 days). ]
  • Serum Concentration of Bevacizumab [ Time Frame: Pre-treatment on Day 1 of Cycles 1 and 4 (Cycles = 21 or 28 days). ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 5, 2018)
  • Progression Free Survival (PFS) [ Time Frame: Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 4 years) as determined by the investigator according to RECIST v1.1 ]
  • Disease Control Rate (DCR) [ Time Frame: Baseline through end of study (approximately 4 years) ]
  • Overall Survival (OS) [ Time Frame: Randomization to death from any cause, through the end of study (approximately 4 years) ]
  • Overall Survival (at specific time-points) [ Time Frame: 12 and 18 months ]
  • Duration of Response (DOR) [ Time Frame: 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 (approximately 4 years) ]
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline to end of study (approximately 4 years) ]
  • Serum Concentration of Atezolizumab [ Time Frame: Day 1, Cycle 1 pre-treatment and 30 mins post-infusion; Day 1 of Cycles 2,3,4,8,12, and 16 pre-treatment; through end of study (~ 4 years); 120 days after last dose ]
  • Plasma Concentration of Ipatasertib [ Time Frame: Day 15, Cycle 1 pre treatment and 1-3 hours after Ipatasertib dose; ]
  • Plasma or Serum Concentration of SNG-LIV1A [ Time Frame: Day 1 Cycle, 1 pre-treatment and 30 minutes after SGN-LIV1A infusion ]
  • Plasma Concentration of Cobimetinib [ Time Frame: Day 15, Cycle 1 Pre- Cobimetinib dose and 2-4 hours after Cobimetinib dose ]
  • Plasma Concentration of Capecitabine [ Time Frame: Day 1, Cycle 1, 2 hours after capecitabine dose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic or Inoperable Locally Advanced Triple-Negative Breast Cancer (Morpheus-TNBC)
Official Title  ICMJE 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)
Brief 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 or inoperable locally advanced 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Cancer
Intervention  ICMJE
  • Drug: Capecitabine
    Capecitabine will be administered 1250 mg/m2 orally twice daily on Days 1−14, of each 21 day cycle
  • Drug: Atezolizumab

    For Atezolizumab + SGN-LIV1A, Bevacizumab, Capecitabine, RO6874281 or Chemo arms: Atezolizumab will be administered by IV, 1200 mg, on Day 1 of each 21-day cycle.

    For Atezolizumab + Bevacizumab+ Cobimetinib, + Selicrelumab + Bevacizumab, or + Ipatasertib arms: Atezolizumab will be administered by IV, 840 mg on Days 1 and 15, of each 28 day cycle

  • Drug: Ipatasertib
    Ipatasertib will be administered by mouth 400 mg once a day, on Day 1-21 of each 28 day cycle
  • Drug: SGN-LIV1A
    SGN-LIV1A will be administered by IV, 2.5 mg/kg (maximum calculated dose 250 mg), on Day 1 of each 21 day cycle
  • Drug: Bevacizumab
    When given as a doublet combination, Bevacizumab will be administered by IV, 15 mg/kg, on Day 1 of each 21 day cycle. When given as a triplet combination, Bevacizumab will be administered by IV, 10 mg/kg, on Days 1 and 15 of each 28 day cycle.
  • Drug: Cobimetinib
    Cobimetinib will be administered orally, once per day, 60 mg, on Days 1-21 of a 28-day cycle.
  • Drug: Chemotherapy (Gemcitabine + Carboplatin or Eribulin)

    Gemcitabine will be administered by IV, 1000 mg/m2, along with Carboplatin, by IV, AUC 2, on Days 1 and 8 of each 21 day cycle

    Or

    Eribulin will be administered by IV, 1.4 mg/m2 on days 1 and 8 of each 21 day cycle

  • Drug: RO6874281
    RO6874281 will be administered at a fixed dose of 10 mg IV on Day 1 of each 21 day cycle.
  • Drug: Selicrelumab
    Selicrelumab will be administered by SC injection at a fixed dose of 16 mg on Day 1 of Cycles 1 to 4 and every third cycle thereafter (cycle = 28 days).
Study Arms  ICMJE
  • Active Comparator: Capecitabine

    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

    Intervention: Drug: Capecitabine
  • Experimental: Atezolizumab + Ipatasertib

    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

    Interventions:
    • Drug: Atezolizumab
    • Drug: Ipatasertib
  • Experimental: Atezolizumab + SGN-LIV1A

    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

    Interventions:
    • Drug: Atezolizumab
    • Drug: SGN-LIV1A
  • Experimental: Atezolizumab + Bevacizumab
    Participants will receive doublet combination treatment with atezolizumab plus 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
    Interventions:
    • Drug: Atezolizumab
    • Drug: Bevacizumab
  • Experimental: Atezolizumab + Bevacizumab + Cobimetinib

    Participants will receive doublet combination treatment with atezolizumab + Bevacizumab + Cobimetinib 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

    Interventions:
    • Drug: Atezolizumab
    • Drug: Bevacizumab
    • Drug: Cobimetinib
  • Experimental: Atezolizumab + Capecitabine

    Participants will receive doublet combination treatment with atezolizumab + Capecitabine 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

    Interventions:
    • Drug: Capecitabine
    • Drug: Atezolizumab
  • Experimental: Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin)
    Participants will 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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Chemotherapy (Gemcitabine + Carboplatin or Eribulin)
  • Experimental: Atezolizumab + RO6874281

    Participants will receive doublet combination treatment with atezolizumab plus RO6874281 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.

    Interventions:
    • Drug: Atezolizumab
    • Drug: RO6874281
  • Experimental: Atezolizumab + Selicrelumab + Bevacizumab

    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.

    Interventions:
    • Drug: Atezolizumab
    • Drug: Bevacizumab
    • Drug: Selicrelumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 25, 2019)
310
Original Estimated Enrollment  ICMJE
 (submitted: February 5, 2018)
260
Estimated Study Completion Date  ICMJE August 17, 2021
Estimated Primary Completion Date August 17, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria Stage 1

  • ECOG Performance Status of 0 or 1
  • Metastatic or inoperable locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
  • Radiologic/objective evidence of recurrence or disease progression after chemotherapy for a total of one line of therapy for inoperable locally advanced or metastatic breast cancer
  • 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
  • Life expectancy =/> 3 months, as determined by the investigator
  • Tumor accessible for biopsy
  • 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
  • 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 test
  • Negative total hepatitis B core antibody (HBcAb)
  • Negative hepatitis C virus (HCV) antibody test at screening
  • Measurable disease (at least one target lesion)

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)

Exclusion Criteria for Stage 1

  • Prior treatment with any of the Stage 1 protocol-specified study treatments included in arms that are open at the time of screening, with the exception of capecitabine
  • 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
  • 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
  • Additional drug-specific exclusion criteria might apply.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID Number: CO40115 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com
Listed Location Countries  ICMJE Australia,   France,   Germany,   Korea, Republic of,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03424005
Other Study ID Numbers  ICMJE CO40115
2017-002038-21 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Seattle Genetics, Inc.
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP