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Trial record 1 of 1 for:    MORPHEUS-mUC
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A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-based Treatment Combinations in Patients With Locally Advanced or Metastatic Urothelial Carcinoma After Failure With Platinum-Containing Chemotherapy (MORPHEUS mUC)

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ClinicalTrials.gov Identifier: NCT03869190
Recruitment Status : Recruiting
First Posted : March 11, 2019
Last Update Posted : July 16, 2020
Sponsor:
Collaborator:
Forty Seven Inc.,Tesaro Inc., Seattle Genetics and Astellas
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE March 8, 2019
First Posted Date  ICMJE March 11, 2019
Last Update Posted Date July 16, 2020
Actual Study Start Date  ICMJE June 1, 2019
Estimated Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 8, 2019)
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
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2020)
  • 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 1.1 ]
  • 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 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) ]
  • Disease Control Rate (DCR) [ Time Frame: Baseline through end of study (approximately 4 years) ]
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline to end of study (approximately 4 years) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 8, 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 1.1 ]
  • 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 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) ]
  • Disease Control Rate (DCR) [ Time Frame: Baseline 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, 4, 8, 12, and 16 pre-treatment (Cycles = 21 or 28 days); within 30 days after last dose. ]
  • Serum and Plasma Concentration of Enfortumab Vedotin [ Time Frame: Day 1, Cycle 1 pre-treatment and at end of infusion; Day 8 Cycle 1 pre-treatment; Day 1 of Cycles 2, 4, 8, 12 and 16 pre-treatment (Cycles = 21 days); within 30 days after last dose. ]
  • Plasma Concentration of Niraparib [ Time Frame: Day 1, Cycle 1 pre-treatment and 2 hours after administration; Day 1 of Cycle 4, 2 hours after administration (Cycle = 21 days); within 30 days after last dose. ]
  • Serum Concentration of Hu5F9-G4 [ Time Frame: Day 1 and 8, Cycle 1 pre-treatment and 1 hour after infusion; Day 22 of Cycle 1 pre-treatment; Day 1 of Cycles 2, 4 8 and 16 (Cycle = 28 days); within 30 days after last dose. ]
  • Plasma Concentration of Isatuximab [ Time Frame: Day 1, Cycles 1 and 4 pre-treatment and at end of infusion; Day 1 of Cycles 2, 6, 8, 10, 12 and 16 pre-treatment (Cycle = 21 days); within 30 days after last dose. ]
  • Plasma Concentration of Linagliptin [ Time Frame: Day 1, Cycle 1, 2 hours after administration; Day 15, Cycle 1 pre-treatment; Day 1 Cycle 2, pre-treatment (Cycle = 21 days). ]
  • Serum Concentration of Tocilizumab [ Time Frame: Day 1, Cycle 1 pre-treatment and at end of infusion; Day 1 of Cycles 2, 4, 6, 8, 10, 12, 14, 16 and every fourth cycle thereafter, pre-treatment (Cycles = 28 days); within 30 days after last 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 Locally Advanced or Metastatic Urothelial Carcinoma After Failure With Platinum-Containing Chemotherapy
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 Locally Advanced or Metastatic Urothelial Carcinoma After Failure With Platinum-Containing Chemotherapy (MORPHEUS-mUC)
Brief Summary A Phase Ib/II, open-label, multicenter, randomized, umbrella study in participants with locally advanced or metastatic Urothelial Carcinoma (UC) who have progressed during or following a platinum-containing regimen. 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 participant population (e.g., with regard to prior anti-cancer treatment or biomarker status).
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 Urothelial Carcinoma
Intervention  ICMJE
  • Drug: Atezolizumab

    For the control, + EV, + Nira, + Tira, and + Lina arms, Atezolizumab will be administered intravenously (IV) at a fixed dose of 1200 mg every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

    For the Atezo + Hu5F9-G4 and + TCZ arms, Atezo will be administered IV at a fixed dose of 840 mg every 2 weeks (Q2W) on Days 1 and 15 of each 28-day cycle.

  • Drug: Enfortumab Vedotin
    Enfortumab vedotin will be administered at a dose of 1.25 mg/kg IV on Days 1 and 8 of each 21-day cycle.
  • Drug: Niraparib
    Niraparib will be administered at a dose of 200 mg once daily (QD) by mouth.
  • Drug: Hu5F9-G4
    Participants will receive an 1-mg/kg priming dose IV on Day 1 followed by three weekly IV doses of 30 mg/kg on Days 8, 15, and 22. During Cycle 2, participants will receive weekly IV doses of 30 mg/kg on Days 1, 8, 15, and 22. For all subsequent cycles, participants will receive 30 mg/kg on Days 1 and 15. Cycle = 28 days.
  • Drug: Tiragolumab
    Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21-day cycle.
  • Drug: Linagliptin
    Participants will take one 5-mg tablet of linagliptin orally once a day (QD) during each 21-day cycle.
  • Drug: Tocilizumab
    Tocilizumab will be administered by IV infusion at a dose of 8 mg/kg every 4 weeks (Q4W) on Day 1 of each 28-day cycle.
Study Arms  ICMJE
  • Active Comparator: Atezolizumab
    Participants will receive atezolizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
    Intervention: Drug: Atezolizumab
  • Experimental: Atezolizumab + Enfortumab Vedotin
    Participants will receive atezolizumab and Enfortumab Vedotin (EV) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Enfortumab Vedotin
  • Experimental: Atezolizumab + Niraparib
    Participants will receive atezolizumab and Niraparib (Nira) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Niraparib
  • Experimental: Atezolizumab + Hu5F9-G4
    Participants will receive atezolizumab and Hu5F9-G4 until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Hu5F9-G4
  • Experimental: Atezolizumab + Tiragolumab
    Participants will receive atezolizumab and Tiragolumab (Tira) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Tiragolumab
  • Experimental: Atezolizumab + Linagliptin
    Participants will receive atezolizumab and Linagliptin (Lina) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Linagliptin
  • Experimental: Atezolizumab + Tocilizumab
    Participants will receive atezolizumab and Tocilizumab (TCZ) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Tocilizumab
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: March 8, 2019)
305
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 10, 2021
Estimated Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically documented, locally advanced or metastatic UC (also termed TCC or urothelial cell carcinoma of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra)
  • Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status by means of central testing
  • Disease progression during or following treatment with no more than one platinum-containing regimen for inoperable, locally advanced or metastatic UC or disease recurrence
  • ECOG Performance Status of 0 or 1
  • Measurable disease (at least one target lesion) according to RECIST v1.1
  • Adequate hematologic and end-organ function
  • Negative HIV test at screening
  • Negative total hepatitis B core antibody (HBcAb) test and hepatitis C virus (HCV) antibody at screening
  • Tumor accessible for biopsy
  • For women of childbearing potential: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating eggs
  • For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

  • Prior treatment with a T-cell co-stimulating therapy or a CPI including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Prior treatment with any of the protocol-specified study treatments including treatment with poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, nectin-4 targeting agents, signal regulatory protein alpha-targeting agents, or TIGIT-targeting agents
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
  • Eligibility only for the control arm
  • Prior allogeneic stem cell or solid organ transplantation
  • Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initiation of study treatment
  • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Uncontrolled tumor-related pain
  • Uncontrolled or symptomatic hypercalcemia
  • 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, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
  • History of malignancy other than UC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
  • 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
  • Uncontrolled hypertension
  • Grade 3 or greater hemorrhage or bleeding event within 28 days prior to initiation of study treatment
  • Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment
  • 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: WO39613 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com
Listed Location Countries  ICMJE France,   Greece,   Korea, Republic of,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03869190
Other Study ID Numbers  ICMJE WO39613
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 Forty Seven Inc.,Tesaro Inc., Seattle Genetics and Astellas
Investigators  ICMJE Not Provided
PRS Account Hoffmann-La Roche
Verification Date July 2020

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