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Trial record 22 of 31 for:    "Transitional Cell Carcinoma" | "Atezolizumab"

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 : November 1, 2019
Sponsor:
Collaborator:
Forty Seven Inc.,Tesaro Inc., Seattle Genetics and Astellas, Sanofi
Information provided by (Responsible Party):
Hoffmann-La Roche

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).

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Drug: Atezolizumab Drug: Enfortumab Vedotin Drug: Niraparib Drug: Hu5F9-G4 Drug: Isatuximab Drug: Linagliptin Drug: Tocilizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 305 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Locally Advanced or Metastatic Urothelial Carcinoma After Failure With Platinum-Containing Chemotherapy (MORPHEUS-mUC)
Actual Study Start Date : June 1, 2019
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : August 23, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Atezolizumab

For the control, + EV, + Nira, + Isa, 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.


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.
Drug: Atezolizumab

For the control, + EV, + Nira, + Isa, 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.

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.
Drug: Atezolizumab

For the control, + EV, + Nira, + Isa, 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: Niraparib
Niraparib will be administered at a dose of 200 mg once daily (QD) by mouth.

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.
Drug: Atezolizumab

For the control, + EV, + Nira, + Isa, 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: 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.

Experimental: Atezolizumab + Isatuximab
Participants will receive atezolizumab and Isatuximab (Isa) 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.
Drug: Atezolizumab

For the control, + EV, + Nira, + Isa, 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: Isatuximab
During Cycle 1 participants will receive isatuximab IV weekly (on Days 1, 8, and 15). For all subsequent cycles, isatuximab will be administered only on Day 1. Cycle = 21 days.

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.
Drug: Atezolizumab

For the control, + EV, + Nira, + Isa, 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: Linagliptin
Partcicpants will take one 5-mg tablet of linagliptin orally once a day (QD) during each 21-day cycle.

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.
Drug: Atezolizumab

For the control, + EV, + Nira, + Isa, 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: 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.




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Baseline until disease progression or loss of clinical benefit (approximately 4 years) ]

Secondary Outcome Measures :
  1. 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 ]
  2. Overall Survival (OS) [ Time Frame: Randomization to death from any cause, through the end of study (approximately 4 years) ]
  3. Overall Survival (at specific time-points) [ Time Frame: 12 months ]
  4. 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) ]
  5. Disease Control Rate (DCR) [ Time Frame: Baseline through end of study (approximately 4 years) ]
  6. Percentage of Participants with Adverse Events [ Time Frame: Baseline to end of study (approximately 4 years) ]
  7. 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. ]
  8. 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. ]
  9. 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. ]
  10. 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. ]
  11. 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. ]
  12. 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). ]
  13. 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. ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 agents that block CD38
  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03869190


Contacts
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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

Locations
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United States, California
UCLA Department of Medicine Recruiting
Los Angeles, California, United States, 90024
UCSF Comprehensive Cancer Ctr Not yet recruiting
San Francisco, California, United States, 94158
Stanford Cancer Center Not yet recruiting
Stanford, California, United States, 94305-5820
United States, Kentucky
Norton Cancer Institute Recruiting
Louisville, Kentucky, United States, 40202
France
Centre Francois Baclesse; Pharmacie Not yet recruiting
Caen, France, 14076
Centre Leon Berard Recruiting
Lyon, France, 69008
Institut régional du Cancer Montpellier Recruiting
Montpellier, France, 34298
Institut Claudius Regaud; Radiotherapie Recruiting
Toulouse, France, 31052
Gustave Roussy Cancer Campus Not yet recruiting
Villejuif, France, 94805
Greece
Alexandras General Hospital of Athens; Oncology Department Active, not recruiting
Athens, Greece, 115 28
Attiko Hospital University of Athens; 2Nd Dept. of Propaedeutic Medicine Not yet recruiting
Athens, Greece, 12462
University Hospital of Patras Medical Oncology Not yet recruiting
Patras, Greece, 265 04
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Asan Medical Center - Oncology Recruiting
Seoul, Korea, Republic of, 05505
Severance Hospital; Yonsei Cancer Center; Yonsei University College of Medicine Recruiting
Seoul, Korea, Republic of, 120-749
Spain
ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO Recruiting
L'Hospitalet de Llobregat, Barcelona, Spain, 08908
Complejo Hospitalario de Navarra Recruiting
Pamplona, Navarra, Spain, 31008
Vall d´Hebron Institute of Oncology (VHIO), Barcelona Recruiting
Barcelona, Spain, 08035
Hospital General Universitario Gregorio Mara Recruiting
Madrid, Spain, 28009
MD Anderson Cancer Center Recruiting
Madrid, Spain, 28033
Hospital Univ 12 de Octubre Recruiting
Madrid, Spain, 28041
START Madrid. Centro Integral Oncologico Clara Campal; CIOCC Recruiting
Madrid, Spain, 28050
United Kingdom
Barts and The London Recruiting
London, United Kingdom, EC1M 6BQ
The Christie NHS Foundation Trust Withdrawn
Manchester, United Kingdom, M20 4BX
Royal Marsden NHS Foundation Trust Recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Hoffmann-La Roche
Forty Seven Inc.,Tesaro Inc., Seattle Genetics and Astellas, Sanofi

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03869190     History of Changes
Other Study ID Numbers: WO39613
First Posted: March 11, 2019    Key Record Dates
Last Update Posted: November 1, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Atezolizumab
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Linagliptin
Niraparib
Hu5F9-G4
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Hypoglycemic Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors
Antineoplastic Agents, Immunological