Bladder Cancer Clinical Trial

Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC)

Summary

A Phase Ib/II, open-label, multicenter, randomized, umbrella study in participants with MIBC and 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). Participants in the mUC Cohort who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen for Stage 2.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria for mUC Cohort:

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

Inclusion Criteria for MIBC Cohorts:

ECOG PS of 0 or 1
Fit and planned-for cystectomy
Histologically documented MIBC (pT2-4, N0, M0), also termed TCC or urothelial cell carcinoma of the urinary bladder
N0 or M0 disease by CT or MRI
Adequate hematologic and end-organ function
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from 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 mUC Cohort:

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, Trop-2 targeting agents, FAP-directed therapies, 4-1BB (CD137)-directed therapies, or topoisomerase 1 inhibitors
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

Exclusion for MIBC Cohorts:

Prior treatment with systemic immunostimulatory agents prior to the initiation of study treatment
Eligibility only for the control arm
Prior allogeneic stem cell or solid organ transplantation
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, with the following exceptions: Patients who received acute, low-dose, systemic immunosuppressant medications, or a one-time pulse dose of systemic immunosuppressant medication are eligible for the study after Medical Monitor approval has been obtained. Patients who received mineralocorticoids, corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
Severe infection within 4 weeks prior to initiation of study treatment
Pregnancy or breastfeeding, or intention of becoming pregnant during the study

Additional Exclusion Criteria for Atezo+Tira and Atezo (Atezolizumab) +Tira+Cis (Cisplatin)+Gem (Gemcitabine) in the MIBC Cohorts:

- Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening.

Additional Exclusion Criteria for the Cisplatin-Eligible MIBC Cohort:

Patients who decline neoadjuvant cisplatin-based chemotherapy or in whom neoadjuvant cisplatin-based therapy is not appropriate.
Impaired renal function.

Study is for people with:

Bladder Cancer

Phase:

Phase 1

Estimated Enrollment:

645

Study ID:

NCT03869190

Recruitment Status:

Recruiting

Sponsor:

Hoffmann-La Roche

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There are 39 Locations for this study

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UCLA Department of Medicine
Los Angeles California, 90024, United States
UCSF Comprehensive Cancer Ctr
San Francisco California, 94158, United States
Stanford Cancer Center
Stanford California, 94305, United States
University of Kentucky Chandler Medical Center
Lexington Kentucky, 40536, United States
Norton Cancer Institute
Louisville Kentucky, 40202, United States
Levine Cancer Institute
Charlotte North Carolina, 28204, United States
Cleveland Clinic
Cleveland Ohio, 44195, United States
Centre Francois Baclesse; Pharmacie
Caen , 14076, France
Centre Leon Berard
Lyon , 69008, France
Institut régional du Cancer Montpellier
Montpellier , 34298, France
Institut Claudius Regaud; Radiotherapie
Toulouse , 31052, France
Gustave Roussy Cancer Campus
Villejuif , 94805, France
Alexandras General Hospital of Athens; Oncology Department
Athens , 115 2, Greece
Attiko Hospital University of Athens; 2Nd Dept. of Propaedeutic Medicine
Athens , 12462, Greece
Athens Medical Center; Dept. of Oncology
Athens , 151 2, Greece
University Hospital of Patras Medical Oncology
Patras , 265 0, Greece
Seoul National University Hospital
Seoul , 03080, Korea, Republic of
Asan Medical Center
Seoul , 05505, Korea, Republic of
Severance Hospital; Yonsei Cancer Center; Yonsei University College of Medicine
Seoul , 120-7, Korea, Republic of
ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO
L'Hospitalet de Llobregat Barcelona, 08908, Spain
Complejo Hospitalario Universitario de Santiago (CHUS) ; Intermedios y Urgencias Pediatricas
Santiago de Compostela LA Coruña, 15706, Spain
Clinica Universitaria de Navarra
Pamplona Navarra, 31008, Spain
Hospital del Mar
Barcelona , 08003, Spain
Vall d´Hebron Institute of Oncology (VHIO), Barcelona
Barcelona , 08035, Spain
Hospital Clinic i Provincial; Servicio de Neurologia
Barcelona , 08036, Spain
Hospital Universitario Reina Sofia
Cordoba , 14008, Spain
Hospital General Universitario Gregorio Mara
Madrid , 28009, Spain
MD Anderson Cancer Center
Madrid , 28033, Spain
Hospital Universitario Fundacion Jimenez Diaz.
Madrid , 28040, Spain
Hospital Univ 12 de Octubre
Madrid , 28041, Spain
START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
Madrid , 28050, Spain
Hospital Clinico Universitario de Valencia
Valencia , 46010, Spain
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City , 807, Taiwan
National Cheng Kung University Hospital
Tainan , 70457, Taiwan
Taipei Veterans General Hospital
Taipei City , 112, Taiwan
Barts and The London
London , EC1M , United Kingdom
The Christie NHS Foundation Trust
Manchester , M20 4, United Kingdom
Churchill Hospital; Pharmacy Clinical Trials Office, Pharmacy Department
Oxford , OX3 7, United Kingdom
Royal Marsden NHS Foundation Trust
Sutton , SM2 5, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Bladder Cancer

Phase:

Phase 1

Estimated Enrollment:

645

Study ID:

NCT03869190

Recruitment Status:

Recruiting

Sponsor:


Hoffmann-La Roche

How clear is this clinincal trial information?

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