Back to Clinical Trials

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

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC)

INTRODUCTION

  • Org Study ID: WO39613
  • Secondary ID: N/A
  • NTC ID: NCT03869190
  • Sponsor: Hoffmann-La Roche

BRIEF SUMMARY

A Phase Ib/II, open-label, multicenter, randomized, umbrella study in participants with cisplatin-ineligible 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.

  • Overall Status
    Recruiting
  • Start Date
    June 1, 2019
  • Phase
    Phase 1, Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Objective Response Rate (ORR) for mUC Cohort Stage 1

Primary Outcome 1 - Timeframe: Baseline until disease progression or loss of clinical benefit (approximately 4 years)

Primary Outcome 2 - Measure: pCR for Muscle Invasive Bladder Cancer (MIBC) Cohorts

Primary Outcome 2 - Timeframe: Randomization to approximately 4 years

CONDITION

  • Urothelial Carcinoma
  • Bladder Cancer

ELIGIBILITY

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

- Patients who refuse neoadjuvant cisplatin-based chemotherapy or in whom neoadjuvant cisplatin-based therapy is not appropriate

- 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:
Patients will be excluded from the Atezo + Tira arm within the MIBC Cohorts if they meet any of the additional criteria for that arm.

- 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 in the MIBC Cohorts:
- Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening
Additional Exclusion Criteria for Atezo+RO7122290 Arm in the MIBC Cohorts:
- Clinically significant cardiovascular or cerebrovascular disease within 6 months prior to Day 1 of study drug administration will be excluded.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 888-662-6728 (U.S. Only)

Email: global-roche-genentech-trials@gene.com

LOCATION

Facility Status Contact
Facility: UCLA Department of Medicine
Los Angeles, California 90024
United States
Status: Recruiting Contact: N/A
Facility: UCSF Comprehensive Cancer Ctr
San Francisco, California 94158
United States
Status: Recruiting Contact: N/A
Facility: Stanford Cancer Center
Stanford, California 94305-5820
United States
Status: Recruiting Contact: N/A
Facility: Norton Cancer Institute
Louisville, Kentucky 40202
United States
Status: Recruiting Contact: N/A
Facility: Cleveland Clinic
Cleveland, Ohio 44195
United States
Status: Recruiting Contact: N/A
Facility: Centre Francois Baclesse; Pharmacie
Caen, Barcelona 14076
France
Status: Recruiting Contact: N/A
Facility: Centre Leon Berard
Lyon, LA Coruña 69008
France
Status: Recruiting Contact: N/A
Facility: Institut régional du Cancer Montpellier
Montpellier, Navarra 34298
France
Status: Recruiting Contact: N/A
Facility: Institut Claudius Regaud; Radiotherapie
Toulouse, 31052
France
Status: Recruiting Contact: N/A
Facility: Gustave Roussy Cancer Campus
Villejuif, 94805
France
Status: Recruiting Contact: N/A
Facility: Attiko Hospital University of Athens; 2Nd Dept. of Propaedeutic Medicine
Athens, 12462
Greece
Status: Recruiting Contact: N/A
Facility: Seoul National University Hospital
Seoul, 03080
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Asan Medical Center
Seoul, 05505
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Severance Hospital; Yonsei Cancer Center; Yonsei University College of Medicine
Seoul, 120-749
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO
L'Hospitalet de Llobregat, 08908
Spain
Status: Recruiting Contact: N/A
Facility: Clinica Universitaria de Navarra
Pamplona, 31008
Spain
Status: Recruiting Contact: N/A
Facility: Vall d´Hebron Institute of Oncology (VHIO), Barcelona
Barcelona, 08035
Spain
Status: Recruiting Contact: N/A
Facility: Hospital General Universitario Gregorio Mara
Madrid, 28009
Spain
Status: Recruiting Contact: N/A
Facility: MD Anderson Cancer Center
Madrid, 28033
Spain
Status: Recruiting Contact: N/A
Facility: Hospital Univ 12 de Octubre
Madrid, 28041
Spain
Status: Recruiting Contact: N/A
Facility: START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
Madrid, 28050
Spain
Status: Recruiting Contact: N/A
Facility: Hospital Clinico Universitario de Valencia
Valencia, 46010
Spain
Status: Recruiting Contact: N/A
Facility: Barts and The London
London, EC1M 6BQ
United Kingdom
Status: Recruiting Contact: N/A
Facility: Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT
United Kingdom
Status: Recruiting Contact: N/A