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BRIEF TITLE: 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)

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)


  • Org Study ID: WO39613
  • Secondary ID:
  • NCT ID: NCT03869190
  • NCT Alias:
  • Sponsor: Hoffmann-La Roche - Industry
  • Source: 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.

Overal Status Start Date Phase Study Type
Recruiting June 1, 2019 Phase 1/Phase 2 Interventional

Primary Outcomes:

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

Primary Outcome 1 - Time Frame: 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 - Time Frame: Randomization to approximately 4 years

Condition:

  • Urothelial Carcinoma
  • Bladder Cancer

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

- 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.
Show More

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Name: Reference Study ID Number: WO39613 www.roche.com/about_roche/roche_worldwide.htm

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

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

Locations

Facility Status Contact
UCLA Department of Medicine
Los Angeles, California 90024
United States
Recruiting
UCSF Comprehensive Cancer Ctr
San Francisco, California 94158
United States
Recruiting
Stanford Cancer Center
Stanford, California 94305-5820
United States
Recruiting
University of Kentucky Chandler Medical Center
Lexington, Kentucky 40504
United States
Not yet recruiting
Norton Cancer Institute
Louisville, Kentucky 40202
United States
Recruiting
Levine Cancer Institute
Charlotte, North Carolina 28204
United States
Not yet recruiting
Cleveland Clinic
Cleveland, Ohio 44195
United States
Not yet recruiting
Centre Francois Baclesse; Pharmacie
Caen, 14076
France
Recruiting
Centre Leon Berard
Lyon, 69008
France
Recruiting
Institut régional du Cancer Montpellier
Montpellier, 34298
France
Recruiting
Institut Claudius Regaud; Radiotherapie
Toulouse, 31052
France
Recruiting
Gustave Roussy Cancer Campus
Villejuif, 94805
France
Recruiting
Alexandras General Hospital of Athens; Oncology Department
Athens, 115 28
Greece
Completed
Attiko Hospital University of Athens; 2Nd Dept. of Propaedeutic Medicine
Athens, 12462
Greece
Recruiting
Athens Medical Center; Dept. of Oncology
Athens, 151 25
Greece
Not yet recruiting
University Hospital of Patras Medical Oncology
Patras, 265 04
Greece
Withdrawn
Seoul National University Hospital
Seoul, 03080
Korea, Republic of
Recruiting
Asan Medical Center
Seoul, 05505
Korea, Republic of
Recruiting
Severance Hospital; Yonsei Cancer Center; Yonsei University College of Medicine
Seoul, 120-749
Korea, Republic of
Recruiting
ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO
L'Hospitalet de Llobregat, Barcelona 08908
Spain
Recruiting
Complejo Hospitalario Universitario de Santiago (CHUS) ; Intermedios y Urgencias Pediatricas
Santiago de Compostela, LA Coruña 15706
Spain
Not yet recruiting
Clinica Universitaria de Navarra
Pamplona, Navarra 31008
Spain
Recruiting
Hospital del Mar
Barcelona, 08003
Spain
Not yet recruiting
Vall d´Hebron Institute of Oncology (VHIO), Barcelona
Barcelona, 08035
Spain
Recruiting
Hospital Clinic de Barcelona; Neurologia
Barcelona, 08036
Spain
Not yet recruiting
Hospital Universitario Reina Sofia
Cordoba, 14004
Spain
Not yet recruiting
Hospital General Universitario Gregorio Mara
Madrid, 28009
Spain
Recruiting
MD Anderson Cancer Center
Madrid, 28033
Spain
Recruiting
Hospital Universitario Fundacion Jimenez Diaz.
Madrid, 28040
Spain
Not yet recruiting
Hospital Univ 12 de Octubre
Madrid, 28041
Spain
Recruiting
START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
Madrid, 28050
Spain
Recruiting
Hospital Clinico Universitario de Valencia
Valencia, 46010
Spain
Not yet recruiting
Barts and The London
London, EC1M 6BQ
United Kingdom
Recruiting
The Christie NHS Foundation Trust
Manchester, M20 4BX
United Kingdom
Withdrawn
Churchill Hospital; Pharmacy Clinical Trials Office, Pharmacy Department
Oxford, OX3 7LJ
United Kingdom
Not yet recruiting
Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT
United Kingdom
Recruiting