Clinical trial NCT03029832: A Study of MOXR0916 in Combination With Atezolizumab Versus Atezolizumab Alone in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Therapy
Official title: A Phase II, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of MOXR0916 in Combination With Atezolizumab Versus Atezolizumab Alone in Patients With Untreated Locally Advanced or Metastatic Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Urothelial Carcinoma
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2017-01-24
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase II, multicenter, randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of MOXR0916 in combination with atezolizumab versus placebo and atezolizumab in participants with locally advanced or metastatic urothelial carcinoma (UC) who have not received prior systemic therapy in the locally advanced/metastatic setting and who are ineligible to receive cisplatin-based therapy.

Detailed description: The study design has been amended after the decision to prematurely stop patient accrual due to enrollment challenges. As only 5 participants were enrolled, the study blinding will not be maintained, and placebo infusions will not be administered. Patients assigned to the MOXR0916 arm may continue study treatment with the combination of atezolizumab and MOXR0916 or with atezolizumab alone based on a discussion of benefit and risk with the treating investigator.

Eligibility criteria: Inclusion Criteria:

* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of \<= 2
* Life expectancy \>= 12 weeks
* Histologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma (UC)
* Availability of a representative formalin-fixed paraffin-embedded tumor specimen
* No prior systemic therapy for inoperable locally advanced or metastatic UC
* Ineligible for cisplatin-based chemotherapy as defined by any one of the following criteria: Impaired renal function (glomerular filtration rate \[GFR\] \> 30 but \< 60 milliliter/minute \[mL/min\]); National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0 Grade \>= 2 audiometric hearing loss (of 25 Decibel at two contiguous frequencies or more severe); NCI CTCAE v 4.0 Grade \>= 2 peripheral neuropathy; ECOG Performance Status of 2
* Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1
* Adequate hematologic and end-organ function

Exclusion Criteria:

* Significant cardiovascular disease
* Known clinically significant liver disease
* Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
* Prior treatment with CD137 or OX40 agonists, anti-cytotoxic T-lymphocyte-associated protein (CTLA4), anti-programmed death-1 (PD-1), anti- programmed death-ligand 1 (PD-L1), anti-CD-27, anti- glucocorticoid-induced tumor necrosis factor receptor (GITR) therapeutic antibody or pathway-targeting agents
* Untreated central nervous system (CNS) metastases or active (progressing or requiring corticosteroids for symptomatic control) CNS metastases
* Any history of leptomeningeal disease
* Malignancies other than UC within 5 years prior to Cycle 1, Day 1
* History of autoimmune disease
* History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan
* Active hepatitis B and C virus infection
* Positive HIV test at screening
* Active tuberculosis
* Prior allogeneic stem cell or solid organ transplantation

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 45 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 45 months
Secondary outcomes:
measure: Objective Response (OR) According to RECIST v1.1
timeFrame: Up to approximately 45 months
measure: Duration of Objective Response (DOR) According to RECIST v1.1
timeFrame: Up to approximately 45 months
measure: Time to Pain Progression, Pain Palliation, and Fatigue Progression as Measured by Participant-Reported Severity According to the M. D. Anderson Symptom Inventory (MDASI)
timeFrame: Up to approximately 45 months
measure: Percentage of Participants Reporting Symptom Interference With Daily Living at the Time of Progression According to the MDASI
timeFrame: Up to approximately 45 months
measure: Percentage of Participants With Adverse Event (AEs)
timeFrame: Up to approximately 45 months
measure: Area Under the Plasma Drug Concentration-time Curve (AUC) of MOXR0916 and Atezolizumab
timeFrame: Cycle 1 (each cycle is 21 days), Day 1: predose and 30 min. after atezolizumab infusion; Cycle 1, on Days 8 and 15. Cycles 2 4, Day 1: predose and 30 min. after atezolizumab infusion. Cycles 8, 12, and 16: predose
measure: Maximum Plasma Concentration (Cmax) of MOXR0916 and Atezolizumab
timeFrame: Cycle 1 (each cycle is 21 days), Day 1: predose and 30 min. after atezolizumab infusion; Cycle 1, on Days 8 and 15. Cycles 2 4, Day 1: predose and 30 min. after atezolizumab infusion. Cycles 8, 12, and 16: predose
measure: Minimum Plasma Concentration (Cmin) of MOXR0916 and Atezolizumab
timeFrame: Cycle 1 (each cycle is 21 days), Day 1: predose and 30 min. after atezolizumab infusion; Cycle 1, on Days 8 and 15. Cycles 2 4, Day 1: predose and 30 min. after atezolizumab infusion. Cycles 8, 12, and 16: predose
measure: Clearance of MOXR0916 and Atezolizumab
timeFrame: Cycle 1 (each cycle is 21 days), Day 1: predose and 30 min. after atezolizumab infusion; Cycle 1, on Days 8 and 15. Cycles 2 4, Day 1: predose and 30 min. after atezolizumab infusion. Cycles 8, 12, and 16: predose
measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to MOXR0916 and Atezolizumab
timeFrame: Cycles 1 - 4 and 8, 12, and 16 (each cycle is 21 days), Day 1: predose
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology - HOPE Wilmot
state: Arizona
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Miami
country: United States
facility: Miami Cancer Institute of Baptist Health, Inc.
state: Florida
city: Chicago
country: United States
facility: University of Chicago; Hematology/Oncology
state: Illinois
city: Kansas City
country: United States
facility: Kansas City - Menorah Medical Center
state: Kansas
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Omaha
country: United States
facility: Nebraska Methodist Hospital; Cancer Center
state: Nebraska
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: New York
country: United States
facility: Columbia University Medical Center; Clinical Research Management Office
state: New York
city: Cincinnati
country: United States
facility: Onc/Hem Care Clin Trials LLC
state: Ohio
city: Chattanooga
country: United States
facility: SCRI Tennessee Oncology Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Inst.
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Baylor Sammons Cancer Center
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Lake Wright Cancer Center
state: Virginia
city: Wilrijk
country: Belgium
facility: GasthuisZusters Antwerpen
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - Oncology
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary NHS Trust
city: London
country: United Kingdom
facility: Barts and the London NHS Trust.
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: