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

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

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.

Study Overview

• Status: Terminated
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Drug: MOXR0916; Drug: Atezolizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Wilrijk, Belgium, 2610
    • GasthuisZusters Antwerpen
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Center
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center - Oncology
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary NHS Trust
  • London, United Kingdom, EC1A 7BE
    • Barts and the London NHS Trust.
• United States
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Arizona Oncology - HOPE Wilmot
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute of Baptist Health, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago; Hematology/Oncology
  • Kansas
    • Kansas City, Kansas, United States, 66209
      • Kansas City - Menorah Medical Center
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology, P.A.
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital; Cancer Center
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology, P.C.
    • New York, New York, United States, 10032
      • Columbia University Medical Center; Clinical Research Management Office
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Onc/Hem Care Clin Trials LLC
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Scri Tennessee Oncology Chattanooga
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Inst.
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor Sammons Cancer Center
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates - Lake Wright Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MOXR0916 plus Atezolizumab	Drug: MOXR0916; MOXR0916, 300 milligram (mg) by intravenous (IV) infusion on Day 1 of each 21-day cycle.; Drug: Atezolizumab; Atezolizumab, 1200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle.
ACTIVE_COMPARATOR: Atezolizumab	Drug: Atezolizumab; Atezolizumab, 1200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline); and an absolute increase of >= 5 millimeter (mm) in the sum of diameters.	Up to approximately 45 months
Overall Survival (OS)	Kaplan Meier estimate of median OS was defined as the time at which half of the participants had died, regardless of the cause of death.	Up to approximately 45 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response (OR) According to RECIST v1.1	OR is defined as a complete response (CR) or partial response (PR) on two consecutive occasions >= 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.	Up to approximately 45 months
Duration of Objective Response (DOR) According to RECIST v1.1	DOR is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1. Objective response is defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.	Up to approximately 45 months
Time to Pain Progression, Pain Palliation, and Fatigue Progression as Measured by Participant-Reported Severity According to the M. D. Anderson Symptom Inventory (MDASI)	The MDASI is a cancer-related, self-reported questionnaire consisting of 19 items assessing symptom severity and interference with different aspects of a participant's life. The MDASI items are rated from 0 to 10, with 0 indicating that the symptom is either not present or does not interfere with the participant's activities and 10 indicating that the symptom is "as bad as you can imagine" or "interfered completely" with the participant's life.	Up to approximately 45 months
Percentage of Participants Reporting Symptom Interference With Daily Living at the Time of Progression According to the MDASI	The MDASI is a cancer-related, self-reported questionnaire consisting of 19 items assessing symptom severity and interference with different aspects of a participant's life. The MDASI items are rated from 0 to 10, with 0 indicating that the symptom is either not present or does not interfere with the participant's activities and 10 indicating that the symptom is "as bad as you can imagine" or "interfered completely" with the participant's life.	Up to approximately 45 months
Percentage of Participants With Adverse Event (AEs)	An adverse event is any untoward medical occurrence, regardless of causal attribution.	Up to approximately 45 months
Area Under the Plasma Drug Concentration-time Curve (AUC) of MOXR0916 and Atezolizumab	AUC represents the body's exposure to an administered drug.	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
Maximum Plasma Concentration (Cmax) of MOXR0916 and Atezolizumab	Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose.	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
Minimum Plasma Concentration (Cmin) of MOXR0916 and Atezolizumab	Cmin refers to the minimum (trough) serum concentration of a drug in a specified compartment or test area of the body.	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
Clearance of MOXR0916 and Atezolizumab	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.	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
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to MOXR0916 and Atezolizumab	ATAs may be produced by the body in response to an administered drug.	Cycles 1 - 4 and 8, 12, and 16 (each cycle is 21 days), Day 1: predose

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 27, 2017
• Primary Completion (ACTUAL): April 25, 2018
• Study Completion (ACTUAL): April 25, 2018

Study Registration Dates

• First Submitted: January 18, 2017
• First Submitted That Met QC Criteria: January 20, 2017
• First Posted (ESTIMATE): January 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 31, 2019
• Last Update Submitted That Met QC Criteria: May 30, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Antineoplastic Agents; Atezolizumab
• Other Study ID Numbers: GO39590; 2016-004165-58 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No