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

May 30, 2019 updated by: Genentech, Inc.

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
5

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: Up to approximately 45 months
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)
Time Frame: Up to approximately 45 months
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objective Response (OR) According to RECIST v1.1
Time Frame: Up to approximately 45 months
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
Time Frame: Up to approximately 45 months
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)
Time Frame: Up to approximately 45 months
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
Time Frame: Up to approximately 45 months
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)
Time Frame: Up to approximately 45 months
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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 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
Time Frame: Cycles 1 - 4 and 8, 12, and 16 (each cycle is 21 days), Day 1: predose
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Genentech, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 27, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 25, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 25, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 18, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2017

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 24, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 31, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 30, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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