Back to resultsA 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
Primary Purpose
Urothelial Carcinoma
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MOXR0916
Atezolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Urothelial Carcinoma
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
Sites / Locations
- Arizona Oncology - HOPE Wilmot
- University of Colorado
- Yale University
- Miami Cancer Institute of Baptist Health, Inc.
- University of Chicago; Hematology/Oncology
- Kansas City - Menorah Medical Center
- Maryland Oncology Hematology, P.A.
- Nebraska Methodist Hospital; Cancer Center
- New York Oncology Hematology, P.C.
- Columbia University Medical Center; Clinical Research Management Office
- Onc/Hem Care Clin Trials LLC
- SCRI Tennessee Oncology Chattanooga
- Sarah Cannon Research Inst.
- Texas Oncology-Baylor Sammons Cancer Center
- Virginia Oncology Associates - Lake Wright Cancer Center
- GasthuisZusters Antwerpen
- Princess Margaret Cancer Center
- Seoul National University Hospital
- Severance Hospital, Yonsei University Health System
- Asan Medical Center - Oncology
- Leicester Royal Infirmary NHS Trust
- Barts and the London NHS Trust.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
MOXR0916 plus Atezolizumab
Atezolizumab
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
Percentage of Participants With Adverse Event (AEs)
An adverse event is any untoward medical occurrence, regardless of causal attribution.
Area Under the Plasma Drug Concentration-time Curve (AUC) of MOXR0916 and Atezolizumab
AUC represents the body's exposure to an administered drug.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03029832
Brief Title
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
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Terminated
Why Stopped
The study was prematurely terminated due to slow patient accrual and discontinuation of clinical development of MOXR0916 due to Sponsor's strategic priorities.
Study Start Date
April 27, 2017 (Actual)
Primary Completion Date
April 25, 2018 (Actual)
Study Completion Date
April 25, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urothelial Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
The study design has been amended in that the study blinding will not be maintained.
Allocation
Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MOXR0916 plus Atezolizumab
Arm Type
Experimental
Arm Title
Atezolizumab
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
MOXR0916
Intervention Description
MOXR0916, 300 milligram (mg) by intravenous (IV) infusion on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Intervention Description
Atezolizumab, 1200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
Up to approximately 45 months
Title
Overall Survival (OS)
Description
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.
Time Frame
Up to approximately 45 months
Secondary Outcome Measure Information:
Title
Objective Response (OR) According to RECIST v1.1
Description
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.
Time Frame
Up to approximately 45 months
Title
Duration of Objective Response (DOR) According to RECIST v1.1
Description
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.
Time Frame
Up to approximately 45 months
Title
Time to Pain Progression, Pain Palliation, and Fatigue Progression as Measured by Participant-Reported Severity According to the M. D. Anderson Symptom Inventory (MDASI)
Description
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.
Time Frame
Up to approximately 45 months
Title
Percentage of Participants Reporting Symptom Interference With Daily Living at the Time of Progression According to the MDASI
Description
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.
Time Frame
Up to approximately 45 months
Title
Percentage of Participants With Adverse Event (AEs)
Description
An adverse event is any untoward medical occurrence, regardless of causal attribution.
Time Frame
Up to approximately 45 months
Title
Area Under the Plasma Drug Concentration-time Curve (AUC) of MOXR0916 and Atezolizumab
Description
AUC represents the body's exposure to an administered drug.
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
Title
Maximum Plasma Concentration (Cmax) of MOXR0916 and Atezolizumab
Description
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.
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
Title
Minimum Plasma Concentration (Cmin) of MOXR0916 and Atezolizumab
Description
Cmin refers to the minimum (trough) serum concentration of a drug in a specified compartment or test area of the body.
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
Title
Clearance of MOXR0916 and Atezolizumab
Description
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
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
Title
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to MOXR0916 and Atezolizumab
Description
ATAs may be produced by the body in response to an administered drug.
Time Frame
Cycles 1 - 4 and 8, 12, and 16 (each cycle is 21 days), Day 1: predose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Oncology - HOPE Wilmot
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85710
Country
United States
Facility Name
University of Colorado
City
Denver
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Miami Cancer Institute of Baptist Health, Inc.
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
University of Chicago; Hematology/Oncology
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Kansas City - Menorah Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66209
Country
United States
Facility Name
Maryland Oncology Hematology, P.A.
City
Columbia
State/Province
Maryland
ZIP/Postal Code
21044
Country
United States
Facility Name
Nebraska Methodist Hospital; Cancer Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
New York Oncology Hematology, P.C.
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Columbia University Medical Center; Clinical Research Management Office
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Onc/Hem Care Clin Trials LLC
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
SCRI Tennessee Oncology Chattanooga
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Sarah Cannon Research Inst.
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Texas Oncology-Baylor Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Virginia Oncology Associates - Lake Wright Cancer Center
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
GasthuisZusters Antwerpen
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Princess Margaret Cancer Center
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1Z5
Country
Canada
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center - Oncology
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Leicester Royal Infirmary NHS Trust
City
Leicester
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Facility Name
Barts and the London NHS Trust.
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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
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