Urothelial CarcinomaPhase 2NCT03029832
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 2 study testing MOXR0916 and Atezolizumab in people with Urothelial Carcinoma, run by Genentech, Inc. at 22 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma
- What is being tested?
- MOXR0916 and Atezolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 22 sitesin 5 countries
- Study dates
- 27 Apr 2017to 25 Apr 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
22 sites in 5 countries.
22 sites in 5 countries
United States15 sites
New York Oncology Hematology, P.C.
Albany, New York, 12208
SCRI Tennessee Oncology Chattanooga
Chattanooga, Tennessee, 37404
University of Chicago; Hematology/Oncology
Chicago, Illinois, 60637
Onc/Hem Care Clin Trials LLC
Cincinnati, Ohio, 45242
Maryland Oncology Hematology, P.A.
Columbia, Maryland, 21044
Texas Oncology-Baylor Sammons Cancer Center
Dallas, Texas, 75246
University of Colorado
Denver, Colorado, 80045
Kansas City - Menorah Medical Center
Kansas City, Kansas, 66209
Miami Cancer Institute of Baptist Health, Inc.
Miami, Florida, 33176
Sarah Cannon Research Inst.
Nashville, Tennessee, 37203
Yale University
New Haven, Connecticut, 06510
Columbia University Medical Center; Clinical Research Management Office
New York, New York, 10032
Virginia Oncology Associates - Lake Wright Cancer Center
Norfolk, Virginia, 23502
Nebraska Methodist Hospital; Cancer Center
Omaha, Nebraska, 68114
Arizona Oncology - HOPE Wilmot
Tucson, Arizona, 85710
South Korea3 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center - Oncology
Seoul, 05505
United Kingdom2 sites
Leicester Royal Infirmary NHS Trust
Leicester, LE1 5WW
Barts and the London NHS Trust.
London, EC1A 7BE
About this study
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
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.
Read the 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.
- Conditions
- Urothelial Carcinoma
- Being tested
- MOXR0916, Atezolizumab
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MOXR0916Drug
MOXR0916, 300 milligram (mg) by intravenous (IV) infusion on Day 1 of each 21-day cycle.
AtezolizumabDrug
Atezolizumab, 1200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| MOXR0916 plus Atezolizumab | Experimental | Not described Receives: Drug: MOXR0916; Drug: Atezolizumab |
| Atezolizumab | Active comparator | Not described Receives: Drug: Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to approximately 45 months
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 45 months
Percentage of Participants With Adverse Event (AEs)
An adverse event is any untoward medical occurrence, regardless of causal attribution.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Cycles 1 - 4 and 8, 12, and 16 (each cycle is 21 days), Day 1: predose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2017 (estimated)
- Study start27 Apr 2017
- Primary completion25 Apr 2018
- Study completion25 Apr 2018
Why it stopped: The study was prematurely terminated due to slow patient accrual and discontinuation of clinical development of MOXR0916 due to Sponsor's strategic priorities.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03029832
- Sponsor's protocol ID
- GO39590
- Other IDs
- 2016-004165-58, 2016
- Status last verified
- May 2019
- First submitted
- 18 Jan 2017
- Last updated
- 31 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03029832
- Acronym / sponsor ID
- GO39590
- Conditions
- Urothelial Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was prematurely terminated due to slow patient accrual and discontinuation of clinical development of MOXR0916 due to Sponsor's strategic priorities.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Apr 2017 (actual)
- Primary completion
- 25 Apr 2018 (actual)
- Study completion
- 25 Apr 2018 (actual)
- First posted
- 24 Jan 2017 (estimated)
- Results
- Posted 31 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MOXR0916 plus Atezolizumab | Experimental | Drug: MOXR0916, Drug: Atezolizumab |
| Atezolizumab | Active comparator | Drug: Atezolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MOXR0916MOXR0916, 300 milligram (mg) by intravenous (IV) infusion on Day 1 of each 21-day cycle. | Drug | MOXR0916 plus Atezolizumab |
| AtezolizumabAtezolizumab, 1200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle. | Drug | Atezolizumab, MOXR0916 plus Atezolizumab |
Primary outcome
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.
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.
10 secondary outcomes
Objective Response (OR) According to RECIST v1.1
Time frame: Up to approximately 45 months
Duration of Objective Response (DOR) According to RECIST v1.1
Time frame: 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
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
Percentage of Participants With Adverse Event (AEs)
Time frame: 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
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
22 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MOXR0916 and Atezolizumab in people with Urothelial Carcinoma, run by Genentech, Inc. at 22 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, South Korea, United Kingdom, Belgium, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) (time frame: Up to approximately 45 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2019.