Study of Nivolumab in Combination With Ipilimumab or Standard of Care Chemotherapy Compared to the Standard of Care Chemotherapy Alone in Treatment of Participants With Untreated Inoperable or Metastatic Urothelial Cancer
- Conditions
- Urothelial Cancer
- Interventions
- Registration Number
- NCT03036098
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to determine whether an investigational immunotherapy nivolumab in combination with ipilimumab or in combination with standard of care chemotherapy is more effective than standard of care chemotherapy alone in treating participants with previously untreated inoperable or metastatic urothelial cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1314
- Histological or cytological evidence of metastatic or surgically inoperable transitional cell cancer (TCC) of the urothelium involving the renal pelvis, ureter, bladder or urethra
- No prior systemic chemotherapy for metastatic or surgically inoperable urothelial cancer (UC)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Women and men must agree to follow specific methods of contraception, if applicable
- Disease that is suitable for local therapy administered with curative intent
- Any serious or uncontrolled medical disorder in the opinion of the investigator that may increase the risk associated with study participation or study drug administration or interfere with the interpretation of study results
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
Other protocol-defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm D: Standard of care chemotherapy Gemcitabine - Arm C: Investigational immunotherapy Cisplatin - Arm A: Investigational immunotherapy Nivolumab - Arm C: Investigational immunotherapy Nivolumab - Arm A: Investigational immunotherapy Ipilimumab - Arm B: Standard of care chemotherapy Carboplatin - Arm B: Standard of care chemotherapy Gemcitabine - Arm B: Standard of care chemotherapy Cisplatin - Arm C: Investigational immunotherapy Gemcitabine - Arm D: Standard of care chemotherapy Cisplatin -
- Primary Outcome Measures
Name Time Method Overall Survival (OS) in Cisplatin-ineligible Randomized Participants for Primary Study From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months) This measure looks at how long participants who cannot receive cisplatin (a type of chemotherapy) live after being placed into a treatment group in the primary study.
Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization.
This helps to understand if the treatment can help people who are unable to receive cisplatin chemotherapy live longer.Overall Survival (OS) in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Randomized Participants by Immunohistochemistry (IHC) for Primary Study From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months) This measure looks at how long participants with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a laboratory test called immunohistochemistry or IHC) live after being placed into a treatment group in the primary study.
Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization.
This helps to understand whether the treatment can help people with PD-L1 positive tumors live longer.Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Cisplatin-eligible Participants for Sub-study From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months) This measure looks at how long people who can receive cisplatin chemotherapy live without their cancer getting worse after being assigned to a treatment group in the sub-study. Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. This helps to understand if the treatment helps people eligible for cisplatin live longer without their cancer progressing.
Overall Survival (OS) in Cisplatin-eligible Participants for Sub-study From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months) This measure looks at how long people who are able to receive cisplatin (a type of chemotherapy) live after being placed into a treatment group in the sub-study.
Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization.
This helps to understand if the treatment can help people who are eligible for cisplatin chemotherapy live longer.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) in All Randomized Participants for Primary Study From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months) This measure looks at how long all participants live after being placed into a treatment group in the primary study.
Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization.
This helps to understand whether the treatment can help all participants in the study live longer.Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Cisplatin-ineligible Randomized Participants for Primary Study From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months) This measure looks at how long people who cannot receive cisplatin chemotherapy live without their cancer getting worse after being assigned to a treatment group in the primary study. Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. This helps to understand if the treatment helps people unable to receive cisplatin live longer without their cancer progressing.
Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Participants for Primary Study From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months) This measure looks at how long people with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a lab test) live without their cancer getting worse after being assigned to a treatment group in the primary study. Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. This helps to understand if the treatment helps people with PD-L1 positive tumors live longer without their cancer progressing.
Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in All Randomized Participants for Primary Study From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months) This measure looks at how long all participants in the primary study live without their cancer getting worse after being assigned to a treatment group.
Progression-Free Survival (PFS) is defined as the time from when a participant is assigned to a treatment group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment the participant received. These experts use standard rules (called RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check.
This helps to understand whether the treatment can help participants live longer without their cancer progressing.Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study At Baseline, Week 4, Week 10, Week 16, Week 20, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 108, Week 120, Week 144, Week 156, Week 168, Week 180 and Week 192 The EORTC QLQ-C30 is a questionnaire used to assess the quality of life in cancer patients. It includes a global health status score, which is measured on a 4-point Likert scale: 1 = not at all, 2 = a little, 3 = quite a bit, and 4 = very much. Responses are combined and converted to scores ranging from 0 to 100. A high score for global health status or health-related quality of life (HRQoL) indicates a high overall HRQoL.
Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study At Baseline, Week 4, Week 10, Week 16, Week 20, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 108, and Week 120 The EORTC QLQ-C30 is a questionnaire used to assess the quality of life in cancer patients. It includes a global health status score, which is measured on a 4-point Likert scale: 1 = not at all, 2 = a little, 3 = quite a bit, and 4 = very much. Responses are combined and converted to scores ranging from 0 to 100. A high score for global health status or health-related quality of life (HRQoL) indicates a high overall HRQoL.
Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] by Programmed Death-Ligand 1 (PD-L1) Expression at ≥1% Expression by Immunohistochemistry (IHC) for Sub-study From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months) This measure looks at how long participants with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a lab test called immunohistochemistry or IHC) live without their cancer getting worse after being assigned to a treatment group in the sub-study.
Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check.Overall Survival (OS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] by Programmed Death-Ligand 1 (PD-L1) Expression at ≥1% Expression by Immunohistochemistry (IHC) for Sub-study From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months) This measure looks at how long participants with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a laboratory test called immunohistochemistry or IHC) live after being placed into a treatment group in the sub-study.
Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization.
This helps to understand whether the treatment can help people with PD-L1 positive tumors live longer. The results are reviewed by independent experts who do not know which treatment each participant received, using standard criteria for measuring tumor response.
Trial Locations
- Locations (174)
Local Institution - 0001
🇺🇸Anchorage, Alaska, United States
Local Institution - 0115
🇺🇸Fresno, California, United States
St Joseph Heritage Healthcare
🇺🇸Santa Rosa, California, United States
Local Institution - 0051
🇺🇸Boca Raton, Florida, United States
Local Institution - 0087
🇺🇸Fort Lauderdale, Florida, United States
Local Institution - 0062
🇺🇸Jacksonville, Florida, United States
Local Institution - 0004
🇺🇸Athens, Georgia, United States
Local Institution - 0033
🇺🇸Thomasville, Georgia, United States
Local Institution - 0046
🇺🇸Chicago, Illinois, United States
Local Institution - 0117
🇺🇸New Orleans, Louisiana, United States
Scroll for more (164 remaining)Local Institution - 0001🇺🇸Anchorage, Alaska, United States