Phase II Randomized Trial of Immunotherapy Versus Immunotherapy and Radiation Therapy for Platinum Ineligible/Refractory Metastatic Urothelial Cancer (IMMORTAL)
Overview
- Phase
- Phase 2
- Intervention
- Biospecimen Collection
- Conditions
- Metastatic Urothelial Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 1
- Locations
- 83
- Primary Endpoint
- Tumor Response
- Status
- Terminated
- Last Updated
- 8 months ago
Overview
Brief Summary
This phase II trial compares the effect of adding radiation therapy to an immunotherapy drug called pembrolizumab versus pembrolizumab alone in treating patients with urothelial cancer that has spread from where it first started (primary site) to other places in the body (metastatic). The addition of radiation to immunotherapy may shrink the cancer, but it could also cause side effects. Immunotherapy with monoclonal antibodies such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy (SBRT) is a type of radiation therapy that uses high energy x-rays to kill tumor cells and shrink tumors. This method uses special equipment to position a patient and precisely deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and may cause less damage to normal tissue than conventional radiation therapy. The combination of pembrolizumab and radiation therapy may be more efficient in killing tumor cells.
Detailed Description
PRIMARY OBJECTIVE: I. To compare the overall response rates by 6 months in patients with advanced urothelial carcinoma when treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. SECONDARY OBJECTIVES: I. To compare the response rates using immune related Response Evaluation Criteria in Solid Tumors (iRECIST) as assessed by central review. II. To compare progression-free survival (PFS) and overall survival (OS) for patients treated with immunotherapy and immunotherapy plus radiotherapy. III. To compare the rates of treatment discontinuation at 1 year. IV. To assess adverse events experienced by patients treated with immunotherapy and immunotherapy plus radiotherapy via the Common Terminology Criteria for Adverse Events (CTCAE) and Patient Reported Outcome (PRO)-CTCAE. IV. To determine whether treatment effects are similar for key subgroups including those defined by the stratification variables. QUALITY OF LIFE CORRELATIVE STUDY OBJECTIVES: I. To compare patient-reported fatigue as assessed by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue 8a from baseline through 24 months between patients treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. II. To compare health-related quality of life (HRQOL) as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core (C)30 from baseline through 24 months between patients treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. III. To compare urinary symptoms as assessed by the EORTC QLQ-BLM30 from baseline through 24 months between patients treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. IV. To compare patient-reported diarrhea, shortness of breath and pain as assessed by the EORTC QLQ-C30 from baseline through 24 months between patients treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. V. To compare health utilities and quality-adjusted survival between patients treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. VI. To compare other scale scores of the EORTC QLQ-C30 (global health status and quality of life; physical, role, emotional, cognitive, and social function; symptoms) and EORTC QLQ-BLM30 (urostomy problems, catheter problems, future perspectives, abdominal bloating and flatulence, body image, sexual function) at 45 days, and at 6, 12, and 24 months between patients treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive pembrolizumab intravenously (IV) over 25-40 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), bone scan and/or positron emission tomography (PET) scan, as well as optional urine and blood sample collection throughout the study. ARM B: Patients receive pembrolizumab as in Arm A. Patients also undergo SBRT once daily (QD) every other day for 3 fractions over 2 weeks that must be completed before 12 weeks after the first dose of pembrolizumab in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan, and/or PET scan, as well as optional urine and blood sample collection throughout the study. After completion of study treatment, patients are followed up within 12 weeks and then every 3 months for 3 years following registration.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed metastatic urothelial carcinoma
- •Patients must be either ineligible for platinum treatment or platinum refractory as defined below:
- •Platinum-ineligible: If patients meet any one of the following criteria:
- •Impaired renal function (creatinine clearance \[CrCl\] of \< 30 mL/min)
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of \> 2
- •Grade \> 2 peripheral neuropathy
- •New York Heart Association (NYHA) Heart Failure of \> 3
- •Platinum-refractory: If patients meet any one of the following criteria:
- •Prior platinum-based perioperative chemotherapy within 12 months of relapse
- •Prior platinum-based chemotherapy for metastatic disease
Exclusion Criteria
- Not provided
Arms & Interventions
Arm A (pembrolizumab)
Patients receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Biospecimen Collection
Arm A (pembrolizumab)
Patients receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Bone Scan
Arm A (pembrolizumab)
Patients receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Computed Tomography
Arm A (pembrolizumab)
Patients receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Magnetic Resonance Imaging
Arm A (pembrolizumab)
Patients receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Pembrolizumab
Arm A (pembrolizumab)
Patients receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Positron Emission Tomography
Arm A (pembrolizumab)
Patients receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Questionnaire Administration
Arm B (pembrolizumab, SBRT)
Patients receive pembrolizumab as in Arm A. Patients also undergo SBRT QD every other day for 3 fractions over 2 weeks that must be completed before 12 weeks after the first dose of pembrolizumab in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan, and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Biospecimen Collection
Arm B (pembrolizumab, SBRT)
Patients receive pembrolizumab as in Arm A. Patients also undergo SBRT QD every other day for 3 fractions over 2 weeks that must be completed before 12 weeks after the first dose of pembrolizumab in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan, and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Bone Scan
Arm B (pembrolizumab, SBRT)
Patients receive pembrolizumab as in Arm A. Patients also undergo SBRT QD every other day for 3 fractions over 2 weeks that must be completed before 12 weeks after the first dose of pembrolizumab in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan, and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Computed Tomography
Arm B (pembrolizumab, SBRT)
Patients receive pembrolizumab as in Arm A. Patients also undergo SBRT QD every other day for 3 fractions over 2 weeks that must be completed before 12 weeks after the first dose of pembrolizumab in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan, and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Magnetic Resonance Imaging
Arm B (pembrolizumab, SBRT)
Patients receive pembrolizumab as in Arm A. Patients also undergo SBRT QD every other day for 3 fractions over 2 weeks that must be completed before 12 weeks after the first dose of pembrolizumab in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan, and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Pembrolizumab
Arm B (pembrolizumab, SBRT)
Patients receive pembrolizumab as in Arm A. Patients also undergo SBRT QD every other day for 3 fractions over 2 weeks that must be completed before 12 weeks after the first dose of pembrolizumab in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan, and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Positron Emission Tomography
Arm B (pembrolizumab, SBRT)
Patients receive pembrolizumab as in Arm A. Patients also undergo SBRT QD every other day for 3 fractions over 2 weeks that must be completed before 12 weeks after the first dose of pembrolizumab in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan, and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Questionnaire Administration
Arm B (pembrolizumab, SBRT)
Patients receive pembrolizumab as in Arm A. Patients also undergo SBRT QD every other day for 3 fractions over 2 weeks that must be completed before 12 weeks after the first dose of pembrolizumab in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan, and/or PET scan, as well as optional urine and blood sample collection throughout the study.
Intervention: Stereotactic Body Radiation Therapy
Outcomes
Primary Outcomes
Tumor Response
Time Frame: Up to 6 months from randomization
Will be defined as a complete response (CR) or partial response (PR) as assessed by the treating physician using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
Secondary Outcomes
- Tumor Response(Up to 3 years from randomization)
- Progression-free Survival(Time from randomization until disease progression as assessed by the treating physician using RECIST 1.1 or death due to any cause, assessed up to 3 years)
- Overall Survival(Time from randomization until death due to any cause. Patients who are not known to be dead at time of analysis will be censored at the time of their last follow-up, assessed up to 3 years)
- Rate of Treatment Discontinuation(At 1 year)
- Incidence of Adverse Events(Up to 3 years from randomization)