Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma
- Conditions
- Locally Advanced Bladder Urothelial CarcinomaLocally Advanced Ureter Urothelial CarcinomaMetastatic Bladder Urothelial CarcinomaMetastatic MelanomaMetastatic Renal Pelvis Urothelial CarcinomaMetastatic Ureter Urothelial CarcinomaPathologic Stage IIID Cutaneous Melanoma AJCC v8Stage III Urethral Cancer AJCC v8Locally Advanced Bladder CarcinomaLocally Advanced Renal Pelvis Urothelial Carcinoma
- Interventions
- Registration Number
- NCT04940299
- Lead Sponsor
- M.D. Anderson Cancer Center
- Brief Summary
This phase II trial investigates the side effects of tocilizumab, ipilimumab, and nivolumab in treating patients with melanoma, non-small cell lung cancer, or urothelial carcinoma that has spread to nearby tissue or lymph nodes (locally advanced). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Tocilizumab is a monoclonal antibody that may interfere with the immune system to decrease immune-related toxicities. Giving tocilizumab, ipilimumab, and nivolumab may kill more tumor cells.
- Detailed Description
PRIMARY OBJECTIVES:
I. To characterize the safety and tolerability of systemic tocilizumab, an IL-6 receptor antagonist, in combination with Ipilimumab and nivolumab as front-line treatment for patients with advanced cutaneous melanoma, urothelial carcinoma and in EGFR mutant non-small cell lung cancer (NSCLC).
II. To determine the grade 3 or higher toxicity rate of Tocilizumab in combination with Ipilimumab and nivolumab for patients with advanced cutaneous melanoma.
SECONDARY OBJECTIVES:
I. To estimate the objective response rate (ORR), defined as the proportion of patients with complete response (CR) or partial response (PR), and durable response rate (DRR), defined as the proportion of patients with objective responses of \> 6 months duration, as determined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and immune related RECIST (irRECIST).
II. To estimate progression-free survival (PFS) defined as the time from the start of treatment to disease progression or death, whichever occurs first.
III. To estimate overall survival (OS) defined as the time from the start of treatment to death from any cause.
EXPLORATORY OBJECTIVE:
I. To assess pre- and post-treatment blood/tumor biopsies for immunologic assessment and to explore any potential association between biomarker measurements and antitumor activity.
OUTLINE: OUTLINE: Patients are assigned to 1 of 3 cohorts: 1=melanoma, 2=Urothelial, 3=NSCLC.
COHORT 1: Patients with melanoma will receive ipilimumab intravenously (IV) over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Cohort 1 will be divided into 2 sub-groups: sub-group 1 of 25 patients, and subgroup 2 of 10 patients that will consist of varying Tocilizumab administration doses. For sub-group 1, Tocilizumab 162mg will be administered subcutaneously every 2 weeks starting week 0, up to 12 weeks for a total of 6 doses. For sub-group 2 , Tocilizumab 162mg will be administered subcutaneously once every week starting at week 0 up to week 6 followed by Tocilizumab administered subcutaneously every 2 weeks starting at week 6 up to 12 weeks for a total of 9 doses.
COHORT 2: Patients with urothelial cancer will receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Starting on week 1, patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses) in the absence of disease progression or unacceptable toxicity.
COHORT 3: Patients with NSCLC receive ipilimumab IV over 90 minutes every 6 weeks and nivolumab IV over 30 minutes every 2 weeks for up to 2 years. Patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses). Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 2 years.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 35
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 (ipilimumab, nivolumab, tocilizumab) Ipilimumab Patients with melanoma will receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Cohort 1 will be divided into 2 sub-groups: sub-group 1 of 25 patients, and subgroup 2 of 10 patients that will consist of varying Tocilizumab administration doses. For sub-group 1, Tocilizumab 162mg will be administered subcutaneously every 2 weeks starting week 0, up to 12 weeks for a total of 6 doses. For sub-group 2 , Tocilizumab 162mg will be administered subcutaneously once every week starting at week 0 up to week 6 followed by Tocilizumab administered subcutaneously every 2 weeks starting at week 6 up to 12 weeks for a total of 9 doses. Cohort 2 (ipilimumab, nivolumab, tocilizumab) Ipilimumab Patients with urothelial cancer will receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Starting on week 1, patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses) in the absence of disease progression or unacceptable toxicity. Cohort 3 (ipilimumab,, nivolumab, tocilizumab) Nivolumab Patients with NSCLC receive ipilimumab IV over 90 minutes every 6 weeks and nivolumab IV over 30 minutes every 2 weeks for up to 2 years. Patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses). Treatment continues in the absence of disease progression or unacceptable toxicity. Cohort 1 (ipilimumab, nivolumab, tocilizumab) Nivolumab Patients with melanoma will receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Cohort 1 will be divided into 2 sub-groups: sub-group 1 of 25 patients, and subgroup 2 of 10 patients that will consist of varying Tocilizumab administration doses. For sub-group 1, Tocilizumab 162mg will be administered subcutaneously every 2 weeks starting week 0, up to 12 weeks for a total of 6 doses. For sub-group 2 , Tocilizumab 162mg will be administered subcutaneously once every week starting at week 0 up to week 6 followed by Tocilizumab administered subcutaneously every 2 weeks starting at week 6 up to 12 weeks for a total of 9 doses. Cohort 1 (ipilimumab, nivolumab, tocilizumab) Tocilizumab Patients with melanoma will receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Cohort 1 will be divided into 2 sub-groups: sub-group 1 of 25 patients, and subgroup 2 of 10 patients that will consist of varying Tocilizumab administration doses. For sub-group 1, Tocilizumab 162mg will be administered subcutaneously every 2 weeks starting week 0, up to 12 weeks for a total of 6 doses. For sub-group 2 , Tocilizumab 162mg will be administered subcutaneously once every week starting at week 0 up to week 6 followed by Tocilizumab administered subcutaneously every 2 weeks starting at week 6 up to 12 weeks for a total of 9 doses. Cohort 2 (ipilimumab, nivolumab, tocilizumab) Nivolumab Patients with urothelial cancer will receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Starting on week 1, patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses) in the absence of disease progression or unacceptable toxicity. Cohort 2 (ipilimumab, nivolumab, tocilizumab) Tocilizumab Patients with urothelial cancer will receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment with ipilimumab and nivolumab repeats every 3 weeks for 4 doses, then treatment with nivolumab repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Starting on week 1, patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses) in the absence of disease progression or unacceptable toxicity. Cohort 3 (ipilimumab,, nivolumab, tocilizumab) Ipilimumab Patients with NSCLC receive ipilimumab IV over 90 minutes every 6 weeks and nivolumab IV over 30 minutes every 2 weeks for up to 2 years. Patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses). Treatment continues in the absence of disease progression or unacceptable toxicity. Cohort 3 (ipilimumab,, nivolumab, tocilizumab) Tocilizumab Patients with NSCLC receive ipilimumab IV over 90 minutes every 6 weeks and nivolumab IV over 30 minutes every 2 weeks for up to 2 years. Patients also receive tocilizumab SC every 2 weeks for up to 12 weeks (6 doses). Treatment continues in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Incidence of dose limiting toxicity Up to 2 years Will be summarized overall and for each tumor type using frequencies and percentages.
Occurrence of one or more grade 3 or higher adverse event in a given patient (Cohort 1) Up to 2 years Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. Grade 3 or greater toxicity rate will be computed along with their associated exact 95% confidence interval.
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) Time from the start of treatment to disease progression (defined by irRECIST) or death, whichever occurs first, assessed up to 2 years Will be estimated using the Kaplan-Meier method. Median PFS along with its corresponding 95% confidence intervals will be presented as well as rates at specific timepoints.
Best overall response Up to 2 years Will be defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and immune related Response Evaluation Criteria in Solid Tumors (irRECIST). Will be computed along with their associated 95% credible interval and exact 95% confidence interval.
Overall survival (OS) Time from the start of treatment to death from any cause, assessed up to 2 years Will be estimated using the Kaplan-Meier method. Median OS along with its corresponding 95% confidence intervals will be presented as well as rates at specific timepoints.
Trial Locations
- Locations (1)
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States