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Clinical Trial 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.


Clinical Trial 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. ;


Study Design


Related Conditions & MeSH terms

  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Transitional Cell
  • Clinical Stage III Cutaneous Melanoma AJCC v8
  • Clinical Stage IV Cutaneous Melanoma AJCC v8
  • Kidney Neoplasms
  • Locally Advanced Bladder Urothelial Carcinoma
  • Locally Advanced Lung Non-Small Cell Carcinoma
  • Locally Advanced Renal Pelvis Urothelial Carcinoma
  • Locally Advanced Ureter Urothelial Carcinoma
  • Locally Advanced Urethral Urothelial Carcinoma
  • Lung Neoplasms
  • Malignant Solid Neoplasm
  • Melanoma
  • Metastatic Bladder Carcinoma
  • Metastatic Bladder Urothelial Carcinoma
  • Metastatic Lung Non-Small Cell Carcinoma
  • Metastatic Melanoma
  • Metastatic Renal Pelvis Urothelial Carcinoma
  • Metastatic Ureter Urothelial Carcinoma
  • Metastatic Urethral Carcinoma
  • Metastatic Urethral Urothelial Carcinoma
  • Pathologic Stage III Cutaneous Melanoma AJCC v8
  • Pathologic Stage IIIA Cutaneous Melanoma AJCC v8
  • Pathologic Stage IIIB Cutaneous Melanoma AJCC v8
  • Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
  • Pathologic Stage IIID Cutaneous Melanoma AJCC v8
  • Pathologic Stage IV Cutaneous Melanoma AJCC v8
  • Pelvic Neoplasms
  • Skin Neoplasms
  • Stage III Bladder Cancer AJCC v8
  • Stage III Lung Cancer AJCC v8
  • Stage III Renal Pelvis Cancer AJCC v8
  • Stage III Ureter Cancer AJCC v8
  • Stage III Urethral Cancer AJCC v8
  • Stage IIIA Bladder Cancer AJCC v8
  • Stage IIIA Lung Cancer AJCC v8
  • Stage IIIB Bladder Cancer AJCC v8
  • Stage IIIB Lung Cancer AJCC v8
  • Stage IIIC Lung Cancer AJCC v8
  • Stage IV Bladder Cancer AJCC v8
  • Stage IV Renal Pelvis Cancer AJCC v8
  • Stage IV Ureter Cancer AJCC v8
  • Stage IV Urethral Cancer AJCC v8
  • Stage IVA Lung Cancer AJCC v8
  • Stage IVB Lung Cancer AJCC v8
  • Unresectable Melanoma
  • Ureteral Neoplasms
  • Urethral Neoplasms
  • Urinary Bladder Neoplasms

NCT number NCT04940299
Study type Interventional
Source M.D. Anderson Cancer Center
Contact
Status Active, not recruiting
Phase Phase 2
Start date September 23, 2021
Completion date December 31, 2024

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