Clinical Trial 18786

Cancer Type: Cutaneous
Interventions:BMS-936558 (Nivolumab); Ipilimumab; Nivolumab; Yervoy (Ipilimumab)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Sungjune Kim

Overview

Study Title

A Phase 2, Randomized, Multi-institutional Study of Nivolumab and Ipilimumab versus Nivolumab, Ipilimumab and Stereotactic Body Radiation Therapy for Metastatic Merkel Cell Carcinoma

Summary

The purpose of this study is to test the effectiveness, safety, and tolerability of the drugs nivolumab plus ipilimumab with or without the addition of stereotactic body radiation therapy (SBRT). Nivolumab is an antibody (a type of human protein) that is being tested to see if it will stimulate the body's immune system to work against tumor cells. This study will test an investigational use of nivolumab.

Objective

Primary: To compare the efficacy, as measured by objective response rate (ORR), provided by nivolumab plus ipilimumab with or without SBRT in subjects with metastatic Merkel cell carcinoma. Secondary: To compare the progression free survival (PFS) of nivolumab and ipilimumab versus SBRT plus nivolumab and ipilimumab in subjects with metastatic Merkel cell carcinoma. To compare the overall survival (OS) of nivolumab and ipilimumab versus SBRT plus nivolumab and ipilimumab in subjects with metastatic Merkel cell carcinoma. To evaluate the local control of irradiated tumor provided by SBRT in combination with nivolumab and ipilimumab. To assess the overall safety and tolerability of of nivolumab and ipilimumab versus SBRT plus nivolumab and ipilimumab in subjects with metastatic Merkel cell carcinoma. To evaluate whether PD-L1 expression is a predictive biomarker for ORR. To evaluate the Health Related Quality of Life (HRQoL) as assessed by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30.

Inclusion Criteria

  • At least 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) Performance Status less than 2
  • Active disease measurable by CT or MRI
  • Prior chemotherapy or immunotherapy will be allowed if new or persistent measurable site(s) of disease are present.
  • Prior radiation therapy will be allowed if active measurable disease was not previously treated with radiation therapy.
  • Must be either recurrent or Stage IV American Joint Committee on Cancer (AJCC) (7th edition) and have histologically confirmed Merkel cell carcinoma with at least 2 distinct lesions in order to be eligible.
  • Must have at least 2 distinct lesions as documented by a complete physical examination and imaging studies within 4 weeks prior to randomization. Imaging studies must include a diagnostic CT scan of the involved disease sites and all known sites of resected disease and brain magnetic resonance (MRI) or CT (brain CT allowable if MRI is contraindicated or if there is no known history of resected brain lesions).
  • Tumor tissue from the core biopsy or resected site of disease must be provided for biomarker analyses.

  • Exclusion Criteria

  • History of Grade 3 toxicity or use of infliximab with prior immunotherapy
  • Patients with brain metastasis.
  • Active, known, or suspected autoimmune disease. Potential participants with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll.
  • Patients with previous non-Merkel cell carcinoma malignancies are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required during the study period (exceptions include but are not limited to, non-melanoma/Merkel cell carcinoma skin cancers; in situ bladder cancer, in situ gastric cancer, in situ colon cancers; in situ cervical cancers/dysplasia; or breast carcinoma in situ).
  • A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.