Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Sarcoma That Cannot Be Removed by Surgery

Metastatic Soft Tissue Sarcoma Clinical Trial

Official title: Randomized Phase II Study of Nivolumab With or Without Ipilimumab in Patients With Metastatic or Unresectable Sarcoma

Status Completed

Clinical Trial Summary

This randomized phase II trial studies how well nivolumab with or without ipilimumab works in treating patients with sarcoma that has spread from the primary site to other parts of the body (metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether nivolumab works better with or without ipilimumab in treating patients with metastatic or unresectable sarcoma.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To evaluate the confirmed response rate of single agent nivolumab and dual agent nivolumab plus ipilimumab in patients with locally advanced/unresectable or metastatic soft tissue sarcoma.

SECONDARY OBJECTIVES:

I. To evaluate adverse event rates (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]4.0) within each treatment arm.

II. To evaluate duration of response, clinical benefit rate, time to progression, progression-free survival, and overall survival within each treatment arm.

CORRELATIVE SCIENCE OBJECTIVES:

I. To potentially detect an early signal of confirmed response rate within a histologically defined patient cohort.

II. To assess the potential association between programmed cell death 1 ligand 1 (PD-L1) expression (by immunohistochemistry [IHC]) and clinical outcome, within each treatment.

III. To evaluate associations between selected biomarker measured in serial peripheral blood and with clinical efficacy, within each treatment.

IV. To evaluate the association between selected biomarker measured in tumor tissue with clinical efficacy, within each treatment.

V. To evaluate the association between baseline tumor mutational burden and neoantigen production with clinical efficacy within each treatment.

EXPLORATORY PHASE II OBJECTIVES (CROSSOVER TREATMENT):

I. To evaluate secondary endpoints within patients crossing over to dual agent nivolumab plus ipilimumab after experiencing progressive disease while receiving single agent nivolumab.

II. To evaluate correlative science objectives endpoints within patients crossing over to dual agent nivolumab plus ipilimumab after experiencing progressive disease while receiving single agent nivolumab.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress after 10 weeks on single agent nivolumab may elect to cross over to Arm II.

ARM II: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.

After completion of study treatment, patients are followed up at 4 weeks and then every 6 months 3 years. ;

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors
• Histiocytoma, Malignant Fibrous
• Liposarcoma
• Locally Advanced Bone Sarcoma
• Locally Advanced Soft Tissue Sarcoma
• Metastatic Bone Sarcoma
• Metastatic Liposarcoma
• Metastatic Soft Tissue Sarcoma
• Metastatic Undifferentiated Pleomorphic Sarcoma
• Metastatic Unresectable Sarcoma
• Osteosarcoma
• Pleomorphic Liposarcoma
• Sarcoma
• Stage III Bone Sarcoma AJCC v7
• Stage III Soft Tissue Sarcoma AJCC v7
• Stage IV Bone Sarcoma AJCC v7
• Stage IV Soft Tissue Sarcoma AJCC v7
• Stage IVA Bone Sarcoma AJCC v7
• Stage IVB Bone Sarcoma AJCC v7
• Unresectable Bone Sarcoma
• Unresectable Liposarcoma
• Unresectable Soft Tissue Sarcoma

• NCT number: NCT02500797
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 2
• Start date: August 13, 2015
• Completion date: April 1, 2023