Study of Nivolumab With or Without Pazopanib in Metastatic or Unresectable Soft Tissue Sarcomas

Phase II Randomized Study of Nivolumab With or Without Pazopanib in Metastatic or Unresectable Soft Tissue Sarcomas After One Prior Line of Systemic Therapy or Ineligible to Receive an Anthracycline-based Treatment

This trial will assess whether nivolumab alone or nivolumab combined with pazopanib will be associated with an improvement in progression free survival (PFS) at 6 months

Study Overview

• Status: Withdrawn
• Conditions: Soft Tissue Sarcomas
• Intervention / Treatment: Biological: Nivolumab; Drug: Pazopanib

Detailed Description

The investigators hypothesize that the nivolumab alone or nivolumab plus pazopanib will be associated with an improvement in progression free survival (PFS) at 6 months compared to historical controls of placebo and pazopanib alone respectively.

This is a randomized, Phase 2 study of nivolumab alone or nivolumab plus pazopanib in adult (≥ 18 years old) male and female subjects with unresectable or metastatic soft tissue sarcoma either ineligible to receive an anthracycline-based first line treatment or after one prior systemic therapy. Up to 33 and 46 subjects will be randomized (1:1) in the nivolumab and nivolumab plus pazopanib cohorts respectively, with a Simon two-stage design. Preliminary endpoint analysis will be performed when at least 18 subjects in the nivolumab cohort and 16 subjects in the nivolumab plus pazopanib cohort, have completed the first 12 cycles of nivolumab (6 months). Accrual duration is expected to be around 2 years.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologic diagnosis of metastatic or unresectable soft tissue or bone sarcoma
• No prior therapy with nivolumab in either cohorts or with pazopanib in the combination cohort
• At least one line of systemic therapy or ineligibility for an anthracycline based chemotherapy
• At least 2 distinct measurable metastatic sites
• Adequate organ and marrow function as defined by initial laboratory tests
• Life expectancy > 3 months
• Stable brain metastases for at least 4 weeks and no steroid dependence

Exclusion Criteria:

• Autoimmune disease Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drugs hazardous or obscure the interpretation of adverse events
• Concomitant therapy with any non-study immunotherapy regimens, cytotoxic chemotherapy, immunosuppressive agents, other investigation therapies Chronic use of systemic corticosteroids greater than prednisone 10 mg daily or its equivalent
• Women of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 5 months after cessation of study drug, or have a positive pregnancy test at baseline, or are pregnant or breastfeeding;
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab; Nivolumab will be given as an intravenous infusion at a dose of 240 mg every 2 weeks for at least 6 months.	Biological: Nivolumab; Nivolumab will be given as an intravenous infusion at a dose of 240 mg every 2 weeks for at least 6 months.; Other Names: Opdivo
Experimental: Nivolumab with Pazopanib; Pazopanib at a dose of 800mg by mouth daily.	Biological: Nivolumab; Nivolumab will be given as an intravenous infusion at a dose of 240 mg every 2 weeks for at least 6 months.; Other Names: Opdivo; Drug: Pazopanib; Pazopanib given at a dose of 800 mg by mouth daily.; Other Names: Votrient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) at 6 months for nivolumab alone or nivolumab in combination with pazopanib	Time from randomization until disease progression or death	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of Tolerability	Time from randomization to disease progression, death, or discontinuation of treatment for any reason (eg, toxicity, patient preference, or initiation of a new treatment without documented progression)	6 Months
Overall Response Rate	Proportion of patients with reduction in tumor burden of a predefined amount	6 Months
Median Progression Free Overall Survival (OS)	Time from randomization until death from any cause	6 Months

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Luca Paoluzzi, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2017
• Primary Completion (Actual): August 17, 2017
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: April 27, 2017
• First Submitted That Met QC Criteria: May 9, 2017
• First Posted (Actual): May 11, 2017

Study Record Updates

• Last Update Posted (Actual): August 22, 2017
• Last Update Submitted That Met QC Criteria: August 17, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: chemotherapy; Metastatic; Unresectable; systemic therapy; anthracycline
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: 16-02078

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No