Soft Tissue Sarcomas
Conditions
Keywords
Metastatic, Unresectable, anthracycline, chemotherapy, systemic therapy
Brief summary
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
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.
Interventions
BIOLOGICALNivolumab
Nivolumab will be given as an intravenous infusion at a dose of 240 mg every 2 weeks for at least 6 months.
DRUGPazopanib
Pazopanib given at a dose of 800 mg by mouth daily.
Sponsors
Bristol-Myers Squibb
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) at 6 months for nivolumab alone or nivolumab in combination with pazopanib | 6 Months | Time from randomization until disease progression or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure of Tolerability | 6 Months | 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) |
| Overall Response Rate | 6 Months | Proportion of patients with reduction in tumor burden of a predefined amount |
| Median Progression Free Overall Survival (OS) | 6 Months | Time from randomization until death from any cause |
Countries
United States
Outcome results
None listed