Nivolumab, Ipilimumab and Pazopanib Hydrochloride in Treating Patients with Locally Unresectable or Metastatic Soft Tissue or Bone Sarcomas

Inclusion Criteria

• Ability to understand and willingness to sign a written informed consent.
• Histologic diagnosis of metastatic or locally unresectable soft tissue or bone sarcoma.
• Progressed after at least one line of systemic therapy.
• Any prior therapy is permitted except prior therapy with nivolumab, ipilimumab and pazopanib.
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1.
• Patients must have at least 2 distinct measurable metastatic sites, with one of at least 1 cm or larger in its largest diameter and may have additional non-measurable but established metastatic lesions (i.e. bone metastases).
• White blood count (WBC) >= 2000/uL.
• Absolute neutrophil count (ANC) >= 1000/uL.
• Platelets >= 75 x 10^3/uL.
• Hemoglobin >= 8 g/dL.
• Creatinine =< 1.5 x upper limit of normal (ULN).
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN for patients without liver metastasis.
• Bilirubin =< 3.0 x ULN.
• Life expectancy > 3 months.
• In case of brain metastases, stable disease for at least 4 weeks and no steroid dependency after treatment.
• Women of childbearing potential must agree to use an adequate method of contraception (as listed in the consent form) throughout treatment and for at least 5 months after study drugs are stopped. Male participants with female partners of child bearing potential must agree to use adequate contraception (as listed in the consent form) throughout treatment and for at least 7 months after study drugs are stopped.
• Patients who are known to be human immunodeficiency virus (HIV)-positive are eligible if CD4+ cell count is >= 250 cells/mm^3; if patient is on antiretroviral therapy, there must be no significant interaction with nivolumab, ipilimumab and pazopanib; no history of non-malignancy acquired immunodeficiency syndrome (AIDS)-defining conditions other than low CD4+ count.

Exclusion Criteria

• Autoimmune disease: patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic autoimmune disease such as rheumatoid arthritis, systemic progressive sclerosis/scleroderma, systemic lupus erythematosus, autoimmune vasculitis/Wegener’s granulomatosis. Those with treated thyroid dysfunction, vitiligo or treated diabetes mellitus are eligible.
• 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, such as a condition associated with frequent diarrhea.
• Concomitant therapy with any non-study immunotherapy regimens, cytotoxic chemotherapy, immunosuppressive agents, other investigation therapies or chronic use of systemic corticosteroids with a prednisone equivalent dose of greater than 10 mg daily.
• 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. Male participants with female partners of child bearing potential who do not agree to use adequate contraception throughout treatment and for at least 7 months after study drugs are stopped.
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
• Subjects with active hepatitis B virus (HBV), hepatitis C virus (HCV) infection or history of severe hypersensitivity reactions to monoclonal antibody therapy. Patients with previously treated HBV or HCV that have an undetectable viral load and no residual hepatic impairment are eligible.