Phase 2 Study of Nivolumab in Solid Tumors Induced by Prior Radiation Exposure

Inclusion Criteria:

• Histologically confirmed metastatic or unresectable solid tumor which standard curative or palliative measures do not exist or are no longer effective. The primary site of the metastatic or unresectable tumor must have arisen within a previously irradiated site and be considered a radiation-induced tumor.
• Pre-treatment tumor specimen available. Patients with no available archived specimen must be willing to undergo a pre-treatment tumor biopsy.
• Measurable disease.
• Progressive disease on study entry.
• Received adjuvant or neoadjuvant chemotherapy and developed recurrent or metastatic disease within 6 months of completing therapy.
• Age >18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status <2.
• Life expectancy of greater than 3 months.
• Adequate organ and marrow function as defined below:
• White Blood Cell >2,000/per microliter
• Absolute neutrophil count >1,500/per microliter
• Platelets >100,000/per microliter
• Hemoglobin ≥9.0 g/dL
• Total bilirubin ≤1.5 times the institutional upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
• Aspartate Aminotransferase(SGOT)/Alanine Aminotransferase (SGPT) <3 X institutional ULN
• Creatinine ≤1.5 X institutional ULN OR
• Creatinine clearance >40 mL/min for patients with creatinine Levels above institutional normal (calculated using the Cockcroft-Gault formula below)
• Female Creatinine Clearance = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
• Male Creatinine Clearance = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
• Women of childbearing potential (WOCBP) and men must agree to use adequate contraception prior to study entry and for the duration of study participation and up to 31 weeks after the last dose of nivolumab.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the start of nivolumab.
• Ability to understand and the willingness to sign a written informed consent document.
• Biopsiable disease at the time of enrollment as biopsies after progression are required for participation.

Exclusion Criteria:

• Any active, known or suspected autoimmune disease.
• Requiring continuous supplemental oxygen.
• Chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or unresolved toxicity due to agents administered more than 2 weeks earlier.
• Uncontrolled brain metastases.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
• Uncontrolled inter-current illness.
• Pregnant or currently breastfeeding.
• Receiving any other anticancer therapy.
• Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA- 4 antibody therapies, any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways.
• History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating ongoing acute or chronic infection.
• Requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration.