A Phase II Trial of Avelumab in Patients With Recurrent or Progressive Osteosarcoma

Inclusion Criteria

• •Patients must be \> 12 years of age but \< 50 years of age at the time of enrollment.
• •Patients must have histologic verification of osteosarcoma at initial diagnosis or relapse.
• •Patients must have had evidence of having relapsed, progressed or become refractory to conventional therapy.
• •Patients must have measurable disease, documented by clinical, radiographic or histologic criteria. Disease must be bi-dimensionally measurable by computed tomography (CT) or magnetic resonance imaging (MRI).
• •Patients must have a performance status of ≥ 50 using the Karnofsky scale for patients \> 16 years of age and the Lansky scale for patients ≤ 16 years of age.
• •Patients must have a life expectancy of ≥ 6 weeks.
• •Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• •1. Myelosuppressive chemotherapy: must not have received within 3 weeks of entry onto this study.
• •2. Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent.
• •3. Immunotherapies: at least 42 days must have elapsed since a prior therapy that included a monoclonal antibody or any other type of immunotherapy (e.g. chimeric antigen receptor (CAR) T cell therapy).
• •4. Radiation therapy (RT): ≥ 2 weeks for local palliative RT (small port); ≥ 6 months must have elapsed if prior craniospinal RT or if ≥ 50% radiation of the pelvis; ≥ 6 weeks must have elapsed if other substantial bone marrow (BM) radiation.
• •Organ Function Requirements:
• •1. Adequate bone marrow function defined as:
• •* Peripheral absolute neutrophil count (ANC) ≥ 1500/mm3
• •* Platelet count ≥ 100,000/mm3 (transfusion independent)
• •* Hemoglobin ≥ 9.0 g/dL (may receive RBC transfusions)
• •2. Adequate renal function defined as:
• •* Creatinine clearance or radioisotope GFR ≥70 mL/min/1.73m2 OR
• •* Serum creatinine based on age/gender as follows: (threshold creatinine values were derived from the Schwartz formula for estimating GFR).
• •* Age is: 12 to \<13 years, then maximum creatinine is 1.2 mg/DL for male and female.
• •* Age is: 13 to \<16 years, then maximum creatinine is 1.5 mg/DL for male and 1.4 mg/DL for female.
• •* Age is: ≥16 years, then maximum creatinine is 1.7 mg/DL for male and 1.4 mg/DL for female.
• •3. Adequate liver function defined as:
• •* Total Bilirubin ≤ 1.5x the institutional upper limit of normal (IULN) for age
• •* ALT (SGPT) and AST (SGOT) \< 2.5 x IULN for age (or \< 5 x IULN for patients with documented metastatic disease to the liver)
• •* Serum albumin \> 2 g/dL
• •4. Serum lipase ≤ upper limit of normal (IULN).
• •5. Patients must have documented pulse oximetry ≥ 92% on room air.
• •Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days of enrollment.
• •Male or female patients who are sexually active and of reproductive potential must agree to use an effective contraceptive method throughout the study and for at least 60 days after last avelumab treatment administration. Abstinence is an acceptable form of contraception.
• •Patients must not currently be using other investigational agents.
• •Patients must not currently be using other anti-cancer agent.
• •Patients must be able to comply with the safety monitoring of the study in the opinion of the investigator.
• •Written, informed consent and assent following Institutional Review Board, NCI, FDA and OHRP guidelines.