Avelumab in Treating Patients with Recurrent or Progressive Osteosarcoma

Status: Active

Description

This phase II trial studies how well avelumab works in treating patients with osteosarcoma that has come back or is growing, spreading, or getting worse. Monoclonal antibodies, such as avelumab, may interfere with the ability of tumor cells to grow and spread.

Eligibility Criteria

Inclusion Criteria

  • 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 * Myelosuppressive chemotherapy: must not have received within 3 weeks of entry onto this study * Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent * 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) * 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
  • Peripheral absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 100,000/mm^3 (transfusion independent)
  • Hemoglobin >= 9.0 g/dL (may receive red blood cell [RBC] transfusions)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR
  • Serum creatinine based on age/gender as follows: (threshold creatinine values were derived from the Schwartz formula for estimating GFR) * 12 to < 13 years; 1.2 mg/DL (male and female) * 13 to < 16 years; 1.5 mg/DL (male) and 1.4 mg/DL (female) * >= 16 years; 1.7 mg/DL (male) and 1.4 mg/DL (female)
  • Total bilirubin =< 1.5 x the institutional upper limit of normal (IULN) for age
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [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
  • Serum lipase =< upper limit of normal (IULN)
  • 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, National Cancer Institute (NCI), Food and Drug Administration (FDA) and Office for Human Research Protections (OHRP) guidelines

Exclusion Criteria

  • Central nervous system (CNS) metastases
  • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent; c. steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)
  • Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent; patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible
  • Active infection requiring systemic therapy
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
  • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV ribonucleic acid [RNA] if anti-HCV antibody screening test positive)
  • Patient who has received vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines
  • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI Common Terminology Criteria for Adverse Events [CTCAE] version [v]4.03 grade >= 3)
  • Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification class II), or serious cardiac arrhythmia requiring medication
  • Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 grade > 1); however, alopecia, sensory neuropathy grade =< 2, or other grade =< 2 not constituting a safety risk based on investigator’s judgment are acceptable
  • Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
  • Patients with active diarrhea > CTCAE v4.03 grade 2
  • Patients who have previously received a prior organ transplantation, including allogeneic stem cell transplantation
  • Female patients who are pregnant or actively breastfeeding
  • Patients who have previously received anti-PD1 or anti-PD-L1 therapy; patients who have previously received anti-CTLA-4 therapy (e.g. ipilimumab) are eligible for study

Locations & Contacts

California

Los Angeles
Children's Hospital Los Angeles
Status: Active
Contact: Leo Mascarenhas
Phone: 323-361-6058

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Filemon Sorillo Dela Cruz
Phone: 212-639-7202
Email: delacrf1@mskcc.org

Tennessee

Memphis
St. Jude Children's Research Hospital
Status: Active
Contact: Michael William Bishop
Phone: 901-595-6407
Email: Michael.Bishop@stjude.org

Texas

Houston
Texas Children's Hospital
Status: Active
Contact: Sarah Brackley Whittle
Phone: 832-824-4822

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To estimate the response rate to 4 cycles of avelumab in patients with recurrent or progressive osteosarcoma.

II. To estimate the 16-week progression free survival of patients with recurrent or progressive osteosarcoma after treatment with avelumab.

SECONDARY OBJECTIVES:

I. To describe the toxicities associated with the administration of avelumab in patients with recurrent or progressive osteosarcoma.

EXPLORATORY OBJECTIVES:

I. To explore factors associated with response in patients treated with avelumab after recurrent or progressive osteosarcoma (e.g. tumor PD-L1 expression).

II. To measure parameters of immune activation including subsets of peripheral blood mononuclear cells (PBMCs) and serum markers of immune activation.

III. To evaluate the role of T-cells in immune checkpoint blockade via measures of cell proliferation, co-inhibitory receptor expression on CD8 T cells, T cell repertoire, and epigenetic programming.

IV. To assess the quality of life of patients with recurrent or progressive osteosarcoma undergoing treatment with avelumab, and to explore relationships between clinical factors and patient-reported health-related quality of life (HRQOL) outcomes.

OUTLINE:

Patients receive avelumab intravenously (IV) over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 90 days.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
St. Jude Children's Research Hospital

Principal Investigator
Michael William Bishop

Trial IDs

Primary ID OSTPDL1
Secondary IDs NCI-2016-02036
Clinicaltrials.gov ID NCT03006848