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

NCT03006848 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: OSTPDL1Pfizer W1211733 (OSTPDL1)Gateway RESAG
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 4

Brief Summary

This clinical trial seeks to determine if avelumab will be effective in facilitating removal of all gross tumor in the event of a relapse of osteosarcoma in pediatric patients. Avelumab will be evaluated using dosing that has previously been determined in adult studies. Primary Objectives:

• To estimate the response rate to 4 cycles of avelumab in patients with recurrent or progressive osteosarcoma.
• To estimate the 16-week progression free survival of patients with recurrent or progressive osteosarcoma after treatment with avelumab. Secondary Objective:
• To describe the toxicities associated with the administration of avelumab in patients with recurrent or progressive osteosarcoma.
• 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. Exploratory Objectives:
• To explore factors associated with response in patients treated with avelumab after recurrent or progressive osteosarcoma (e.g. tumor PD-L1 expression).
• To measure parameters of immune activation including subsets of peripheral blood mononuclear cells (PBMCs) and serum markers of immune activation.
• 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.

Conditions

Osteosarcoma

Keywords

Osteosarcoma; PD-L1; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Response Rate

  The study is designed by treating RECIST response \[complete response + partial response (CR+PR)\] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.

  At the end of 4 cycles of avelumab (approximately 4 months)

• Progression-free Survival

  The study is designed by treating RECIST response \[complete response + partial response (CR+PR)\] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.

  At the end of 4 cycles of avelumab (approximately 4 months)

Secondary Outcomes (1)

• Target Toxicities

  At the end of treatment (up to 2 years after enrollment of last participant)

Other Outcomes (5)

• Factors Associated With Response

  Following completion of therapy for last participant (up to 2 years after enrollment)

• Change in Parameters of Immune Activation

  Baseline prior to start of therapy and following 2 cycles of therapy (up to 8 weeks after last enrollment)

• Change in Cell Proliferation

  Baseline prior to start of therapy and after completion of therapy (approximately 2 years after last participant enrollment).

Study Arms (1)

Avelumab

EXPERIMENTAL

All participants with recurrent/refractory osteosarcoma who consent to the study. Interventions: Avelumab and quality of life questionnaires.

Drug: Avelumab; Other: Questionnaires

Interventions

Avelumab DRUG

Patients will be administered avelumab at a dose of 10 mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting 28 days. Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26 cycles.

Also known as: MSB0010718C, anti-PD-L1

Avelumab

Questionnaires OTHER

To assess quality of life, patients will complete questionnaires at four time points.

Also known as: PROMIS Pediatric Profile, PROMIS Adult Profile

Avelumab

Eligibility Criteria

• Age: 12 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.
• Organ Function Requirements:
• Adequate bone marrow function defined as:
• Peripheral absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3 (transfusion independent)

You may not qualify if:

• 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., 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 HIV or known acquired immunodeficiency syndrome.
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV 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 CTCAE v4.03 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, see Appendix 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Pfizer: collaborator
• Gateway for Cancer Research: collaborator

Study Sites (4)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

St Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Children's Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

  PMID: 31401903 DERIVED

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Osteosarcoma

Interventions

avelumab; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Limitations and Caveats

One patient changed administration schedule for C2D15 in cycle 2 due to family vacation plan. The variance in dates was submitted to IRB and the patient was approved to continue on treatment when returns from the trip. One patient was unable to travel from Puerto Rico due to hurricane devastation. Dose C2D15 skipped in cycle 2. Medications were given one or two day(s) earlier or later than the scheduled date for a few patients.

Results Point of Contact

• Title: Dr. Michael Bishop
• Organization: St Jude Children's Research Hospital

referralinfo@stjude.org

866-278-5833

Study Officials

• Michael W. Bishop, MD, MS

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2016
• First Posted: December 30, 2016
• Study Start: February 16, 2017
• Primary Completion: March 18, 2020
• Study Completion: March 18, 2020
• Last Updated: February 23, 2026
• Results First Posted: September 16, 2021

Record last verified: 2026-02

Locations

US (4)