Nivolumab or Nivolumab and Azacitidine in Patients With Recurrent, Resectable Osteosarcoma

NCT03628209 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: MCC-19487CA209-9WW
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 22

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of nivolumab, or nivolumab in combination with azacitidine in participants with recurrent, resectable osteosarcoma

Conditions

Osteosarcoma; Osteosarcoma in Children; Osteosarcoma Recurrent; Sarcoma

Keywords

resectable osteosarcoma

Outcome Measures

Primary Outcomes (2)

• Phase I: Recommended Phase II Dose (RP2D)

  If one or fewer dose limiting toxicities (DLT's) occur in 6 participants the study will advance to the next dose level. If 2 or more DLT's occur at a dose level, the prior dose level will be identified as the RP2D.

  60 days

• Phase II: Rate of Continued Complete Remission (CR)

  Continued complete remission by computed tomography (CT) scan 1 year after surgery.

  1 year post surgery

Secondary Outcomes (2)

• Percentage of Participants with Event Free Survival (EFS)

  1 year post surgery

• Overall Survival (OS) Rate

  1 year post surgery

Study Arms (1)

Dose Escalation, Resection, Dose Expansion

EXPERIMENTAL

Participants will receive 1 cycle of neoadjuvant Nivolumab or Nivolumab + Azacitidine, followed by surgery to render them in surgical remission. Subsequently they will continue to receive Nivolumab or Nivolumab + Azacitidine for 12 additional cycles or until recurrence, whichever occurs first. Once the recommended Phase II dose (RP2D) is identified during Phase I, the Dose Expansion Phase II will be opened at this dose level. The Phase II portion of the study will consist of a maximum 33 evaluable patients (27-30 in addition to the 3-6 enrolled at RP2D on the Phase I portion).

Drug: Nivolumab; Drug: Azacitidine; Procedure: Post Treatment Surgery

Interventions

Nivolumab DRUG

Participants will be treated with Nivolumab intravenously (IV), 3 mg/kg on days 1 and 15 of each cycle.

Also known as: Opdivo®

Dose Escalation, Resection, Dose Expansion

Azacitidine DRUG

Phase I Dose Escalation - Dose level 1: NA. Dose level 2: 60 mg/m\^2. Dose level 3: 75 mg/m\^2. Phase II Expansion - Treated at recommended Phase II dose (RP2D).

Also known as: Vidaza®

Dose Escalation, Resection, Dose Expansion

Post Treatment Surgery PROCEDURE

Resection surgery at end of Cycle 1 treatment, day 28-35.

Also known as: Standard of Care, Resection of disease

Dose Escalation, Resection, Dose Expansion

Eligibility Criteria

• Age: Up to 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must have had a histologic diagnosis of osteosarcoma at original diagnosis
• Disease Status: Patients with an isolated pulmonary recurrence of osteosarcoma can be enrolled on this study.
• Any history of metastatic disease at a site other than lung would make the patient ineligible for this study.
• The patient's treating team must consider the patient's disease to be resectable and the patient must be willing to undergo resection of all disease, including any lung lesion meeting criteria for likely metastatic disease, defined as: 3 or more lesions ≥ 3 mm in diameter OR a single lesion ≥ 5 mm.
• Patients with bilateral disease are eligible provided their disease is considered resectable. Resectable pulmonary nodules are defined as nodules that can be removed without performing a pneumonectomy (e.g., nodules immediately adjacent to the main stem bronchus or main pulmonary vessels).
• Must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2, using the Karnofsky scale for patients \> 16 years of age and the Lansky scale for patients ≤ 16 years of age
• Prior Therapy: Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to the start of protocol therapy.
• Participants must have normal organ and marrow function within 7 days of starting protocol therapy
• All participants and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent/assent document
• Additional criteria may apply

You may not qualify if:

• Pregnancy or Breast Feeding
• Males and females of reproductive potential may not participate unless they have agreed to the use of, at minimum, two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective as outlined in study protocol documentation
• Concomitant Medications: Patients receiving the following are not eligible:
• Corticosteroids or other immunosuppressive medications
• Patients who are currently receiving other investigational agents or other anti-cancer therapy
• Intercurrent Illnesses: Patients with uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements
• Autoimmune disorders: Patients with a history of any Grade autoimmune disorder are not eligible.
• Asymptomatic laboratory abnormalities (e.g., ANA, rheumatoid factor, altered thyroid function studies) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder.
• Patients with ≥ Grade 2 hypothyroidism due to history of autoimmunity are not eligible. Note: Hypothyroidism due to previous irradiation or thyroidectomy will not impact eligibility
• Allergies: Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Nivolumab (e.g., another humanized antibody) or Azacitidine are not eligible

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (22)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Children's Hospital of Los Angeles, USC Norris Comprehensive Cancer Center

Los Angeles, California, 90027, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Alfred I DuPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Shand's Hospital for Children at the University of Florida

Gainesville, Florida, 32610, United States

Location

Nemours Children's Hospital

Jacksonville, Florida, 32207, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Nemours Children's Clinic

Orlando, Florida, 32806, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center

Tampa, Florida, 33612, United States

Location

University of Kentucky, Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Johns Hopkins University, Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Carolina Medical Center, Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

Duke Health

Durham, North Carolina, 27708, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Osteosarcoma; Sarcoma

Interventions

Nivolumab; Azacitidine; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Patrick A. Thompson, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Mihaela M Druta, MD

  H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase Ib lead-in with extension to Phase II

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: August 14, 2018
• Study Start: October 3, 2019
• Primary Completion: December 29, 2024
• Study Completion: April 1, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

US (22)