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

NCT ID: NCT03628209

Last Updated: 2025-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-03

Study Completion Date

2025-12-31

Brief Summary

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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

Detailed Description

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Treatment will be administered in 28 day cycles with the first cycle in the neoadjuvant setting. This will be followed by surgery to render the participant in surgical remission. Subsequently the participant will continue to receive treatment for up to 12 additional cycles or until recurrence, whichever occurs first. For participants with known bilateral lung recurrence, the nodule\[s\] in one lung should be resected, prior to the first cycle of chemotherapy. This trial was initially designed as a Phase 1/2 study; However, phase 2 will not proceed.

Conditions

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Osteosarcoma Osteosarcoma in Children Osteosarcoma Recurrent Sarcoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Phase Ib lead-in with extension to Phase II
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation, Resection, Dose Expansion

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).

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

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

Azacitidine

Intervention Type 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).

Post Treatment Surgery

Intervention Type PROCEDURE

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

Interventions

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Nivolumab

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

Intervention Type DRUG

Azacitidine

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).

Intervention Type DRUG

Post Treatment Surgery

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

Intervention Type PROCEDURE

Other Intervention Names

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Opdivo® Vidaza® Standard of Care Resection of disease

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Safety and Monitoring: Patients who are considered unable to comply with the safety monitoring requirements of the study are not eligible
* Patients with known HIV or hepatitis B or C are excluded
* Patients who have received prior solid organ transplantation are not eligible
* Patients who have received prior anti-PD-1 directed therapy (mAb or small molecule) are not eligible
Maximum Eligible Age

39 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Patrick A. Thompson, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Mihaela M Druta, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

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

Los Angeles, California, United States

Site Status

Children's Hospital of Colorado

Aurora, Colorado, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Alfred I DuPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Shand's Hospital for Children at the University of Florida

Gainesville, Florida, United States

Site Status

Nemours Children's Hospital

Jacksonville, Florida, United States

Site Status

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Nemours Children's Clinic

Orlando, Florida, United States

Site Status

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status

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

Tampa, Florida, United States

Site Status

University of Kentucky, Markey Cancer Center

Lexington, Kentucky, United States

Site Status

Johns Hopkins University, Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status

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

Chapel Hill, North Carolina, United States

Site Status

Carolina Medical Center, Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Duke Health

Durham, North Carolina, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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CA209-9WW

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-19487

Identifier Type: -

Identifier Source: org_study_id

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