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

A Phase Ib/II Study to Evaluate the Safety, Feasibility and Efficacy of Nivolumab or Nivolumab in Combination With Azacitidine in Patients With Recurrent, Resectable Osteosarcoma

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

Study Overview

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • California
      • Los Angeles, California, United States, 90027
        • Children's Hospital of Los Angeles, USC Norris Comprehensive Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital of Colorado
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children's Medical Center
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I duPont Hospital for Children
    • Florida
      • Gainesville, Florida, United States, 32610
        • Shand's Hospital for Children at the University of Florida
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Hospital
      • Miami, Florida, United States, 33136
        • University of Miami - Sylvester Comprehensive Cancer Center
      • Orlando, Florida, United States, 32806
        • Nemours Children's Clinic
      • Saint Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky, Markey Cancer Center
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University, Sidney Kimmel Cancer Center
    • New York
      • Buffalo, New York, United States, 14203
        • Roswell Park Comprehensive Cancer Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center
      • Charlotte, North Carolina, United States, 28203
        • Carolina Medical Center, Levine Cancer Institute
      • Durham, North Carolina, United States, 27708
        • Duke Health
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • University of Texas M.D. Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 39 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
Participants will be treated with Nivolumab intravenously (IV), 3 mg/kg on days 1 and 15 of each cycle.
Other Names:
  • Opdivo®
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).
Other Names:
  • Vidaza®
Resection surgery at end of Cycle 1 treatment, day 28-35.
Other Names:
  • Standard of Care
  • Resection of disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I: Recommended Phase II Dose (RP2D)
Time Frame: 60 days
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)
Time Frame: 1 year post surgery
Continued complete remission by computed tomography (CT) scan 1 year after surgery.
1 year post surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants with Event Free Survival (EFS)
Time Frame: 1 year post surgery
EFS: The time from diagnostic biopsy until the earliest of: death, local recurrence, new metastatic disease, progression of metastatic disease or secondary malignancy, or date of last contact.
1 year post surgery
Overall Survival (OS) Rate
Time Frame: 1 year post surgery
The percentage of participants alive at 1 year post surgery.
1 year post surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 3, 2019

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

August 8, 2018

First Submitted That Met QC Criteria

August 9, 2018

First Posted (Actual)

August 14, 2018

Study Record Updates

Last Update Posted (Estimated)

February 6, 2024

Last Update Submitted That Met QC Criteria

February 5, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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