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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03628209
Recruitment Status : Recruiting
First Posted : August 14, 2018
Last Update Posted : September 24, 2019
Bristol-Myers Squibb
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

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

Condition or disease Intervention/treatment Phase
Osteosarcoma Osteosarcoma in Children Osteosarcoma Recurrent Sarcoma Drug: Nivolumab Drug: Azacitidine Procedure: Post Treatment Surgery Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 51 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Phase Ib lead-in with extension to Phase II
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 26, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

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

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).
Other Name: Vidaza®

Procedure: Post Treatment Surgery
Resection surgery at end of Cycle 1 treatment, day 28-35.
Other Names:
  • Standard of Care
  • Resection of disease

Primary Outcome Measures :
  1. 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.

  2. 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.

Secondary Outcome Measures :
  1. 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.

  2. Overall Survival (OS) Rate [ Time Frame: 1 year post surgery ]
    The percentage of participants alive at 1 year post surgery.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 39 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03628209

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Contact: Tiffany Smith (813) 269-0955 ext 480

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United States, Arizona
Phoenix Children's Hospital Not yet recruiting
Phoenix, Arizona, United States, 31867
Principal Investigator: Pooja Hingorani, M.D.         
United States, California
Children's Hospital of Los Angeles, USC Norris Comprehensive Cancer Center Not yet recruiting
Los Angeles, California, United States, 90027
Principal Investigator: Leo Mascarenhas, M.D.         
United States, Connecticut
Connecticut Children's Medical Center Not yet recruiting
Hartford, Connecticut, United States, 06106
Principal Investigator: Michael Isakoff, M.D.         
United States, Delaware
Alfred I DuPont Hospital for Children Not yet recruiting
Wilmington, Delaware, United States, 19803
Principal Investigator: Emi Caywood, M.D.         
United States, Florida
Shand's Hospital for Children at the University of Florida Not yet recruiting
Gainesville, Florida, United States, 32610
Principal Investigator: William Slayton, M.D.         
Principal Investigator: Joanne Lagmay, M.D.         
Nemours Children's Hospital Not yet recruiting
Jacksonville, Florida, United States, 32207
Principal Investigator: Eric Sandler, M.D.         
Holtz Children's Hospital at the University of Miami Not yet recruiting
Miami, Florida, United States, 33136
Principal Investigator: Matteo Trucco, M.D.         
Nemours Children's Clinic Not yet recruiting
Orlando, Florida, United States, 32806
Principal Investigator: Ramamoorthy Nagasubramanian, M.D.         
Johns Hopkins All Children's Hospital Not yet recruiting
Saint Petersburg, Florida, United States, 33701
Principal Investigator: Jonathan Metts, M.D.         
H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center Recruiting
Tampa, Florida, United States, 33612
Contact: Tiffany Smith    813-745-6250   
Principal Investigator: Mihaela M Druta, MD         
Sub-Investigator: Damon Reed, MD         
Sub-Investigator: Andrew Brohl, MD         
Sub-Investigator: Leah Clark, ARNP         
United States, Kentucky
University of Kentucky, Markey Cancer Center Not yet recruiting
Lexington, Kentucky, United States, 40536
Principal Investigator: Lars Wagner, M.D.         
United States, Maryland
Johns Hopkins University, Sidney Kimmel Cancer Center Not yet recruiting
Baltimore, Maryland, United States, 21287
Principal Investigator: Brian Ladle, M.D., Ph.D.         
Principal Investigator: Nicolas J. Llosa, M.D.         
United States, New York
Montefiore Medical Center, Albert Einstein Cancer Center Not yet recruiting
Bronx, New York, United States, 10467
Principal Investigator: David Loeb, M.D., Ph.D.         
Principal Investigator: Daniel Weiser, M.D.         
United States, North Carolina
University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center Not yet recruiting
Chapel Hill, North Carolina, United States, 27599
Principal Investigator: Patrick Thompson, M.D.         
Sub-Investigator: Ian Davis, M.D., Ph.D         
Carolina Medical Center, Levine Cancer Institute Not yet recruiting
Charlotte, North Carolina, United States, 28203
Principal Investigator: Javier Oesterheld, M.D.         
United States, Ohio
Nationwide Children's Hospital Not yet recruiting
Columbus, Ohio, United States, 43205
Principal Investigator: Bhuvana Setty, M.D.         
Principal Investigator: Timothy Cripe, M.D., Ph.D.         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Not yet recruiting
Nashville, Tennessee, United States, 37232
Principal Investigator: Scott Borinstein, M.D.         
United States, Utah
Primary Children's Hospital, Huntsman Cancer Institute Not yet recruiting
Salt Lake City, Utah, United States, 84113
Principal Investigator: Douglas Fair, M.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Bristol-Myers Squibb
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Principal Investigator: Patrick A. Thompson, M.D. University of North Carolina, Chapel Hill
Principal Investigator: Mihaela M Druta, MD H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center

Additional Information:
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT03628209     History of Changes
Other Study ID Numbers: MCC-19487
CA209-9WW ( Other Identifier: Bristol-Myers Squibb Protocol # )
First Posted: August 14, 2018    Key Record Dates
Last Update Posted: September 24, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
resectable osteosarcoma
Additional relevant MeSH terms:
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Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors