- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03628209
Nivolumab or Nivolumab and Azacitidine in Patients With Recurrent, Resectable Osteosarcoma
February 5, 2024 updated by: H. Lee Moffitt Cancer Center and Research Institute
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
Status
Active, not recruiting
Intervention / Treatment
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
- Name: Jessica R Crimella, BSN, RN
- Phone Number: 813-745-6250
- Email: Jessica.Crimella@moffitt.org
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama at Birmingham
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California
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Los Angeles, California, United States, 90027
- Children's Hospital of Los Angeles, USC Norris Comprehensive Cancer Center
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Colorado
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Aurora, Colorado, United States, 80045
- Children's Hospital of Colorado
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Connecticut
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Hartford, Connecticut, United States, 06106
- Connecticut Children's Medical Center
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Delaware
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Wilmington, Delaware, United States, 19803
- Alfred I duPont Hospital for Children
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Florida
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Gainesville, Florida, United States, 32610
- Shand's Hospital for Children at the University of Florida
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Jacksonville, Florida, United States, 32207
- Nemours Children's Hospital
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Miami, Florida, United States, 33136
- University of Miami - Sylvester Comprehensive Cancer Center
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Orlando, Florida, United States, 32806
- Nemours Children's Clinic
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Saint Petersburg, Florida, United States, 33701
- Johns Hopkins All Children's Hospital
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Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center
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Kentucky
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Lexington, Kentucky, United States, 40536
- University of Kentucky, Markey Cancer Center
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University, Sidney Kimmel Cancer Center
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New York
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Buffalo, New York, United States, 14203
- Roswell Park Comprehensive Cancer Center
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North Carolina
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Chapel Hill, North Carolina, United States, 27599
- University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center
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Charlotte, North Carolina, United States, 28203
- Carolina Medical Center, Levine Cancer Institute
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Durham, North Carolina, United States, 27708
- Duke Health
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Ohio
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic
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Columbus, Ohio, United States, 43205
- Nationwide Children's Hospital
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt-Ingram Cancer Center
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Texas
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Dallas, Texas, United States, 75390
- University of Texas Southwestern Medical Center
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Houston, Texas, United States, 77030
- University of Texas M.D. Anderson Cancer Center
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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 |
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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).
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Participants will be treated with Nivolumab intravenously (IV), 3 mg/kg on days 1 and 15 of each cycle.
Other Names:
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:
Resection surgery at end of Cycle 1 treatment, day 28-35.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Phase I: Recommended Phase II Dose (RP2D)
Time Frame: 60 days
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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.
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60 days
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Phase II: Rate of Continued Complete Remission (CR)
Time Frame: 1 year post surgery
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Continued complete remission by computed tomography (CT) scan 1 year after surgery.
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1 year post surgery
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of Participants with Event Free Survival (EFS)
Time Frame: 1 year post surgery
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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.
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1 year post surgery
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Overall Survival (OS) Rate
Time Frame: 1 year post surgery
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The percentage of participants alive at 1 year post surgery.
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1 year post surgery
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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.
Helpful Links
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
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Disease Attributes
- Neoplasms, Bone Tissue
- Neoplasms, Connective Tissue
- Sarcoma
- Recurrence
- Osteosarcoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
- Azacitidine
Other Study ID Numbers
- MCC-19487
- CA209-9WW (Other Identifier: Bristol-Myers Squibb Protocol #)
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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