Nivolumab or Nivolumab and Azacitidine in Patients With Recurrent, Resectable Osteosarcoma
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|ClinicalTrials.gov Identifier: NCT03628209|
Recruitment Status : Recruiting
First Posted : August 14, 2018
Last Update Posted : January 11, 2023
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|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|
|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)|
|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 :||October 3, 2019|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2023|
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 Name: 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 Name: Vidaza®
Procedure: Post Treatment Surgery
Resection surgery at end of Cycle 1 treatment, day 28-35.
- 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.
- 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.
- 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.
- Overall Survival (OS) Rate [ Time Frame: 1 year post surgery ]The percentage of participants alive at 1 year post surgery.
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|Ages Eligible for Study:||up to 39 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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
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 ClinicalTrials.gov identifier (NCT number): NCT03628209
|Contact: Jessica R Crimella, BSN, RN||813-745-6250||Jessica.Crimella@moffitt.org|
|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|
|Responsible Party:||H. Lee Moffitt Cancer Center and Research Institute|
|Other Study ID Numbers:||
CA209-9WW ( Other Identifier: Bristol-Myers Squibb Protocol # )
|First Posted:||August 14, 2018 Key Record Dates|
|Last Update Posted:||January 11, 2023|
|Last Verified:||November 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action