Nivolumab or Nivolumab and Azacitidine in Patients With Recurrent, Resectable Osteosarcoma
- Conditions
- Osteosarcoma RecurrentSarcomaOsteosarcoma in ChildrenOsteosarcoma
- Interventions
- Registration Number
- NCT03628209
- 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
- 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. This trial was initially designed as a Phase 1/2 study; However, phase 2 will not proceed.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 21
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Participants must have had a histologic diagnosis of osteosarcoma at original diagnosis
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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).
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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
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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.
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Participants must have normal organ and marrow function within 7 days of starting protocol therapy
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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
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Additional criteria may apply
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Pregnancy or Breast Feeding
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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
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Concomitant Medications: Patients receiving the following are not eligible:
- Corticosteroids or other immunosuppressive medications
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Patients who are currently receiving other investigational agents or other anti-cancer therapy
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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
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Autoimmune disorders: Patients with a history of any Grade autoimmune disorder are not eligible.
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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.
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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
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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
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Safety and Monitoring: Patients who are considered unable to comply with the safety monitoring requirements of the study are not eligible
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Patients with known HIV or hepatitis B or C are excluded
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Patients who have received prior solid organ transplantation are not eligible
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Patients who have received prior anti-PD-1 directed therapy (mAb or small molecule) are not eligible
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dose Escalation, Resection, Dose Expansion Nivolumab 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). Dose Escalation, Resection, Dose Expansion Azacitidine 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). Dose Escalation, Resection, Dose Expansion Post Treatment Surgery 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).
- Primary Outcome Measures
Name Time Method Phase I: Recommended Phase II Dose (RP2D) 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) 1 year post surgery Continued complete remission by computed tomography (CT) scan 1 year after surgery.
- Secondary Outcome Measures
Name Time Method Percentage of Participants with Event Free Survival (EFS) 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 1 year post surgery The percentage of participants alive at 1 year post surgery.
Trial Locations
- Locations (22)
Children's Hospital of Los Angeles, USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Duke Health
🇺🇸Durham, North Carolina, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Children's Hospital of Colorado
🇺🇸Aurora, Colorado, United States
H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center
🇺🇸Tampa, Florida, United States
University of Miami - Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Johns Hopkins University, Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
Carolina Medical Center, Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Nemours Children's Hospital
🇺🇸Jacksonville, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Alfred I DuPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Nemours Children's Clinic
🇺🇸Orlando, Florida, United States
University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Shand's Hospital for Children at the University of Florida
🇺🇸Gainesville, Florida, United States
University of Kentucky, Markey Cancer Center
🇺🇸Lexington, Kentucky, United States