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
Overview
- Phase
- Phase 1
- Intervention
- Nivolumab
- Conditions
- Osteosarcoma
- Sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Enrollment
- 21
- Locations
- 43
- Primary Endpoint
- Phase I: Recommended Phase II Dose (RP2D)
- Status
- Active, Not Recruiting
- Last Updated
- 2 months ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
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).
Intervention: Nivolumab
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).
Intervention: Azacitidine
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).
Intervention: Post Treatment Surgery
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Percentage of Participants with Event Free Survival (EFS)(1 year post surgery)
- Overall Survival (OS) Rate(1 year post surgery)