Description:
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
Title
- Brief Title: Nivolumab or Nivolumab and Azacitidine in Patients With Recurrent, Resectable Osteosarcoma
- 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
Clinical Trial IDs
- ORG STUDY ID:
MCC-19487
- SECONDARY ID:
CA209-9WW
- NCT ID:
NCT03628209
Conditions
- Osteosarcoma
- Osteosarcoma in Children
- Osteosarcoma Recurrent
- Sarcoma
Interventions
Drug | Synonyms | Arms |
---|
Nivolumab | Opdivo® | Dose Escalation, Resection, Dose Expansion |
Azacitidine | Vidaza® | Dose Escalation, Resection, Dose Expansion |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose Escalation, Resection, Dose Expansion | Experimental | 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). | |
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
- 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
Maximum Eligible Age: | 39 Years |
Minimum Eligible Age: | N/A |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Phase I: Recommended Phase II Dose (RP2D) |
Time Frame: | 60 days |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Percentage of Participants with Event Free Survival (EFS) |
Time Frame: | 1 year post surgery |
Safety Issue: | |
Description: | 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. |
Measure: | Overall Survival (OS) Rate |
Time Frame: | 1 year post surgery |
Safety Issue: | |
Description: | The percentage of participants alive at 1 year post surgery. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | H. Lee Moffitt Cancer Center and Research Institute |
Trial Keywords
Last Updated
August 26, 2021