Clinical trial NCT03628209: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Osteosarcoma
Osteosarcoma in Children
Osteosarcoma Recurrent
Sarcoma
Keywords: resectable osteosarcoma
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-08-14
Enrollment: 21
Sex: ALL
Maximum age (years): 39
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase Ib lead-in with extension to Phase II
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Phase I: Recommended Phase II Dose (RP2D)
timeFrame: 60 days
measure: Phase II: Rate of Continued Complete Remission (CR)
timeFrame: 1 year post surgery
Secondary outcomes:
measure: Percentage of Participants with Event Free Survival (EFS)
timeFrame: 1 year post surgery
measure: Overall Survival (OS) Rate
timeFrame: 1 year post surgery
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles, USC Norris Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I DuPont Hospital for Children
state: Delaware
city: Gainesville
country: United States
facility: Shand's Hospital for Children at the University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami - Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center
state: Florida
city: Lexington
country: United States
facility: University of Kentucky, Markey Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University, Sidney Kimmel Cancer Center
state: Maryland
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Carolina Medical Center, Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke Health
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Patrick A. Thompson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center
name: Mihaela M Druta, MD
role: PRINCIPAL_INVESTIGATOR
References: