Nivolumab or Nivolumab and Azacitidine in Patients With Recurrent, Resectable Osteosarcoma

Sarcoma Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03628209
• Other study ID #: MCC-19487
• Secondary ID: CA209-9WW
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: October 3, 2019
• Est. completion date: December 2024

Study information

• Verified date: February 2024
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 39 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteosarcoma
• Osteosarcoma in Children
• Osteosarcoma Recurrent
• Recurrence
• Sarcoma

Intervention

Drug:
• Nivolumab
Participants will be treated with Nivolumab intravenously (IV), 3 mg/kg on days 1 and 15 of each cycle.
• Azacitidine
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).

Procedure:
• Post Treatment Surgery
Resection surgery at end of Cycle 1 treatment, day 28-35.

Locations

Country	Name	City	State
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	Johns Hopkins University, Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Carolina Medical Center, Levine Cancer Institute	Charlotte	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke Health	Durham	North Carolina
United States	Shand's Hospital for Children at the University of Florida	Gainesville	Florida
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Nemours Children's Hospital	Jacksonville	Florida
United States	University of Kentucky, Markey Cancer Center	Lexington	Kentucky
United States	Children's Hospital of Los Angeles, USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Nemours Children's Clinic	Orlando	Florida
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center	Tampa	Florida
United States	Alfred I DuPont Hospital for Children	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: Recommended Phase II Dose (RP2D)	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.	60 days
Primary	Phase II: Rate of Continued Complete Remission (CR)	Continued complete remission by computed tomography (CT) scan 1 year after surgery.	1 year post surgery
Secondary	Percentage of Participants with Event Free Survival (EFS)	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.	1 year post surgery
Secondary	Overall Survival (OS) Rate	The percentage of participants alive at 1 year post surgery.	1 year post surgery

External Links

•   Moffitt Cancer Center Clinical Trials website