SARC038: Phase 2 Study of Regorafenib and Nivolumab in Osteosarcoma

NCT04803877 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: SARC038
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 8

Brief Summary

A phase 2 study of regorafenib in combination with nivolumab in patients with refractory or recurrent osteosarcoma.

Conditions

Osteosarcoma; Osteosarcoma in Children; Osteosarcoma Recurrent; Osteosarcoma Metastatic

Outcome Measures

Primary Outcomes (1)

• Compare the 4-month progression-free survival rate to historical controls

  To compare the 4-month progression-free survival (PFS) rate in patients with relapsed or refractory osteosarcoma administered regorafenib in combination with nivolumab to historical controls who received regorafenib alone, as per iRECIST. PFS will be determined as the time from the start of study treatment (Cycle 1, Day 1) to time of disease relapse, disease progression, or death from any cause, using iRECIST. The proportion of patients who do not experience one of these events at 4 months will be determined.

  Approximately 4 months

Secondary Outcomes (5)

• Objective Response Rate

  Approximately 5 years

• Progression-Free Survival

  Approximately 5 years

• Progression-Free Survival and Objective Response Rate

  Approximately 5 years

• Describe adverse events

  Approximately 5 years

• Estimate 1-year and 2-year Overall Survival

  Approximately 5 years

Study Arms (1)

Regorafenib and Nivolumab

EXPERIMENTAL

Drug: Regorafenib 40 MG; Drug: Regorafenib 20MG; Drug: Nivolumab

Interventions

Regorafenib 40 MG DRUG

For subjects age 18 and older, Regorafenib will be administered as 80mg oral once daily on Cycle 1, Days 1-7 and then escalated to 120 mg once daily for Cycle 1, Days 8-21 if no Grade 2 or above regorafenib adverse events occur. For subsequent cycles, the highest tolerated dose will be taken once daily on days 1-21 of each 28-day cycle.

Regorafenib and Nivolumab

Regorafenib 20MG DRUG

For subjects younger than 18 years, Regorafenib will be administered as 60mg/m2/dose (rounded to the nearest 20mg, maximum dose of 80mg) once daily for Cycle 1, Days 8-21 if no Grade 2 or above regorafenib-related adverse events occur. For subsequent cycles, the highest tolerated dose will be taken once daily on days 1-21 of each 28-day cycle.

Regorafenib and Nivolumab

Nivolumab DRUG

For subjects age 18 and older, Nivolumab will be administered at 480mg IV over 30 min every 28 days. For subjects younger than 18 years, Nivolumab 3mg/kg (maximum dose 240mg) will be administered IV over 30 minutes on day 1 and 15 of each 28-day cycle.

Regorafenib and Nivolumab

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 5 years at the time of enrollment. Every effort will be made to ensure that 50% of patients will be ≤ 21 years of age.
• Histologically confirmed high grade osteosarcoma (excluding osteosarcoma associated with Paget disease of bone or extraskeletal osteosarcoma) at diagnosis or relapse.
• Must have relapsed or refractory osteosarcoma following at least one line of systemic therapy for the initial treatment of osteosarcoma.
• Performance Status: Lansky (≤ 16 years of age) or Karnofsky (\>16 years of age) performance score of ≥ 70, or Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1. See Appendix A. Patients who are unable to walk because of paralysis, but who are up and about in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• At least one site of measurable disease on CT/MRI scan as defined by RECIST 1.1. Baseline imaging must be performed within 21 days of Day 1 of study therapy.
• Must be able to swallow intact pills
• Adequate organ and bone marrow function within 7 days of Day 1 of study therapy defined as:
• Absolute Neutrophil Count (ANC) ≥ 1000/mm3
• Platelets ≥ 75 000/mm3
• Hemoglobin ≥ 8 g/ dL (transfusions allowed)
• ALT and AST ≤ 3 x institutional upper limit of normal (ULN) or ≤ 5.0 x institutional ULN if considered due to tumor
• Serum albumin ≥ 3 g/dL
• Serum total bilirubin ≤ 1.5 x institutional ULN. NOTE: Patients with elevated bilirubin secondary to Gilbert's disease are eligible to participate in the study
• Serum creatinine ≤ 3 x institutional ULN or 24-hour creatinine clearance ≥ 30 ml/min (calculated creatinine clearance using Cockcroft formula is acceptable)
• Normal free T4. Replacement therapy allowed.

You may not qualify if:

• Patients with prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen in this trial.
• Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
• Major surgery (thoracotomy or laparotomy, etc.), laparoscopic biopsy, or significant traumatic injury within 28 days prior to Day 1 of study or who have not recovered adequately from prior surgery
• Women who are pregnant or nursing/breastfeeding.
• Known hypersensitivity to excipients of the formulations of regorafenib or nivolumab or similar agents
• Inability to comply with protocol required procedures
• Prior therapy with an immune checkpoint inhibitor or a tyrosine kinase inhibitor targeting VEGF
• Patients with autoimmune disease.
• Chronic use of immunosuppressive therapies
• Received any investigational drug within 28 days of study enrollment
• Uncontrolled infection
• Known active HIV. Testing is not required. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. However, strong CYP3A4 inhibitors are prohibited.
• Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• Prior allogeneic hematopoietic stem cell/bone marrow transplant or solid organ transplant
• Uncontrolled hypertension defined as on average, \> 140 systolic pressure or \> 90 diastolic pressure in patient ≥ 18 y/o or \> 95th percentile for age/gender in patients \< 18 y/o despite medical management. If blood pressure is borderline, ensure patient is properly prepared (relaxed, sitting in chair for \> 3 minutes), proper technique is used (correct cuff size and positioning), and document 2 separate recordings, each at least \>5 minutes apart.

Sponsors & Collaborators

• Sarcoma Alliance for Research through Collaboration: lead

Study Sites (8)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Cincinnati Children's

Cincinnati, Ohio, 45229, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Osteosarcoma

Interventions

regorafenib; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 18, 2021
• Study Start: June 4, 2021
• Primary Completion: November 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: October 31, 2025

Record last verified: 2025-10

Locations

US (8)