SARC038: Phase 2 Study of Regorafenib and Nivolumab in Osteosarcoma

Running, not enrolling · Phase 2

Conditions studied: Osteosarcoma, Osteosarcoma in Children, Osteosarcoma Recurrent, Osteosarcoma Metastatic

In brief

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

Key facts

Study ID

NCT04803877

Run by

Sarcoma Alliance for Research through Collaboration

People needed

48

Starts

2021-06-04

Expected to finish

2026-06-01

Last updated by the study team

2025-10-31

Who can join

Age: 5 and older. Sex: any. Healthy volunteers: not accepted.

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.
• Serum lipase ≤ 1.5 x ULN
• INR ≤ 1.5 x ULN
• Urine protein: Meets one of the following criteria: (i) urinary protein by urine dipstick is ≤ 100mg/dL or ≤ 2+ (ii) Urine Protein Creatinine(UPC) ratio <3.5 (iii) 24-hour urine protein was measured, urinary protein ≤ 3500 mg
• Adequate pulmonary function defined as:
• No evidence of dyspnea at rest
• No activity limitation due to pulmonary insufficiency
• Pulse Oximetry >92% on room air
• Adequate cardiac function defined as:
• QTc ≤ 480 msec
• Shortening fraction ≥ 27% by echocardiogram or ejection fraction ≥ 50% by gated radionuclide study or echocardiogram

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.
• History of clinically significant venous or arterial thrombotic or embolic event requiring systemic anticoagulation within 6 months of enrollment.
• Requirement of oral anticoagulant therapy with oral vitamin K antagonists (warfarin). Low-dose anticoagulants for maintenance of patency of central venous device or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin or direct oral anticoagulants is allowed, providing the event prompting treatment occurred > 6 months prior. Subjects who are prophylactically being treated with an agent such as heparin will be allowed to participate, provided no prior evidence of underlying abnormality in coagulation parameters exists.
• Presence of non-healing wound, non-healing ulcer or fracture (excluding pathologic fracture)
• Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE Grade 2 dyspnea)
• Significant currently active gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn's disease, malabsorption, or CTCAE Grade ≥ 2 diarrhea of any etiology
• Patients with history of bowel perforation or fistula formation.
• Live/attenuated vaccine administered within 30 days of enrollment
• Patients receiving or requiring strong CYP3A4 inhibitors (e.g., clarithromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's wort)
• Any hemorrhage or bleeding event CTCAE ≥ Grade 3 within 28 days of study enrollment
• Body surface area (BSA) < 0.4 m2

Where it is running

• Children's Hospital of Los Angeles — Los Angeles, California, United States
• University of Miami — Miami, Florida, United States
• Johns Hopkins — Baltimore, Maryland, United States
• University of Michigan — Ann Arbor, Michigan, United States
• University of Minnesota — Minneapolis, Minnesota, United States
• Cincinnati Children's — Cincinnati, Ohio, United States
• Oregon Health and Sciences University — Portland, Oregon, United States
• UT Southwestern Medical Center — Dallas, Texas, United States

Full record on ClinicalTrials.gov

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