OsteosarcomaPhase 2NCT04803877
SARC038: Phase 2 Study of Regorafenib and Nivolumab in Osteosarcoma
A Phase 2 study testing Regorafenib 40 MG, Regorafenib 20MG and Nivolumab in people with Osteosarcoma and Osteosarcoma in Children, run by Sarcoma Alliance for Research through Collaboration at 8 sites in United States.
Trial summary
A phase 2 study of regorafenib in combination with nivolumab in patients with refractory or recurrent osteosarcoma. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Osteosarcoma, Osteosarcoma in Children, Osteosarcoma Recurrent
- What is being tested?
- Regorafenib 40 MG, Regorafenib 20MG and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 8 sitesUnited States
- Study dates
- 4 Jun 2021to Jun 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
- No congestive heart failure (CHF) worse than New York Heart Association Functional Classification Class I.
- No clinically significant cardiac arrhythmias, stroke or myocardial infarction within 6 months prior to enrollment.
- Prior Therapy: All prior treatment-related toxicities must have resolved to ≤ Grade 1 or be determined clinically stable by the Investigator.
- Myelosuppressive chemotherapy: Patients must not have received myelosuppressive chemotherapy within 3 weeks of enrollment
- Hematopoietic growth factors: At least 7 days must have elapsed since the completion of therapy with a white blood cell or platelet growth factor. At least 14 days must have elapsed after receiving pegfilgrastim.
- Biologic (anti-neoplastic agent): At least 7 days must have elapsed since completion of therapy with a biologic agent.
- Monoclonal antibodies: At least 21 days must have elapsed since prior therapy that included a monoclonal antibody (e.g., dinutuximab, denosumab, bevacizumab).
- Radiotherapy: ≥ 2 weeks must have elapsed since local palliative XRT (small port); ≥ 3 months must have elapsed if prior craniospinal XRT was received, if ≥ 50% of the pelvis was irradiated, or if TBI was received; ≥ 6 weeks must have elapsed if other substantial bone marrow irradiation was given.
- Autologous Stem Cell Transplant or Rescue or Cellular Therapy: ≥ 2 months must have elapsed since transplant/cellular therapy.
- Voluntary, written informed consent
- Negative urine or serum pregnancy test in women of childbearing potential. Women of childbearing potential includes pre-menarchal girls with evidence of puberty onset, and adult women through the end of the first 2 years of the onset of menopause. Testing should be completed ≤ 7 days prior to Day 1 of study.
- Fertile men and women of childbearing potential must agree to use an effective method of birth control from Day 1 of study and for 5 months after last dose of nivolumab or for 8 weeks after last dose of regorafenib, whichever is longer.
- Effective methods of birth control include: surgical sterility (subject or subject's partner), barrier device (condom, diaphragm), contraceptive coil (IUD), abstinence, or oral contraception.
- Patients with central nervous system (CNS) disease are eligible if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of progression for at least 4 weeks after CNS therapy.
- Patients >18 years must be willing to undergo tumor biopsy at study entry and post-treatment biopsy for biologic correlates. If biopsy is contra-indicated, enrollment must be approved by study PI and archival tissue must be available.
Who cannot join
- 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
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- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Michigan
Ann Arbor, Michigan, 48109
Johns Hopkins
Baltimore, Maryland, 21287
Cincinnati Children's
Cincinnati, Ohio, 45229
UT Southwestern Medical Center
Dallas, Texas, 75390
Children's Hospital of Los Angeles
Los Angeles, California, 90027
University of Miami
Miami, Florida, 33136
University of Minnesota
Minneapolis, Minnesota, 55455
Oregon Health and Sciences University
Portland, Oregon, 97239
About this study
Official title: SARC038: A Phase 2 Study of Regorafenib in Combination With Nivolumab in Patients With Refractory or Recurrent Osteosarcoma
A phase 2 study of regorafenib in combination with nivolumab in patients with refractory or recurrent osteosarcoma.
Read the detailed description
This is a single arm, Simon two-stage historically controlled study to compare the 4 month progression-free survival rate of patients with relapsed/refractory osteosarcoma treated with regorafenib in combination with nivolumab to those who received regorafenib alone (historical control).
- Being tested
- Regorafenib 40 MG, Regorafenib 20MG, Nivolumab
- Medical subject headings
- Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regorafenib 40 MGDrug
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 20MGDrug
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.
NivolumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib and Nivolumab | Experimental | Not described Receives: Drug: Regorafenib 40 MG; Drug: Regorafenib 20MG; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Approximately 4 months
Secondary outcomes (5)
Objective Response Rate
To estimate the objective response rate (ORR) in patients with relapsed or refractory osteosarcoma administered regorafenib in combination with nivolumab, according to iRECIST. Objective tumor response, defined as achievement of nadir response of complete response (CR) or partial response (PR) by iRECIST without prior progression any time during protocol therapy.
Measured: Approximately 5 years
Progression-Free Survival
To estimate the PFS, including median PFS, in this population. Progression-free survival (PFS) defined as the time from study entry to disease relapse, disease progression, or death from any cause, using iRECIST. Patients without an event will be censored at the time of last disease follow-up.
Measured: Approximately 5 years
Progression-Free Survival and Objective Response Rate
To compare the 4-month PFS rate and ORR to historical controls in this population, according to RECIST 1.1. Duration of response is defined as the time from a nadir tumor response of CR/PR to disease progression.
Measured: Approximately 5 years
Describe adverse events
To describe the toxicities of regorafenib in combination with nivolumab in patients with relapsed or refractory osteosarcoma. Adverse events will be graded as defined in CTCAE v. 5.0 during each therapy course.
Measured: Approximately 5 years
Estimate 1-year and 2-year Overall Survival
To estimate 1-year and 2-year overall survival (OS) in patients with relapsed or refractory osteosarcoma treated with regorafenib in combination with nivolumab. Overall survival, defined as the time from study entry to death from any cause. Patients who are alive at the time of analysis will be censored at the date of last follow-up.
Measured: Approximately 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2021
- Study start4 Jun 2021
- Primary completionNov 2025 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sarcoma Alliance for Research through Collaboration
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04803877
- Sponsor's protocol ID
- SARC038
- Status last verified
- Oct 2025
- First submitted
- 11 Mar 2021
- Last updated
- 31 Oct 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SARC038: A Phase 2 Study of Regorafenib in Combination With Nivolumab in Patients With Refractory or Recurrent Osteosarcoma
- ClinicalTrials.gov ID
- NCT04803877
- Acronym / sponsor ID
- SARC038
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Sarcoma Alliance for Research through CollaborationUniversity, hospital or other
- Study start
- 4 Jun 2021 (actual)
- Primary completion
- Nov 2025 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 18 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A phase 2 study of regorafenib in combination with nivolumab in patients with refractory or recurrent osteosarcoma.
Detailed description
This is a single arm, Simon two-stage historically controlled study to compare the 4 month progression-free survival rate of patients with relapsed/refractory osteosarcoma treated with regorafenib in combination with nivolumab to those who received regorafenib alone (historical control).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib and Nivolumab | Experimental | Drug: Regorafenib 40 MG, Drug: Regorafenib 20MG, Drug: Nivolumab |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (40 listed)
- 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.
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Regorafenib 40 MGFor 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. | Drug | Regorafenib and Nivolumab |
| Regorafenib 20MGFor 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. | Drug | Regorafenib and Nivolumab |
| NivolumabFor 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. | Drug | Regorafenib and Nivolumab |
Primary outcome
Compare the 4-month progression-free survival rate to historical controls
Time frame: Approximately 4 months
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.
5 secondary outcomes
Objective Response Rate
Time frame: Approximately 5 years
Progression-Free Survival
Time frame: Approximately 5 years
Progression-Free Survival and Objective Response Rate
Time frame: Approximately 5 years
Describe adverse events
Time frame: Approximately 5 years
Estimate 1-year and 2-year Overall Survival
Time frame: Approximately 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Regorafenib 40 MG, Regorafenib 20MG and Nivolumab in people with Osteosarcoma and Osteosarcoma in Children, run by Sarcoma Alliance for Research through Collaboration at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 40 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 31 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Compare the 4-month progression-free survival rate to historical controls (time frame: Approximately 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2025.