Regorafenib + Nivolumab for Osteosarcoma

Recruiting at 8 trial locations

Overseen By SARC

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Sarcoma Alliance for Research through Collaboration

Must not be taking: Immunosuppressants, CYP3A4 inhibitors

Disqualifiers: Autoimmune disease, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments: regorafenib (a cancer drug) and nivolumab (an immunotherapy drug) for patients with osteosarcoma that has returned or is unresponsive to other treatments. Osteosarcoma, a type of bone cancer, can be difficult to treat when it doesn't respond to initial therapies. The researchers aim to determine if this combination can control the cancer's growth. Suitable candidates include those whose osteosarcoma has recurred after treatment and who can swallow pills. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot participate if you are using strong CYP3A4 inhibitors or inducers, or if you require oral anticoagulant therapy with oral vitamin K antagonists like warfarin.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using regorafenib and nivolumab together is generally safe. Studies suggest that regorafenib can benefit patients with bone sarcomas and is usually well-tolerated. Doctors can effectively manage any side effects that may occur.

Nivolumab is commonly used in cancer treatments, and its safety is well-established. Together, these treatments have helped patients live longer without their cancer worsening. While all treatments can have side effects, the evidence so far reassures their safety for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for osteosarcoma, like chemotherapy and surgery, focus on directly attacking the tumor cells or removing them. But Regorafenib and Nivolumab work differently. Regorafenib is a targeted therapy that blocks the growth of blood vessels that feed the tumor, while Nivolumab is an immunotherapy that helps the body's immune system to recognize and attack cancer cells. Researchers are excited about this combination because it could offer a two-pronged approach by both starving the tumor and boosting the immune response, potentially leading to better outcomes for patients.

What evidence suggests that this treatment might be an effective treatment for osteosarcoma?

Research has shown that regorafenib may help treat osteosarcoma, particularly in patients whose cancer has worsened despite previous treatments. Studies have found that regorafenib can slow the spread of metastatic osteosarcoma, providing some benefits to patients. In this trial, participants will receive a combination of regorafenib and nivolumab. This treatment has shown promise in extending the lives of patients with relapsed or hard-to-treat osteosarcoma. Most patients have tolerated the combination well, although some needed dose adjustments due to side effects. These findings suggest that using regorafenib and nivolumab together could be an effective option for treating stubborn or returning osteosarcoma. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for patients aged 5 and older with high-grade osteosarcoma that's come back or hasn't responded to treatment. They need measurable disease on scans, good heart and lung function, no recent major surgeries or uncontrolled diseases, and must not be pregnant. Participants should have recovered from prior treatments and agree to use birth control.

Inclusion Criteria

My lungs are working well.

I haven't had chemotherapy that lowers blood cell counts in the last 3 weeks.

My heart is functioning well.

Exclusion Criteria

You have taken a medication that is still being tested in research within the last 28 days before joining this study.

I am taking warfarin for blood thinning.

I haven't had major surgery or serious injuries in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive regorafenib in combination with nivolumab

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Regorafenib

Trial Overview The study tests the combination of Regorafenib (a cancer growth blocker) at different doses with Nivolumab (an immune system booster) in those whose osteosarcoma has resisted initial therapy. It aims to see if this combo can shrink tumors better than previous treatments.

How Is the Trial Designed?

Group I: Regorafenib and Nivolumab Experimental Treatment 3 Interventions

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Sarcoma Alliance for Research through Collaboration

Lead Sponsor

Trials

26

Recruited

2,000+

Published Research Related to This Trial

Regorafenib is an FDA-approved oral medication that targets multiple kinases involved in cancer growth and has shown survival benefits in patients with metastatic colorectal cancer after standard treatments have failed.

In addition to colorectal cancer, regorafenib significantly improves progression-free survival in patients with metastatic gastrointestinal stromal tumors (GIST) and is currently being tested in various other cancers, including renal cell carcinoma and hepatocellular carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib. Ettrich, TJ., Seufferlein, T.[2015]

In a study of 72 patients with microsatellite stable metastatic colorectal cancer, regorafenib or fruquintinib combined with sintilimab showed a median progression-free survival of 4.2 months and an overall survival of 10.5 months, indicating these combinations are viable third-line treatment options.

The treatment was generally well-tolerated, with only 15.3% of patients experiencing severe adverse events, and patients without liver metastasis showed better response rates and overall survival, suggesting they may benefit more from this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microsatellite stable metastatic colorectal cancer without liver metastasis may be preferred population for regorafenib or fruquintinib plus sintilimab as third-line or above therapy:A real-world study. Nie, C., Lv, H., Chen, B., et al.[2022]

Regorafenib is an effective oral multikinase inhibitor approved by the FDA for treating metastatic colorectal cancer in patients who have not responded to standard chemotherapy and other targeted therapies, showing significant efficacy compared to placebo in the CORRECT trial.

While regorafenib has a greater antiangiogenic effect than sorafenib, it is associated with common severe side effects such as hand-foot skin reactions, diarrhea, hypertension, and fatigue, which require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of regorafenib-related toxicities: a review. Krishnamoorthy, SK., Relias, V., Sebastian, S., et al.[2022]

A new method for measuring regorafenib and its metabolites in human plasma has been developed, showing high sensitivity and specificity, which is crucial for monitoring treatment effectiveness.

The method demonstrated excellent accuracy and precision, making it suitable for analyzing large sample sizes in clinical settings, thus supporting the safe and effective use of regorafenib in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of regorafenib (BAY 73-4506) and its major human metabolites BAY 75-7495 (M-2) and BAY 81-8752 (M-5) in human plasma by stable-isotope dilution liquid chromatography-tandem mass spectrometry. Hafner, FT., Werner, D., Kaiser, M.[2019]

Regorafenib is an oral multi-kinase inhibitor that has shown significant survival benefits in metastatic colorectal cancer and has been FDA approved for this use since 2012.

The drug also improves progression-free survival in patients with metastatic gastrointestinal stromal tumors and advanced hepatocellular carcinoma, leading to its FDA approval for these conditions as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib. Ettrich, TJ., Seufferlein, T.[2018]

In a study of 66 patients with recurrent bone tumors, regorafenib and cabozantinib showed meaningful activity, with median overall survival ranging from 8.1 to 18.2 months depending on the tumor type.

The treatment was generally well-tolerated, with 42.4% of patients requiring dose reductions due to side effects, indicating that these targeted therapies can be effective with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of tyrosine kinase inhibitors in children, adolescents and adults with relapsed or refractory bone tumours: A Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) study. Peretz Soroka, H., Vora, T., Noujaim, J., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7799443/

Randomized Double-Blind Phase II Study of Regorafenib ... We hypothesized that regorafenib would improve progression-free survival (PFS) in patients with sarcoma and report the results of the osteosarcoma cohort.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31013172/

Randomized Double-Blind Phase II Study of Regorafenib in ... The study met its primary end point, demonstrating activity of regorafenib in patients with progressive metastatic osteosarcoma.

3. withpower.com withpower.com/trial/phase-3-osteosarcoma-5-2021-96d22

Regorafenib + Nivolumab for Osteosarcoma The treatment was generally well-tolerated, with 42.4% of patients requiring dose reductions due to side effects, indicating that these targeted therapies can ...

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-13722-y

Efficacy and safety of regorafenib in the treatment of bone ... Regorafenib emerges as a promising therapeutic option for metastatic or recurrent bone sarcomas, demonstrating certain clinical benefits alongside manageable ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04803877?tab=table

SARC038: Phase 2 Study of Regorafenib and Nivolumab ... To estimate 1-year and 2-year overall survival (OS) in patients with relapsed or refractory osteosarcoma treated with regorafenib in combination with nivolumab.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01339104

Open Label Regorafenib Study to Evaluate Cardiovascular ... A phase I open-label trial evaluating the cardiovascular safety of regorafenib in patients with advanced cancer. Cancer Chemother Pharmacol. 2015 Oct;76(4): ...

7. cancertreatmentreviews.com cancertreatmentreviews.com/article/S0305-7372(20)30031-1/fulltext

Evolving role of regorafenib for the treatment of advanced ... Safety of regorafenib across tumor types. Safety data from studies of regorafenib in mCRC, GIST, and HCC, in addition to emerging evidence in ...