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

Trial Summary

What is the purpose of this trial?

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

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.

What data supports the effectiveness of the drug combination Regorafenib and Nivolumab for treating osteosarcoma?

Research suggests that immune-based treatments like Nivolumab, which targets the PD-1 pathway, may improve outcomes in osteosarcoma by preventing immune escape, a process that allows cancer to grow unchecked. Additionally, studies in other cancers have shown that blocking PD-1/PD-L1 interactions can enhance the immune system's ability to fight tumors. ^{1 2 3 4 5}

Is the combination of Regorafenib and Nivolumab safe for humans?

Regorafenib has been studied for safety in various cancers, including colorectal, liver, and bone cancers, and is FDA-approved for some of these conditions. It has shown survival benefits and improved progression-free survival in these studies, indicating it is generally safe for human use. Nivolumab, often used in combination with other treatments, has also been evaluated for safety in different cancer types. ^{6 7 8 9 10}

How is the drug combination of Regorafenib and Nivolumab unique for treating osteosarcoma?

The combination of Regorafenib and Nivolumab is unique for treating osteosarcoma because Regorafenib is an oral drug that targets multiple pathways involved in tumor growth, while Nivolumab is an immunotherapy that helps the immune system attack cancer cells. This combination aims to enhance treatment effectiveness by using both targeted therapy and immunotherapy approaches. ^{6 10 11 12 13}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Combination immunotherapy with α-CTLA-4 and α-PD-L1 antibody blockade prevents immune escape and leads to complete control of metastatic osteosarcoma. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

PD-1 and PD-L1 Expression in Osteosarcoma: Which Specimen to Evaluate? [2021]

3. England pubmed.ncbi.nlm.nih.gov

NGS-analysis to the rescue: dual checkpoint inhibition in metastatic osteosarcoma - a case report and review of the literature. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Translational biology of osteosarcoma. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

The Updated Status and Future Direction of Immunotherapy Targeting B7-H1/PD-1 in Osteosarcoma. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study. [2021]

7. United States 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. [2023]

8. Switzerland 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Regorafenib in patients with relapsed advanced or metastatic chordoma: results of a non-comparative, randomised, double-blind, placebo-controlled, multicentre phase II study. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Regorafenib. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Management of regorafenib-related toxicities: a review. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Regorafenib. [2015]

13. England 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. [2019]