Sorafenib for Gastrointestinal Stromal Tumor

Recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Imatinib, Sunitinib

Must not be taking: Antiepileptics, St. John's wort

Disqualifiers: Brain metastases, Heart failure, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 28 days per course

38 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial is studying how well sorafenib works in treating patients with malignant gastrointestinal stromal tumor that progressed during or after previous treatment with imatinib mesylate and sunitinib malate. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as enzyme-inducing antiepileptic drugs, St. John's wort, and rifampin. You also cannot take other anticancer agents or therapies. If you are on warfarin, you can continue as long as your dose is stable and your INR is ≤3.

What data supports the effectiveness of the drug Sorafenib for treating gastrointestinal stromal tumors?

Research shows that Sorafenib can be effective for patients with gastrointestinal stromal tumors (GISTs) who have not responded to other treatments, with a clinical benefit rate of 40% and a median progression-free survival of 7.2 months. It is generally well-tolerated, with most side effects being mild to moderate. ^{1 2 3 4 5}

Is sorafenib safe for humans?

Sorafenib (Nexavar) has been associated with some side effects, including skin issues, diarrhea, fatigue, high blood pressure, and in rare cases, acute pancreatitis (inflammation of the pancreas). These side effects can often be managed with early recognition and intervention, allowing patients to continue treatment safely. ^{6 7 8 9 10}

How is the drug sorafenib different from other treatments for gastrointestinal stromal tumors?

Sorafenib is unique because it is used as a third- or fourth-line treatment for gastrointestinal stromal tumors (GISTs) when other treatments like imatinib and sunitinib have failed. It works by inhibiting multiple tyrosine kinase receptors, which are proteins involved in the growth of cancer cells, and is taken orally, making it a convenient option for patients. ^{1 2 3 11 12}

Research Team

Hedy Kindler, M.D.

Principal Investigator

University of Chicago Comprehensive Cancer Center

Eligibility Criteria

This trial is for patients with a type of cancer called gastrointestinal stromal tumor (GIST) that has worsened despite treatment with imatinib mesylate and sunitinib malate. Participants must have measurable disease, no brain metastases, acceptable organ function, controlled blood pressure, not be pregnant or nursing, and agree to use contraception. They should not have other active cancers or serious medical conditions.

Inclusion Criteria

I do not have any blockage or holes in my intestines.

I have never taken medication to stop new blood vessels from forming in my tumor.

I haven't had immunotherapy after my last dose of imatinib or sunitinib.

Exclusion Criteria

I am not taking certain seizure medications, St. John's wort, or Rifampin.

I am on warfarin, but it doesn't meet the trial's criteria.

I am on HIV medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per course

CT scans every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Periodic follow-up

Treatment Details

Interventions

• Sorafenib

Trial Overview The trial is testing the effectiveness of Sorafenib Tosylate in treating GIST that hasn't responded to standard treatments. Sorafenib aims to inhibit enzymes necessary for cancer cell growth and cut off the tumor's blood supply.

Participant Groups

Group I: Treatment (sorafenib tosylate) Experimental Treatment 1 Intervention

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Sorafenib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Nexavar for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Nexavar for:

• Renal cell carcinoma
• Hepatocellular carcinoma
• Radioactive iodine-refractory differentiated thyroid carcinoma

Approved in Canada as Nexavar for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Nexavar for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Sorafenib is an effective treatment for patients with unresectable hepatocellular carcinoma (HCC) and advanced renal cell carcinoma (RCC), and is currently being tested in various other cancers, including differentiated thyroid cancer and metastatic breast cancer.

Common side effects of sorafenib, such as skin issues, diarrhea, fatigue, and hypertension, can be managed effectively through early recognition, patient education, and communication with healthcare teams, which helps patients maintain their full dosage during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of common adverse events in patients treated with sorafenib: nurse and pharmacist perspective. Walko, CM., Grande, C.[2018]

Sorafenib is an oral kinase inhibitor that effectively targets multiple tyrosine kinases involved in cancer, including pathways like raf-ras and VEGF, which are often disrupted in tumors.

The FDA has approved sorafenib for advanced renal cell cancer and hepatocellular cancer, and it has shown promising clinical activity in thyroid cancer, with ongoing trials exploring its use in combination therapies for various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorafenib. Hasskarl, J.[2018]

References

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

Sorafenib in patients with metastatic gastrointestinal stromal tumors who failed two or more prior tyrosine kinase inhibitors: a phase II study of Korean gastrointestinal stromal tumors study group. [2022]

2. Poland pubmed.ncbi.nlm.nih.gov

The analysis of the long-term outcomes of sorafenib therapy in routine practice in imatinib and sunitinib resistant gastrointestinal stromal tumors (GIST). [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the third- or fourth-line treatment: A retrospective multicenter experience. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The BRAF Status May Predict Response to Sorafenib in Gastrointestinal Stromal Tumors Resistant to Imatinib, Sunitinib, and Regorafenib: Case Series and Review of the Literature. [2019]

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

The Landmark Series: Systemic Therapy for Resectable Gastrointestinal Stromal Tumors. [2022]

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

Acute pancreatitis associated with sorafenib. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Phase II study to investigate the efficacy, safety, and pharmacokinetics of sorafenib in Japanese patients with advanced renal cell carcinoma. [2022]

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

Dermatologic symptoms associated with the multikinase inhibitor sorafenib. [2018]

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

Management of common adverse events in patients treated with sorafenib: nurse and pharmacist perspective. [2018]

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

Sorafenib. [2018]

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

Sorafenib induces growth suppression in mouse models of gastrointestinal stromal tumor. [2022]

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

The role of adjuvant and neoadjuvant therapy in gastrointestinal stromal tumors. [2021]