Sorafenib for Gastrointestinal Stromal Tumor

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the drug sorafenib (Nexavar) works for individuals with a specific type of cancer called a gastrointestinal stromal tumor, particularly if the cancer worsened after other treatments. Sorafenib aims to stop cancer growth by blocking certain enzymes and cutting off the tumor's blood supply. The trial seeks participants whose tumors worsened after using two other drugs, imatinib and sunitinib. Participants should have a tumor that doctors can measure and no serious heart issues or infections. As a Phase 2 trial, this research focuses on assessing sorafenib's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that sorafenib is likely to be safe for humans?

Research shows that sorafenib can be a safe choice for patients with gastrointestinal stromal tumors (GIST) who haven't responded to other treatments. Studies have found that most people tolerate sorafenib well. Common side effects include skin reactions on the hands and feet, tiredness, high blood pressure, and stomach pain. Most patients can manage these side effects.

The safety information comes from various studies that tested sorafenib in similar groups of patients. Many people with advanced GIST have used sorafenib after other treatments like imatinib and sunitinib didn't work, providing extensive safety data.

Overall, while side effects can occur, they are usually not severe, and many patients find sorafenib to be a safe treatment option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for gastrointestinal stromal tumors (GIST), which often include drugs like imatinib and sunitinib that target specific proteins, sorafenib offers a unique approach by inhibiting multiple kinases involved in tumor growth and blood vessel formation. This multi-targeted action is what sets sorafenib apart, potentially overcoming resistance that can develop with existing therapies. Researchers are excited about sorafenib because it could provide a new option for patients whose tumors don't respond to current treatments, offering hope for improved outcomes.

What evidence suggests that sorafenib might be an effective treatment for gastrointestinal stromal tumor?

Research has shown that sorafenib, the treatment under study in this trial, can effectively treat gastrointestinal stromal tumors (GISTs), particularly when other treatments like imatinib and sunitinib are no longer effective. One study found that sorafenib helped nearly half of the patients in some way. Another study demonstrated that sorafenib served as a good backup treatment for patients who did not respond to other options. Real-world data over ten years also confirmed its effectiveness in advanced GIST cases. Sorafenib blocks certain proteins and cuts off the blood supply to the tumor, helping to stop cancer cells from growing. ^{3 5 6 7 8}

Who Is on the Research Team?

Hedy Kindler, M.D.

Principal Investigator

University of Chicago Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3789037/

Efficacy of sorafenib in patients with gastrointestinal ... Sorafenib is an effective treatment in patients with GISTs showing a clinical benefit rate of 40.0% and an acceptable tolerability.

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)34468-0/fulltext

Clinical activity of sorafenib in patients with advanced ... Clinical activity of sorafenib in patients with advanced gastrointestinal stromal tumor bearing PDGFRA exon 18 mutation: a case series. G. Roubaud. G.

3. ascopubs.org ascopubs.org/doi/10.1200/jco.2011.29.15_suppl.10010

A phase II study of sorafenib in patients with metastatic or ... Sorafenib was effective as a salvage treatment with manageable toxicities in GIST pts who failed prior standard TKIs.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6543874/

Real-World Evidence of Patient Outcome Following Treatment ... Real-world data collected in a ten-year period confirmed the effectiveness of the use of imatinib, sunitinib, or sorafenib for the treatment of advanced GIST.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804912008088

Sorafenib as third- or fourth-line treatment of advanced ... Tyrosine kinase inhibitors (TKI) improve the outcome of patients with advanced gastrointestinal stromal tumour (GIST), but treatment failure is frequent, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5798420/

The analysis of the long-term outcomes of sorafenib ... We confirmed that many advanced GIST patients benefit from sorafenib therapy after imatinib/sunitinib failure with OS > 1 year. Keywords: ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22270258/

a phase II study of Korean gastrointestinal stromal tumors ... Results: Sorafenib was well tolerated, with hand-foot skin reaction, fatigue, hypertension, and abdominal pain being the most frequent adverse events. The ...

8. valuebasedcancer.com valuebasedcancer.com/issues/2011/april-2011-vol-2-no-2/sorafenib-active-third-line-in-refractory-gist

Sorafenib Active Third-Line in Refractory GIST Most patients had been previously treated with both available agents and were receiving sorafenib as third-line therapy. “The data demonstrate that sorafenib ...