Sorafenib +/− Radiation Therapy for Liver Cancer

Recruiting at 50 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Radiation Therapy Oncology Group

Must be taking: Sorafenib

Disqualifiers: Prior invasive malignancy, Prior sorafenib use, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 8

Duration: Up to 5 years

193 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase III trial studies sorafenib tosylate and stereotactic body radiation therapy to see how well they work compared to sorafenib tosylate alone in treating patients with liver cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Stereotactic body radiation therapy may be able to send the radiation dose directly to the tumor and cause less damage to normal tissue. Giving sorafenib tosylate together with stereotactic body radiation therapy may kill more tumor cells.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get specific guidance based on your situation.

What data supports the effectiveness of the treatment Sorafenib Tosylate combined with Radiation Therapy for liver cancer?

Sorafenib is the only drug shown to improve overall survival in advanced liver cancer, and combining it with radiation therapy may enhance its effectiveness by targeting specific pathways that help cancer resist radiation. This combination is being tested in ongoing trials, and the rationale is based on the idea that radiation can control visible tumors while Sorafenib targets hidden cancer cells. ^{1 2 3 4 5}

Is the combination of Sorafenib and radiation therapy safe for treating liver cancer?

Sorafenib, used for liver cancer, can cause side effects like skin issues, diarrhea, tiredness, and high blood pressure. Radiation therapy, when compared to Sorafenib alone, showed fewer severe side effects. It's important to manage these side effects with help from healthcare providers. ^{6 7 8 9 10}

How is the drug Sorafenib Tosylate different from other treatments for liver cancer?

Sorafenib Tosylate is unique because it is a small-molecule inhibitor that targets specific proteins involved in cancer growth and blood vessel formation, and it is the only drug shown to improve survival in advanced liver cancer. When combined with radiation therapy, it may enhance the effectiveness of radiation by targeting pathways that make cancer cells resistant to radiation, potentially improving treatment outcomes. ^{1 3 5 11 12}

Research Team

Laura Dawson

Principal Investigator

Radiation Therapy Oncology Group

Eligibility Criteria

This trial is for patients with liver cancer who have not responded to certain previous treatments and do not have severe other illnesses. They should have at least one tumor in the liver or blood vessel involvement, adequate organ function, no recent serious heart issues, and agree to use contraception. Those with a history of certain treatments like sorafenib over 60 days ago or specific radiotherapies are excluded.

Inclusion Criteria

I was diagnosed with liver cancer within the last year.

I had surgery before but still meet the study's requirements.

Appropriate for protocol entry based upon minimum diagnostic workup including history/physical examination, assessment by specialists, pre-randomization scans, Zubrod performance status, and blood work with adequate organ marrow function

Exclusion Criteria

I am HIV positive with a CD4 count below 350.

My cancer has spread directly into nearby organs.

I've had radiation therapy to my liver area before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive stereotactic body radiation therapy (SBRT) in 5 fractions over 5-15 days

1-2 weeks

5 visits (in-person)

Treatment

Participants receive sorafenib tosylate, starting with 200 mg twice a day, increasing to 400 mg twice a day if tolerable, for 28-day cycles

Up to 5 years

Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

7.6 years

Every 3 months for 2 years, then every 6 months

Treatment Details

Interventions

• Sorafenib Tosylate
• Stereotactic Body Radiation Therapy

Trial Overview The study is testing if adding stereotactic body radiation therapy (SBRT) to sorafenib treatment provides better outcomes than sorafenib alone for liver cancer patients. SBRT targets tumors precisely with high-dose radiation while sparing healthy tissue. The trial randomly assigns participants to either combined treatment or just the drug.

Participant Groups

Group I: SBRT followed by Sorafenib Experimental Treatment 2 Interventions

27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.

Group II: Sorafenib Alone Active Control 1 Intervention

400 mg sorafenib twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Radiation Therapy Oncology Group

Lead Sponsor

Trials

191

Recruited

64,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

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]

References

1. France pubmed.ncbi.nlm.nih.gov

[Sorafenib and radiotherapy association for hepatocellular carcinoma]. [2018]

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

Concurrent Sorafenib and Radiotherapy versus Radiotherapy Alone for Locally Advanced Hepatocellular Carcinoma: A Propensity-Matched Analysis. [2022]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Feasibility of sorafenib combined with local radiotherapy in advanced hepatocellular carcinoma. [2022]

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

A phase I, dose-finding study of sorafenib in combination with gemcitabine and radiation therapy in patients with unresectable pancreatic adenocarcinoma: a Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) study. [2022]

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

Phase 1 Trial of Sorafenib and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma. [2022]

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

Prognostic significance of adverse events in patients with hepatocellular carcinoma treated with sorafenib. [2022]

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

Sorafenib continuation or discontinuation in patients with unresectable hepatocellular carcinoma after a complete response. [2018]

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

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

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

SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma. [2022]

10. England pubmed.ncbi.nlm.nih.gov

A rare case of sorafenib-induced severe hyponatremia. [2022]

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

Maintenance of Sorafenib following combined therapy of three-dimensional conformal radiation therapy/intensity-modulated radiation therapy and transcatheter arterial chemoembolization in patients with locally advanced hepatocellular carcinoma: a phase I/II study. [2021]

12. Ireland pubmed.ncbi.nlm.nih.gov

Phase I trial of radiation therapy and sorafenib in unresectable liver metastases. [2018]