Sorafenib +/− Radiation Therapy for Liver Cancer

No longer recruiting at 53 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of sorafenib tosylate, both alone and with a specialized type of radiation therapy, in treating liver cancer. The researchers aim to determine if the combination of the drug and radiation therapy is more effective at stopping tumor growth than the drug alone. Participants should have liver cancer that cannot be treated with surgery or other standard methods and should not have received specific prior treatments like sorafenib for an extended period. The trial seeks to determine if the combination treatment can better target and shrink liver tumors while minimizing damage to surrounding healthy tissue. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that both treatments in this trial have undergone prior safety testing. Sorafenib, a drug approved for other uses, is generally well-tolerated, though some patients have reported side effects such as diarrhea and tiredness.

For stereotactic body radiation therapy (SBRT), studies have demonstrated its safety for liver cancer. One study found it effectively controlled tumors with few serious side effects, though some patients experienced mild fatigue.

Overall, both sorafenib and SBRT have shown a history of safety in previous studies, providing a strong basis for their use in treating liver cancer in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine Sorafenib, a targeted cancer drug, with or without radiation therapy, offering a potentially more effective approach to liver cancer treatment. Sorafenib works by blocking tumor cell growth and blood vessel formation, a different mechanism compared to traditional chemotherapy, which generally attacks all rapidly dividing cells. The experimental arm includes stereotactic body radiation therapy (SBRT) before Sorafenib, which may enhance the drug's effectiveness by precisely targeting and shrinking tumors before drug treatment. This combination could offer better outcomes for patients than existing treatments alone, like chemotherapy or Sorafenib solo.

What evidence suggests that this trial's treatments could be effective for liver cancer?

Research has shown that sorafenib tosylate, which participants in this trial may receive, can inhibit liver cancer growth by blocking certain enzymes essential for cancer cell proliferation. Another treatment option in this trial is stereotactic body radiation therapy (SBRT). Studies have found SBRT to be highly effective for liver cancer patients, particularly those ineligible for surgery. SBRT has successfully controlled liver cancer for up to 5 years, achieving a 95% success rate without severe side effects. This trial will test the combination of SBRT followed by sorafenib to determine if it enhances the ability to kill cancer cells. Together, these treatments aim to provide a more robust approach to managing liver cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Laura Dawson

Principal Investigator

Radiation Therapy Oncology Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12460054

Stereotactic body radiotherapy with CyberKnife for liver ... The incidence of radiation-induced liver disease was 4.3%–15.3%. Stereotactic body radiotherapy using CK appears to be an effective and well- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7340168/

Long term outcomes of Stereotactic Body Radiation Therapy ... SBRT confers high local control and long-term survival in a substantial proportion of HCC patients unsuitable for, or refractory to standard local/regional ...

3. redjournal.org redjournal.org/article/S0360-3016(23)07777-5/fulltext

Stereotactic Body Radiation Therapy for Hepatocellular ... This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2405630824001551

Long-term outcomes of more than a decade treating ... SBRT resulted in a 5-year LC of 95% in the treatment of primary liver cancer (HCC). •. No SBRT related ≥ grade 3 toxicity was reported. •. Treatment outcomes of ...

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2512-x

Clinical outcomes and prognostic factors of cyberknife ... Cyberknife SBRT appears to be an effective non-invasive treatment for local unresectable HCC with low risk of severe toxicity.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2405630824001691

Stereotactic body radiation therapy in primary liver tumor To assess its efficacy and safety, we reviewed all patients treated by SBRT for a hepatocellular carcinoma (HCC) over a six-year period. Methods and materials.

7. redjournal.org redjournal.org/article/S0360-3016(24)03562-4/fulltext

Final Results of a Multicenter Prospective Study ... A multicenter prospective study of stereotactic body radiation therapy for previously untreated solitary primary hepatocellular carcinoma.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9956001/

Stereotactic Body Radiotherapy for Hepatocellular ... Stereotactic body radiotherapy (SBRT), a type of external beam radiotherapy, yields local control of hepatocellular carcinoma (HCC) at rates as high as 90%.

9. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/rg.220084

Imaging Features in the Liver after Stereotactic Body ... A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: safety and efficacy. Cancer 2020;126(2):363–372.