Sorafenib + Hydroxychloroquine for Liver Cancer

Overseen By Sukeshi Patel Arora, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center at San Antonio

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: 2

Duration: 28 days per cycle

64 Participants Needed

Trial Summary

What is the purpose of this trial?

The PI is studying if sorafenib/hydroxychloroquine (HCQ) will have improved efficacy when compared to sorafenib alone and in patients progressing of sorafenib the addition of HCQ would lead to disease stability in patients with advanced hepatocellular cancer (HCC).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on enzyme-inducing anti-epileptic medications or other investigational agents.

What data supports the effectiveness of the drug Sorafenib + Hydroxychloroquine for liver cancer?

Sorafenib, one of the drugs in the combination, has been shown to improve survival in liver cancer patients in several large studies, including the SHARP and Sorafenib Asia-Pacific trials. It is currently the only approved systemic treatment for advanced liver cancer, demonstrating its effectiveness in extending patient survival. ^{1 2 3 4 5}

Is the combination of Sorafenib and Hydroxychloroquine safe for liver cancer treatment?

Sorafenib is generally well tolerated in patients with liver cancer, with common side effects including diarrhea and hand-foot skin reactions. Hydroxychloroquine, used for other conditions like malaria and autoimmune diseases, is also generally considered safe, but can cause side effects such as stomach upset and, rarely, eye problems. Always consult with a healthcare provider for personalized advice. ^{1 3 6 7 8}

What makes the drug Sorafenib combined with Hydroxychloroquine unique for liver cancer treatment?

The combination of Sorafenib and Hydroxychloroquine for liver cancer is unique because Sorafenib is the first and only approved systemic drug for advanced liver cancer, known for its ability to inhibit tumor growth and blood vessel formation, while Hydroxychloroquine is being explored for its potential to enhance the effects of Sorafenib by interfering with cancer cell survival mechanisms. ^{1 3 5 9 10}

Research Team

Sukeshi Patel Arora, MD

Principal Investigator

Cancer Therapy & Research Center University of Texas Health Science Center San Antonio

Eligibility Criteria

This trial is for adults with advanced liver cancer who have either not had systemic treatments or those whose disease progressed after at least 4 weeks on sorafenib. They must be in good physical condition, not candidates for curative treatment, and have a life expectancy over 3 months. Exclusions include allergies to similar drugs as HCQ, certain uncontrolled illnesses, brain metastases, and pregnancy.

Inclusion Criteria

My liver function is moderately to mildly impaired.

I agree to use two forms of birth control if I'm a woman not in menopause or surgically sterile, or a barrier method if I'm a man.

My liver cancer is confirmed and advanced or has spread.

Exclusion Criteria

My psoriasis is under control and monitored by a specialist.

I have brain metastases but no symptoms and haven't taken corticosteroids for a week.

I cannot take pills by mouth due to stomach or intestine problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Cohort 1: HCQ added to SOR dose at progression; Cohort 2: SOR-naïve patients receive SOR, with HCQ added on Cycle 1 Day 15

28 days per cycle

Visits on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Disease Evaluation

Disease evaluation every 2 cycles using imaging techniques

Every 8 weeks

Treatment Details

Interventions

• Hydroxychloroquine
• Sorafenib

Trial Overview The study tests if combining Hydroxychloroquine (HCQ) with Sorafenib improves outcomes in advanced liver cancer compared to Sorafenib alone. It's specifically for patients new to treatment or those whose cancer grew despite prior Sorafenib use.

Participant Groups

Group I: Progress on sorafenib Experimental Treatment 2 Interventions

As second-line treatment, we will add hydroxychloroquine (HCQ) to sorafenib (SOR) dose the patient was tolerating at the time of progression.

Group II: No prior systemic treatment Experimental Treatment 2 Interventions

Sorafenib (SOR)-naïve patients receive SOR 400 mg by PO twice daily on Cycle1/Day1 (C1D1). In clinical practice, dose reduction of SOR is often required. Therefore, on C1D15, the clinician will dose-reduce sorafenib based on toxicity and hydroxychloroquine (HCQ) 400 mg PO daily will be started. C2D1 of each cohort, toxicity of HCQ will be assessed. Dose reductions due to adverse events (AEs) to each agent are allowed for SOR per standard of care and/or HCQ for grade 3+ AE.

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?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Targeted therapy for liver cancer: updated review in 2012. [2012]

2. England pubmed.ncbi.nlm.nih.gov

Platelet count less than SHARP: what does a case series reveal? [2018]

3. France pubmed.ncbi.nlm.nih.gov

Sorafenib: A Review in Hepatocellular Carcinoma. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The antitumor activity of a lactosaminated albumin conjugate of doxorubicin in a chemically induced hepatocellular carcinoma rat model compared to sorafenib. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Safety and anti-tumor activity of sorafenib (Nexavar) in combination with other anti-cancer agents: a review of clinical trials. [2022]

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

Sorafenib in unresectable hepatocellular carcinoma from mild to advanced stage liver cirrhosis. [2022]

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

Sorafenib for the treatment of unresectable hepatocellular carcinoma. [2022]

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

Sorafenib: a review of its use in advanced hepatocellular carcinoma. [2022]

9. Belgium pubmed.ncbi.nlm.nih.gov

[Palliative management of hepatocarcinoma with sorafenib (Nexavar). Results of the SHARP study (sorafenib hepatocarcinoma assessment randomized protocol trial)]. [2018]

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

Multiple colon ulcerations, perforation and death during treatment of malignant melanoma with sorafenib. [2018]