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

Must not be taking: Anti-epileptics, Investigational agents

Disqualifiers: Uncontrolled brain metastases, Psoriasis, Macular degeneration, 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: 2

Duration: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding hydroxychloroquine (HCQ) to sorafenib benefits individuals with advanced liver cancer (hepatocellular cancer) more than sorafenib alone. Participants will be divided into two groups: one group will begin with sorafenib and add HCQ if their cancer progresses, while the other group will use both drugs from the start. Candidates include those with advanced liver cancer that cannot be treated with surgery or a transplant, particularly if they have undergone liver-related treatments but not systemic ones like sorafenib. The study seeks individuals who can take oral medication and have stable liver function. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that sorafenib is generally well-tolerated by patients with liver cancer. Common side effects include diarrhea and hand-foot skin reactions, which most people can manage. Studies have demonstrated that sorafenib is safe for treating liver cancer, and the FDA has already approved it for this use, adding confidence in its safety.

Hydroxychloroquine (HCQ) is often used for conditions like malaria and autoimmune diseases. Its safety is well-understood, but like any medication, it can have side effects. This trial combines sorafenib with HCQ to see if the results improve. The safety of this combination is under study, but each drug has been safely used in humans before.

The research aims to determine if adding HCQ to sorafenib can help stabilize the disease in patients whose cancer has progressed on sorafenib alone. The trial explores whether adding HCQ can be both effective and safe for people with advanced liver cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of sorafenib and hydroxychloroquine for liver cancer because it may offer a more effective second-line treatment option. Most current treatments for liver cancer, like sorafenib alone, target cancer cells by blocking tumor growth. However, adding hydroxychloroquine targets a different pathway by potentially disrupting the cancer cells' ability to survive and resist treatment. This dual action could lead to improved outcomes for patients who have progressed on sorafenib or have not received any prior systemic treatment.

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

Research has shown that sorafenib, a treatment for advanced liver cancer, extends patient survival to about 9 to 10.7 months on average. It also delays cancer progression for approximately 4.1 to 5.5 months. Although sorafenib alone is somewhat effective, it remains the standard treatment for this cancer. In this trial, one group of participants will receive sorafenib alone, while another group will receive a combination of sorafenib and hydroxychloroquine (HCQ). Studies suggest that adding HCQ to sorafenib might enhance its effectiveness by affecting autophagy, a process where cells recycle parts of themselves. This may help slow cancer growth, indicating that the combined treatment could be more beneficial than using sorafenib alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Sukeshi Patel Arora, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8267639/

Hydroxychloroquine (HCQ) Modulates Autophagy and ... Recent studies have shown the combination of sorafenib and hydroxychloroquine was very effective in treating patients with metastatic liver cancer [45]. Figure ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4699623/

Chloroquine inhibits hepatocellular carcinoma cell growth ... In the present study, we examined the effects of CQ on the growth and viability of liver cancer cells in vitro and in vivo, and revealed that CQ treatment ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0009279723004179

Hydroxychloroquine: Key therapeutic advances and ... Hydroxychloroquine (HCQ) is a promising anticancer agent in both monotherapy and combined therapy. HCQ may be able to fight cancer through autophagy inhibition.

4. anticancerfund.org anticancerfund.org/sites/default/files/2023-06/verbaanderd_et_al._2017_chloroquine_and_hydroxychloroquine_as_anti-cancer_agent.pdf

chloroquine and hydroxychloroquine as anti-cancer agents Furthermore, Sun et al showed that CQ administration is effective in reducing tumour growth in rats with established hepatocarcinoma. In.

5. mdpi.com mdpi.com/2072-6694/13/13/3227/review_report

Hydroxychloroquine (HCQ) Modulates Autophagy and ... Recent studies had shown the combination of sorafenib and hydroxychloroquine was very effective in treating patients with metastatic liver cancer [45].”.

6. withpower.com withpower.com/trial/phase-3-liver-neoplasms-1-2017-4e2e1

Sorafenib + Hydroxychloroquine for Liver Cancer Sorafenib is generally well tolerated in patients with liver cancer, with common side effects including diarrhea and hand-foot skin reactions.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3574194/

The Role of Sorafenib in the Treatment of Advanced ... Five-year survival rates for these patients can range from 89% – 93%. Unfortunately, HCC is often detected too late for surgery to be effective. Other options ...

8. nature.com nature.com/articles/aps20175

New knowledge of the mechanisms of sorafenib resistance ... In addition, the results of the STORM trial suggest that sorafenib cannot prolong the survival of liver cancer patients who have accepted ...

9. jeccr.biomedcentral.com jeccr.biomedcentral.com/articles/10.1186/s13046-021-01968-w

Advances in drug development for hepatocellular carcinoma In 2018, the results of a randomized phase III trial (REFLECT) demonstrated that lenvatinib was noninferior to sorafenib in terms of OS [16].

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4612290/

Long-term outcomes of patients with advanced ... Disease free survival varied across patients (3-43 months, median: 9 months). Three of the 7 patients showed recurrence after sorafenib therapy. Of these, 1 ...