Autophagy Inhibition + TACE for Liver Cancer

(TAQE Trial)

Overseen By David E Kaplan, MD MSc

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: VA Office of Research and Development

Disqualifiers: QT prolongation, Retinopathy, Pregnancy, others

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve treatment for liver cancer that cannot be surgically removed by combining therapies. It will test whether adding hydroxychloroquine—a drug that blocks a process cancer cells use to survive—to trans-arterial chemoembolization (TACE), which delivers chemotherapy directly to the liver, can kill more cancer cells and enhance the immune system's response. The trial includes two groups: one will receive TACE with hydroxychloroquine, and the other will receive TACE with a placebo. Individuals with liver cancer that meets specific size and imaging criteria, and who have not received previous treatments to the target area, might be suitable candidates. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research has shown that hydroxychloroquine, when combined with trans-arterial chemoembolization (TACE), is generally safe for patients. One study combined hydroxychloroquine with TACE and another drug, and patients tolerated the treatment well, experiencing expected and manageable side effects. Some patients reported nausea and tiredness, common with cancer treatments.

Another review found that hydroxychloroquine, already used for other conditions, demonstrated similar safety results. While side effects can occur, they are usually not serious.

Overall, studies suggest that using hydroxychloroquine with TACE does not cause unexpected safety issues. However, monitoring patient reactions remains important to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for liver cancer, which typically involves treatments like surgery, ablation, or traditional chemotherapy, the investigational treatment in this trial uses hydroxychloroquine as part of a novel approach. Researchers are excited because hydroxychloroquine may inhibit autophagy, a process that cancer cells use to survive, thus potentially making the cancer more vulnerable to treatment. This approach is combined with transarterial chemoembolization (TACE), a targeted method that delivers treatment directly to the tumor, potentially enhancing its effectiveness while sparing healthy tissue. By integrating hydroxychloroquine with TACE, this treatment has the potential to improve outcomes by attacking the cancer on multiple fronts.

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

This trial will compare two treatment approaches for liver cancer. One group of participants will receive trans-arterial chemoembolization (TACE) combined with hydroxychloroquine. Research has shown that TACE cuts off the blood supply to tumors, effectively targeting them. Hydroxychloroquine may block autophagy, a process some cancer cells use to survive by breaking down and reusing their own parts for nutrients. This combination might slow cancer growth and improve tumor response to treatment. Another group in this trial will receive TACE with a placebo instead of hydroxychloroquine. This approach aims to kill more cancer cells and enhance the immune system's ability to fight the cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Terence P Gade, MD PhD

Principal Investigator

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with a specific stage of liver cancer (BCLC B HCC) who are about to undergo TACE therapy. They must have a tumor at least 3 cm wide, be in relatively good health (Childs Pugh Turcotte A/B7, Performance Status 0), and agree to follow the study rules. People can't join if they're pregnant or breastfeeding, have had previous treatments on the target lesion, suffer from certain eye conditions or heart issues, or have other serious medical problems.

Inclusion Criteria

My liver cancer is at least 3 cm wide and meets specific imaging criteria.

I am 18 or older with a diagnosis of intermediate-stage liver cancer and referred for a specific liver cancer treatment.

My liver functions well enough for treatment, and I can care for myself.

Exclusion Criteria

A serum or urine pregnancy test will be performed in women of child-bearing potential at screening

QT prolongation on ECG

Retinopathy on ophthalmologic examination

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intra-arterial hydroxychloroquine with transarterial embolization followed by oral hydroxychloroquine for 6 weeks

6 weeks

1 visit (in-person) for embolization, daily oral medication

Follow-up

Participants are monitored for safety and effectiveness after treatment, including tumor biopsies and serum sampling

6 months

Follow-up visits at 3-4 weeks and 5-6 weeks post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Hydroxychloroquine
• Lipiodol
• Placebo
• TACE

Trial Overview

The study tests whether adding Hydroxychloroquine—an autophagy inhibitor—to standard TACE treatment improves outcomes by killing more cancer cells and boosting anti-tumor immunity compared to TACE alone. Some patients will receive Lipiodol with Hydroxychloroquine while others get Lipiodol with a placebo.

How Is the Trial Designed?

Group I: Transarterial Embolization with Hydroxychloroquine Experimental Treatment 2 Interventions

Intra-arterial hydroxychloroquine in Lipiodol + transarterial embolization followed by oral hydroxychloroquine

Group II: Transarterial Embolization without Hydroxychloquine Placebo Group 2 Interventions

Intra-arterial Lipiodol + transarterial embolization followed by oral placebo

Hydroxychloroquine is already approved in United States, European Union for the following indications:

Approved in United States as Plaquenil for:

• Malaria
• Rheumatoid Arthritis
• Systemic Lupus Erythematosus

Approved in European Union as Plaquenil for:

• Malaria
• Rheumatoid Arthritis
• Systemic Lupus Erythematosus

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

A 71-year-old woman experienced retinal toxicity after taking hydroxychloroquine for 5 years, highlighting the risk of ocular side effects, particularly toxic maculopathy, associated with this medication.

The only effective treatment for hydroxychloroquine toxicity is to discontinue the drug, but the toxic effects may continue to progress due to the slow clearance of the medication, emphasizing the importance of regular eye examinations before and during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal toxicity secondary to Plaquenil therapy. Hanna, B., Holdeman, NR., Tang, RA., et al.[2016]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04873895

Study Details | NCT04873895 | TACE Plus Axitinib and ...

Subjects with liver-dominant colorectal cancer metastases failing at least one line of systemic therapy will receive 2 weeks of axitinib 5mg twice daily (BID) ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12248922/

Efficacy of Transarterial Chemoembolization Combined ...

The results showed that the combination helped delay cancer progression and improve tumor response, especially in patients with hepatitis B-related liver ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10744753/

Efficacy of Transarterial Chemoembolization (TACE) for ...

TACE can be used to treat patients with early-stage HCC who are unsuitable for ablation or surgery. If patients are well selected, TACE may be an alternative ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05842174

Targeting Ischemia-Induced Autophagy Dependence in ...

Trans-arterial chemoembolization (TACE) is the most commonly used therapy for patients with unresectable hepatocellular carcinoma (HCC). TACE is a minimally ...

5.

dovepress.com

dovepress.com/postoperative-adjuvant-transarterial-chemoembolization-plus-tyrosine-k-peer-reviewed-fulltext-article-JHC

Efficacy of adjuvant transarterial chemoembolization | JHC

Conclusion: TACE plus TKI treatment can reduce the incidence of early recurrence with tolerable adverse events in HCC patients at high risk of ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10613419/

Efficacy and Safety of Transarterial Chemoembolization ...

This study aimed to assess the treatment response, survival outcomes, and safety of a novel transarterial chemoembolization (TACE) technique ...

7.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-03204

Transarterial Chemoembolization with Axitinib and ...

This phase IB trial tests the safety and side effects of transarterial chemoembolization (TACE) in combination with axitinib and hydroxychloroquine (HCQ) in ...

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0720048X20301558

Multicentre prospective study of drug-eluting bead ...

In randomised studies, drug-eluting bead transarterial chemoembolisation (DEB-TACE) for the treatment of hepatocellular carcinoma (HCC) has not achieved better ...

9.

tandfonline.com

tandfonline.com/doi/full/10.4161/mco.29911

Chloroquine and hydroxychloroquine for cancer therapy

In particular, the safety and efficacy of CQ are being tested: (1) in subjects with advanced or metastatic breast carcinoma resistant to anthracycline-based ...

10.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10401037/

Safety and efficacy of transarterial chemoembolization ...

TACE combined with TKI and camrelizumab was safe and effective in treating advanced HCC. Triple therapy may benefit patients with large tumor burden and portal ...