Hydroxychloroquine for Prostate Cancer

Overseen By Director, IIT Office, PhD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Patrick Hensley

Must be taking: Hydroxychloroquine

Must not be taking: Investigational agents

Disqualifiers: Macular degeneration, Cataracts, G-6-PD deficiency, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding Hydroxychloroquine (a medication commonly used to prevent and treat malaria) to the usual treatments for recurrent oligometastatic prostate cancer can slow the disease and delay more taxing treatments. The aim is to prevent cancer progression and improve quality of life by reducing side effects. The trial suits men whose prostate cancer has returned, showing three or fewer small tumors, and who have not taken Hydroxychloroquine in the past six months. Participants will take Hydroxychloroquine tablets twice a day for three months alongside their regular treatment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not clearly specify if you need to stop taking your current medications, but it does exclude those using certain medications that are not compatible with Hydroxychloroquine. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that Hydroxychloroquine is likely to be safe for humans?

Research has shown that Hydroxychloroquine is generally safe for use. Early studies found that it can boost the release of a protein called PAR-4, which helps fight cancer cells, suggesting potential benefits for prostate cancer.

In these studies, Hydroxychloroquine caused few serious side effects, with most participants experiencing only mild issues, if any. This indicates it might be safe for treating prostate cancer, but discussing personal risks with a doctor remains crucial. Hydroxychloroquine is already approved for other uses, such as treating malaria and certain autoimmune diseases, so its safety for those conditions is well-established. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Most treatments for prostate cancer involve hormone therapy, chemotherapy, or radiation, which work by targeting and reducing cancer cell growth through various mechanisms. But hydroxychloroquine, a drug traditionally used to treat malaria and autoimmune diseases, works differently. It interferes with the cancer cells' ability to recycle their own components, a process called autophagy, which they use to survive under stress. Researchers are excited about hydroxychloroquine because it offers a novel way to potentially weaken or kill prostate cancer cells, especially in cases where other treatments might not be as effective. Plus, its well-known safety profile and oral administration make it a convenient option for patients.

What evidence suggests that Hydroxychloroquine might be an effective treatment for recurrent prostate cancer?

Research suggests that Hydroxychloroquine (HCQ), the treatment under study in this trial, might help fight cancer by blocking autophagy, a process cancer cells use to survive. Studies have shown that Hydroxychloroquine, whether used alone or with other treatments, can slow disease progression and improve patients' quality of life. In one study, 84% of patients experienced disease control, meaning the treatment helped prevent their cancer from worsening. Another key benefit is the increase of a protein called PAR-4, which helps stop cancer cells. Overall, Hydroxychloroquine is considered relatively safe with few side effects. ^{3 6 7 8 9}

Who Is on the Research Team?

Patrick J Hensley, MD

Principal Investigator

University of Kentucky

Peng Wang, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

Men with recurrent oligometastatic prostate cancer, who have had surgery or radiation, can join this trial. They should have three or fewer metastatic lesions and no local disease left. Participants must be able to consent, perform daily activities (ECOG 0-2), and pass an eye exam. Those with allergies to similar drugs, severe eye conditions, prior HCQ use within 6 months, brain metastases, or on ADT are excluded.

Inclusion Criteria

Approval by screening eye exam (disqualifying baseline conditions listed below)

I have up to 3 cancer spread sites and no remaining local cancer.

My prostate cancer has come back after treatment.

Exclusion Criteria

I have severe vision problems or changes in my eyesight.

My cancer has spread to my brain or central nervous system.

I can only see out of one eye.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 400 mg of Hydroxychloroquine per day for 3 months, in addition to standard care treatment of either surgical resection or stereotactic radiation

12 weeks

Regular visits as per standard care

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

12 months

4 visits (in-person) at 3, 6, 9, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Hydroxychloroquine

Trial Overview The trial tests if Hydroxychloroquine (400 mg daily for 3 months) can delay prostate cancer progression by increasing PAR-4 levels in patients after standard treatments like surgery or radiation. The goal is to postpone the need for further therapies while maintaining life quality.

How Is the Trial Designed?

Group I: Hydroxychloroquine Experimental Treatment 1 Intervention

Hydroxychloroquine (HCQ) DOSAGE FORM: 200 mg tablet, oral route DOSAGE: 200 mg BID by mouth, for a total daily dose of 400 mg FREQUENCY: HCQ is taken twice daily (morning and night) with food. DURACTION OF HCQ: 90-days

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?

Patrick Hensley

Lead Sponsor

Trials

1

Recruited

20+

Andrew C. James, MD

Lead Sponsor

Trials

1

Recruited

20+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04011410

Hydroxychloroquine to Increase Tumor Suppressor PAR-4 ... Potential benefits of Hydroxychloroquine include delayed disease progression and delayed initiation of ADT, lessening morbidity and increasing quality of life ...

2. 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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5718030/

chloroquine and hydroxychloroquine as anti-cancer agents The therapy was reported to be relatively safe, and the overall response rate was 40%, with an 84% disease control rate [54]. However, this was ...

4. clinicaltrial.be clinicaltrial.be/en/details/447845?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

HCQ in Resectable Localized Prostate Cancer - Clinical Tr... This is randomized, double blind, placebo controlled proof of principle (window of opportunity) study of oral hydroxychloroquine in patients with resectable ...

5. ctv.veeva.com ctv.veeva.com/study/hcq-in-resectable-localized-prostate-cancer

HCQ in Resectable Localized Prostate Cancer This is randomized, double blind, placebo controlled proof of principle (window of opportunity) study of oral hydroxychloroquine in patients ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.233

Hydroxychloroquine effects on tumor suppressor PAR-4 ... Hydroxychloroquine (HCQ) has been identified to be a potent inducer of PAR-4 secretion and downstream tumor inhibition in preclinical models and Phase I trials.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5655212/

Hydroxychloroquine and risk of cancer in patients with primary ... A recent meta-analysis summarized data from 14 studies found that patients with pSS had a pooled relative risk of 1.53 for overall cancer and 13.76 for non- ...

8. nature.com nature.com/articles/s41598-025-04267-y

Hydroxychloroquine modulates the progression of ... In BPH-induced rats, HCQ markedly reduced prostate weight and index, and PSA, testosterone, dihydrotestosterone, pro-inflammatory cytokines (TNF ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.6_suppl.114

A phase I/II study of hydroxychloroquine and suba- ... ADT-free and metastasis-free survival are 14.3 months (95% CI 4.9-23.8) and 15.9 months (95% CI unevaluable) respectively. PK data will be ...