Hydroxychloroquine before prostate removal for resectable localized prostate cancer

A Randomized, Placebo Controlled Proof of Principle (Window of Opportunity) Study of Hydroxychloroquine (HCQ) in Prostate Cancer Patients Undergoing Radical Prostatectomy

This randomized, double-blind study tests whether taking hydroxychloroquine before prostatectomy changes tumor autophagy markers and drug levels in men with resectable localized prostate cancer.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Dartmouth-Hitchcock Medical Center (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Lebanon, New Hampshire)
• Trial ID: NCT06408298 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled window-of-opportunity trial giving oral hydroxychloroquine (or placebo) to men with resectable localized prostate cancer prior to radical prostatectomy. Participants take daily hydroxychloroquine sulfate 400 mg or placebo in the pre- and perioperative period, and prostate tumor and normal tissue are collected at surgery. The study measures autophagy markers (including p62, LC3-II, and NBR1), hydroxychloroquine concentrations in tissue and plasma, and performs tumor genomic analysis to correlate molecular features with response. Safety and tolerability in the surgical setting are monitored closely.

Who should consider this trial

Good fit: Adult men with biopsy-proven adenocarcinoma of the prostate (Gleason ≥6) who have resectable localized disease and a planned radical prostatectomy, adequate blood counts and organ function, and sufficient biopsy tissue for study tests are ideal candidates.

Not a fit: Men with metastatic or unresectable disease, those not undergoing radical prostatectomy, or patients with inadequate biopsy tissue or significant organ dysfunction are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the study could show that short-term hydroxychloroquine alters tumor autophagy and identify tissue biomarkers and drug-level data to guide future therapies.

How similar studies have performed: Other early-phase cancer trials have tested hydroxychloroquine as an autophagy inhibitor with mixed or modest signals and no definitive practice-changing results to date.

Eligibility criteria

Inclusion Criteria:

* All patients must have pathological confirmation of adenocarcinoma of the prostate Gleason score 6 (grade Group 1) or greater.
* Patients must have resectable prostate cancer as defined by the AJCC (American Joint Committee on Cancer) TNM system and have planned radical prostatectomy.
* Patients must have sufficient tissue from the initial diagnostic prostate biopsy, as determined by the study pathologist, to perform the required study analyses without exhausting the tissue required for clinical purposes
* Age \>18 years
* Adequate hematopoietic, hepatic and renal function documented prior to study entry to include: Hb. \> 10g/dL, WBC \> 3500/mm3, ANC \> 1500/mm3 and platelets \> 100,000/mm3; hepatic transaminases (AST or ALT) ≤ 2.0 times the upper limits of normal, total bilirubin ≤ 1.5 times the upper limits of normal, estimated creatinine clearance ≥ 60 mL/min or eGFR \> 60 mL/min/1.73 m2 and normal serum cations (K+/Mg2+/Ca2+)
* All patients must be medically fit candidates for radical prostatectomy.
* A patient with any retinopathy will only be enrolled into the study with the approval of a board-certified ophthalmologist
* All patients must give informed consent indicating they are aware of the investigational nature of this study treatment prior to any study procedures being performed.

Exclusion Criteria:

* Patients may not have received radiation therapy for their prostate cancer.
* Patients may not have received chemotherapy for their prostate cancer.
* Patients with gastrointestinal abnormalities including: inability to take oral medication, requirement for intravenous alimentation, or prior major surgery or diseases which may cause malabsorption (e.g. bowel resection, ischemic bowel, Crohns or Ulcerative colitis)
* A serious uncontrolled medical disorder or active infection which would impair their ability to receive study treatment will be excluded.
* Patients with significant cardiac disease: including uncontrolled high blood pressure, unstable angina, congestive heart failure, myocardial infarction within the previous 3 months, or serious cardiac arrhythmias, including a QT interval corrected for heart rate using the Fridericia formula of ≥ 450 ms, or history of Torsade de pointes will be excluded.
* Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol will be excluded.
* Patients receiving any disease-modifying anti-rheumatic drugs (DMARDs) will be excluded.
* Patients with known or a history of G6PD deficiency will be excluded. Eligible patients will be based on clinician-investigator assessment, that the patient is not at an increased risk for G6PD deficiency (assessment should include information regarding self-reported race/ancestry), OR the patient has a negative screening test for G6PD deficiency.
* Patients taking other commercially available medications which may theoretically either stimulate or inhibit autophagy (calcitriol and chloroquine) will be excluded.
* Patients chronically taking drugs known to cause torsades de pointes will be excluded unless those agents can be discontinued for a period \> 6 times their half-life before study enrollment
* Patients with poorly controlled diabetes mellitus will be excluded.
* Patients with a history of epilepsy will be excluded.
* Patients with a history of porphyria will be excluded

Where this trial is running

Lebanon, New Hampshire

• Dartmouth-Hitchcock Medical Center — Lebanon, New Hampshire, United States (RECRUITING)

Study contacts

• Principal investigator: Lionel Lewis, MB BCh., MD — Dartmouth-Hitchcock Medical Center
• Study coordinator: Bridget M Labrie

Conditions: Resectable Localized Prostate Cancer