Hydroxychloroquine in Blocking Autophagy in Patients With Prostate Cancer Undergoing Surgery or Active Surveillance

Rutgers The State University of New Jersey

Status and phase: Terminated; Early Phase 1

Conditions: Prostate Carcinoma

Treatments: Drug: Hydroxychloroquine; Other: Laboratory Biomarker Analysis

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02421575

NCI-2014-02216 (Registry Identifier)

0220110278

P30CA072720 (U.S. NIH Grant/Contract)

121102 (Other Identifier)

Details and patient eligibility

About

This phase 0 trial studies hydroxychloroquine in blocking autophagy in patients with prostate cancer who are undergoing surgery or active surveillance. Autophagy is a process in which cells break down some parts of themselves to stay alive during times of stress, such as starvation. This may allow cancer cells to survive damage from chemotherapy. Hydroxychloroquine may block this process from happening.

Full description

PRIMARY OBJECTIVES:

I. To determine the effect of different doses of hydroxychloroquine on markers of autophagy in prostate tumor.

SECONDARY OBJECTIVES:

I. To determine the distribution of autophagic activity within prostate cancer tissue.

II. To determine the utility of beclin-1 as a marker of autophagic activity. III. To assess markers of apoptosis in tumor tissue. IV. To perform deep-sequencing on prostate tissue obtained at the time of surgery.

V. To assess prostate-specific antigen (PSA) as a biochemical endpoint of clinical activity.

VI. To determine the number of circulating tumor cells (CTCs) in pre- and post-treatment blood samples.

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP I (PLANNING PROSTATECTOMY): Patients in Group I are randomized to 1 of 2 arms.

ARM I: Patients receive hydroxychloroquine orally (PO) once daily (QD) for 14 days and then undergo prostatectomy.

ARM II: Patients receive a higher dose of hydroxychloroquine PO thrice daily (TID) for 14 days and then undergo prostatectomy.

GROUP II (ACTIVE SURVEILLANCE): Patients receive hydroxychloroquine PO QD. Treatment continues until the beginning of local therapy or for up to 1 year.

Enrollment: 4 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed written informed consent
• Have abnormal digital rectal examination, or abnormal prostate specific antigen (> 4.0 ng/ml), or obstructing prostate, or biopsy proven prostate cancer
• Scheduled for prostate surgery, i.e. transurethral resection of the prostate (TURP) or prostatectomy
• Planned to be treated by active surveillance

Exclusion criteria

• Patients on treatment for rheumatoid arthritis or systemic lupus erythematosus
• Patients with psoriasis
• Patients receiving any disease-modifying anti-rheumatic drug (DMARD)
• Active clinically significant infection requiring antibiotics
• Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Patients taking other commercially available medications which may theoretically either stimulate or inhibit autophagy, which are calcitriol and chloroquine
• Patients taking medications which may lead to interactions with hydroxychloroquine, including penicillamine, telbivudine, botulinum toxin, digoxin, and propafenone
• Patients must not have prior visual field changes from prior 4-aminoquinoline compound use
• Must not be taking hydroxychloroquine for treatment or prophylaxis of malaria
• History of hypersensitivity to 4-aminoquinoline compound

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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4 participants in 3 patient groups

Group I, Arm I (lower dose hydroxychloroquine)

Experimental group

Description:

Patients receive hydroxychloroquine PO QD for 14 days and then undergo prostatectomy.

Treatment:

Other: Laboratory Biomarker Analysis

Drug: Hydroxychloroquine

Group I, Arm II (higher dose hydroxychloroquine)

Experimental group

Description:

Patients receive hydroxychloroquine PO TID for 14 days and then undergo prostatectomy.

Treatment:

Other: Laboratory Biomarker Analysis

Drug: Hydroxychloroquine

Group II (mid-dose hydroxychloroquine)

Experimental group

Description:

Patients receive hydroxychloroquine PO QD. Treatment continues until the beginning of local therapy or for up to 1 year.

Treatment:

Other: Laboratory Biomarker Analysis

Drug: Hydroxychloroquine