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

NCT ID: NCT02421575

Last Updated: 2017-02-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2016-02-26

Brief Summary

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.

Detailed 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.

Conditions

Prostate Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group I, Arm I (lower dose hydroxychloroquine)

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

Group Type: EXPERIMENTAL

Hydroxychloroquine

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Group I, Arm II (higher dose hydroxychloroquine)

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

Group Type: EXPERIMENTAL

Hydroxychloroquine

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Group II (mid-dose hydroxychloroquine)

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

Group Type: EXPERIMENTAL

Hydroxychloroquine

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Hydroxychloroquine

Given PO

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

HCQ

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Rutgers Cancer Institute of New Jersey

OTHER

Sponsor Role: collaborator

Rutgers, The State University of New Jersey

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Singer, MD

Role: PRINCIPAL_INVESTIGATOR

Rutgers Cancer Institute of New Jersey

Locations

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Countries

United States

Other Identifiers

NCI-2014-02216

Identifier Type: REGISTRY

Identifier Source: secondary_id

0220110278

Identifier Type: -

Identifier Source: secondary_id

121102

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA072720

Identifier Type: NIH

Identifier Source: secondary_id

View Link

121102

Identifier Type: -

Identifier Source: org_study_id