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

Assessment of the Biological Effect of Autophagic Inhibition With Hydroxychloroquine in Prostate Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Hydroxychloroquine

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I, Arm I (lower dose hydroxychloroquine); Patients receive hydroxychloroquine PO QD for 14 days and then undergo prostatectomy.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Hydroxychloroquine; Given PO; Other Names: HCQ
Experimental: Group I, Arm II (higher dose hydroxychloroquine); Patients receive hydroxychloroquine PO TID for 14 days and then undergo prostatectomy.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Hydroxychloroquine; Given PO; Other Names: HCQ
Experimental: Group II (mid-dose hydroxychloroquine); Patients receive hydroxychloroquine PO QD. Treatment continues until the beginning of local therapy or for up to 1 year.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Hydroxychloroquine; Given PO; Other Names: HCQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in markers of autophagy in prostate tumor (Group I)	Baseline to 14 days (time of surgery)
Levels of markers of autophagy in prostate tumor (Group II)	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of autophagic activity in prostate cancer tissue		Up to 1 year
Autophagic activity, assessed by beclin-1 levels	The utility of beclin-1 as a marker of autophagic activity will be determined.	Up to 1 year
Levels of markers of apoptosis in tumor tissue		Up to 1 year
Clinical activity, as assessed by PSA levels		Up to 1 year
Number of CTCs in blood samples	The number of CTCs in pre- and post-treatment blood samples will be determined.	Up to 1 year

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI); Rutgers Cancer Institute of New Jersey
• Investigators: Principal Investigator: Eric Singer, MD, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): February 26, 2016
• Study Completion (Actual): February 26, 2016

Study Registration Dates

• First Submitted: December 10, 2014
• First Submitted That Met QC Criteria: April 17, 2015
• First Posted (Estimate): April 20, 2015

Study Record Updates

• Last Update Posted (Estimate): February 2, 2017
• Last Update Submitted That Met QC Criteria: February 1, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: 121102 (Other Identifier: Rutgers Cancer Institute of New Jersey); P30CA072720 (U.S. NIH Grant/Contract); NCI-2014-02216 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 0220110278