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

Prostate Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02421575
• Other study ID #: 121102
• Secondary ID: NCI-2014-0221602
• Status: Terminated
• Phase: N/A
• First received: December 10, 2014
• Last updated: February 1, 2017
• Start date: July 2012
• Est. completion date: February 26, 2016

Study information

• Verified date: February 2017
• Source: Rutgers, The State University of New Jersey
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: February 26, 2016
• Est. primary completion date: February 26, 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Carcinoma
• Prostatic Neoplasms

Intervention

Drug:
• Hydroxychloroquine
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey

Sponsors (3)

Lead Sponsor	Collaborator
Rutgers, The State University of New Jersey	National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in markers of autophagy in prostate tumor (Group I)		Baseline to 14 days (time of surgery)
Primary	Levels of markers of autophagy in prostate tumor (Group II)		Up to 1 year
Secondary	Distribution of autophagic activity in prostate cancer tissue		Up to 1 year
Secondary	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
Secondary	Levels of markers of apoptosis in tumor tissue		Up to 1 year
Secondary	Clinical activity, as assessed by PSA levels		Up to 1 year
Secondary	Number of CTCs in blood samples	The number of CTCs in pre- and post-treatment blood samples will be determined.	Up to 1 year