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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Prostate Carcinoma

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |