Clinical trial NCT02421575: Hydroxychloroquine in Blocking Autophagy in Patients With Prostate Cancer Undergoing Surgery or Active Surveillance
Official title: Assessment of the Biological Effect of Autophagic Inhibition With Hydroxychloroquine in Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Prostate Carcinoma
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Rutgers Cancer Institute of New Jersey
First posted: 2015-04-20
Enrollment: 4
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in markers of autophagy in prostate tumor (Group I)
timeFrame: Baseline to 14 days (time of surgery)
measure: Levels of markers of autophagy in prostate tumor (Group II)
timeFrame: Up to 1 year
Secondary outcomes:
measure: Distribution of autophagic activity in prostate cancer tissue
timeFrame: Up to 1 year
measure: Autophagic activity, assessed by beclin-1 levels
timeFrame: Up to 1 year
measure: Levels of markers of apoptosis in tumor tissue
timeFrame: Up to 1 year
measure: Clinical activity, as assessed by PSA levels
timeFrame: Up to 1 year
measure: Number of CTCs in blood samples
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Eric Singer, MD
role: PRINCIPAL_INVESTIGATOR
References: