Prostate Cancer
Conditions
Keywords
recurrent prostate cancer, stage IV prostate cancer, Prostate-Specific Antigen
Brief summary
This phase II trial studies how well hydroxychloroquine works in treating patients with previously treated prostate cancer. Autophagy destroys proteins and other substances in cells and may be used by prostate cancer cells to survive. Hydroxychloroquine, which blocks autophagy, may slow the growth of and possibly kill prostate cancer cells.
Interventions
DRUGhydroxychloroquine
Hydroxychloroquine will be taken at a dose of 200 mg twice per day in the first 27 patients (cohort A). Once cohort A completed, the dose of hydroxychloroquine will then be increased to 600mg per day (200mg three times per day)(cohort B).
Sponsors
Rutgers Cancer Institute of New Jersey
National Cancer Institute (NCI)
Rutgers, The State University of New Jersey
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven stage D0 prostate cancer (i.e., tumor originally diagnosed as being limited to the prostate) or D1 prostate cancer (metastatic to regional lymph nodes) and have a rising PSA value after definitive local therapy. * Must have undergone local treatment via prostatectomy or radiation therapy. * Must have PSA progression after local treatment: 1. PSA values for patients after surgery must be \> 0.2 ng/mL, determined by two measurements, at least 1 month apart and at least 6 months after prostatectomy 2. PSA values for patients after radiation must be ≥ 2.0 ng/ml greater than the nadir achieved after radiation, determined by two measurements at 1 month apart and at least 6 months after the radiation treatment is completed. (Patients who received adjuvant or salvage radiation after prostatectomy must have PSA of \>0.2) 3. The first two PSA values (in 5.1.3a and 5.1.3b), along with a third (study baseline) value must all be rising (i.e., there must be an overall rising trajectory, such that the third value cannot be lower than the first value). * Baseline bone scan and CT abdomen/pelvis demonstrating no metastatic disease. * Age ≥ 18 years * Estimated life expectancy of at least 6 months. * ECOG performance status \< 2. (see Appendix B) * A WBC \> 3500/μl, ANC \>1500/μl, hemoglobin \> 10 g/dl, and platelet count \>100,000/μl are required. * Adequate renal function (serum creatinine \< 1.5 mg/dL or creatinine clearance \> 50 ml/min). * Total bilirubin must be within 1.5X the normal institutional limits. If total bilirubin is outside the normal institutional limits, assess direct bilirubin. The direct bilirubin must be within normal parameters. Transaminases (SGOT and/or SGPT) must be less than 2.5X the institutional upper limit of normal. * Documented ophthalmic exam within the last twelve months demonstrating no evidence of retinopathy. Patients with retinal changes will be considered for enrollment with written clearance from a board certified ophthalmologist. * Must have a serum total testosterone level ≥150 ng/dL at the time of enrollment within 4 weeks prior to randomization. * Must sign informed consent.
Exclusion criteria
* Serious concomitant systemic disorder that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator. * Must be off ADT in the neoadjuvant, adjuvant and/or salvage setting for at least 3 months and have a testosterone level \> 150 ng/dl. * Second primary malignancy except most situ carcinoma (e.g. adequately treated non-melanomatous carcinoma of the skin) or other malignancy treated at least 5 years previously with no evidence of recurrence. * Rheumatoid arthritis or systemic lupus erythematosus treatment. * Psoriasis. * Receiving any disease-modifying anti-rheumatic drug (DMARD). * Active clinically significant infection requiring antibiotics. * G6PD deficiency. * Taking other commercially available medications which may theoretically either stimulate or inhibit autophagy, which are calcitriol and chloroquine. * Taking medications which may lead to interactions with hydroxychloroquine, including penicillamine, telbivudine, botulinum toxin, digoxin, and propafenone. * Must not have 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prostate-specific Antigen (PSA) Response | 6 years | PSA response will be defined as a change in slope of at least 25%, when log (PSA) is plotted vs. time |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect on Peripheral Blood Mononuclear Cell (PBMC) LC3 Expression by the Use of Hydroxychloroquine | 6 years | A change of at least 25% from baseline will be considered to be a significant response |
| Effect on PBMC Autophagic Vesicle Formation by the Use of Hydroxychloroquine | 6 years | — |
| Expression of Beclin-1 in a Population of Patients Having Undergone Local Treatment With Prostatectomy | 6 years | — |
| Feasibility and Safety of Administering Hydroxychloroquine in This Population of Patients. Rate of Adverse Events | 6 years | Rate of adverse events were captured utilizing the CTCAE version3.0. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited through the Rutgers Cancer Institute of New Jersey Oncology Group. The study was open to accrual on 08/05/2008 and closed to accrual to 04/10/2013
Pre-assignment details
We are reporting results on 64 eligible patients. 14 patients were deemed ineligible.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A. Hydroxychloroquine (200mg Bid) Hydroxychloroquine - 400 mg (cohort A)
Hydroxychloroquine will be taken at a dose of 200 mg twice per day in the first 27 patients (cohort A). | 36 |
| Cohort B. Hydroxychloroquine (200mg Tid) Hydroxychloroquine - 600 mg (cohort B)
Once cohort A is completed, the dose of hydroxychloroquine will then be increased to 600mg per day (200mg three times per day)(cohort B). | 28 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Cohort A. Hydroxychloroquine (200mg Bid) | Cohort B. Hydroxychloroquine (200mg Tid) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 31 Participants | 19 Participants | 50 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 9 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 28 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 31 Participants | 24 Participants | 55 Participants |
| Region of Enrollment United States | 36 participants | 28 participants | 64 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 36 Participants | 28 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 36 | 0 / 28 |
| other Total, other adverse events | 20 / 36 | 23 / 28 |
| serious Total, serious adverse events | 1 / 36 | 0 / 28 |
Outcome results
Primary
Prostate-specific Antigen (PSA) Response
PSA response will be defined as a change in slope of at least 25%, when log (PSA) is plotted vs. time
Time frame: 6 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A. Hydroxychloroquine (200mg Bid) | Prostate-specific Antigen (PSA) Response | 48 percentage of participants |
| Cohort B. Hydroxychloroquine (200mg Tid) | Prostate-specific Antigen (PSA) Response | 48 percentage of participants |
p-value: 0.6789t-test, 1 sided
Secondary
Effect on PBMC Autophagic Vesicle Formation by the Use of Hydroxychloroquine
Time frame: 6 years
Population: Data was not collected and the outcome measure was not analyzed.
Secondary
Effect on Peripheral Blood Mononuclear Cell (PBMC) LC3 Expression by the Use of Hydroxychloroquine
A change of at least 25% from baseline will be considered to be a significant response
Time frame: 6 years
Population: Data was not collected and the outcome measure was not analyzed.
Secondary
Expression of Beclin-1 in a Population of Patients Having Undergone Local Treatment With Prostatectomy
Time frame: 6 years
Population: Data was not collected and the outcome measure was not analyzed.
Secondary
Feasibility and Safety of Administering Hydroxychloroquine in This Population of Patients. Rate of Adverse Events
Rate of adverse events were captured utilizing the CTCAE version3.0.
Time frame: 6 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A. Hydroxychloroquine (200mg Bid) | Feasibility and Safety of Administering Hydroxychloroquine in This Population of Patients. Rate of Adverse Events | 30 Participants |
| Cohort B. Hydroxychloroquine (200mg Tid) | Feasibility and Safety of Administering Hydroxychloroquine in This Population of Patients. Rate of Adverse Events | 22 Participants |