Docetaxel and Hydroxychloroquine in Treating Patients With Metastatic Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hydroxychloroquine may help docetaxel work better and kill more tumor cells. PURPOSE: This phase II trial is studying how well giving docetaxel together with hydroxychloroquine works in treating patients with metastatic prostate cancer.

Detailed Description
-----------------
OBJECTIVES: Primary To assess the antitumor activity, in terms of tumor response rate, of docetaxel in combination with hydroxychloroquine in patients with metastatic, hormone-refractory, chemotherapy-naive prostate cancer. Secondary To measure time to disease progression and overall survival. To determine the feasibility and safety of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive oral hydroxychloroquine twice daily on days 1-21 and docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days (up to 6 courses with docetaxel) in the absence of disease progression or unacceptable toxicity.

Official Title
-----------------
A Phase II Study of Docetaxel and Modulation of Autophagy With Hydroxychloroquine for Metastatic Hormone Refractory Prostate Cancer

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: docetaxel
* Drug: hydroxychloroquine


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed prostate cancer Metastatic disease, as demonstrated by bone scan and/or CT scan of the abdomen/pelvis Must demonstrate disease progression after initial hormone therapy (including bicalutamide and flutamide) No prior chemotherapy allowed No known brain metastases PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy ≥ 6 months ANC > 1,500/μL Hemoglobin > 10 g/dL Platelet count > 100,000/mm^3 Serum creatinine < 2.0 mg/dL or creatinine clearance > 50 mL/min Total bilirubin normal SGOT and/or SGPT < 1.5 times upper limit of normal (ULN) Alkaline phosphatase < 2.5 times ULN Fertile patients must use effective contraception during and for 3 months after completion of study therapy No second primary malignancy except for most in situ carcinomas (e.g., adequately treated nonmelanoma carcinoma of the skin) or other malignancy treated ≥ 5 years ago with no evidence of recurrence No history or symptoms of cardiovascular disease, including any of the following: NYHA class II-IV cardiovacular disease within the past 6 months Coronary artery disease Arrhythmias Conduction defects with risk of cardiovascular instability Uncontrolled hypertension Clinically significant pericardial effusion Congestive heart failure No uncontrolled intercurrent illness including ongoing active infection that would limit compliance with study requirements No rheumatoid arthritis or systemic lupus erythematosus requiring treatment No psoriasis or porphyria No known HIV infection No hypersensitivity to 4-aminoquinoline compounds, including hydroxychloroquine sulfate, chloroquine phosphate, and amodiaquine No retinal or vision changes from prior 4-aminoquinoline compound use No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 No known G-6PDH deficiency Neurotoxicity ≤ grade 1 PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from all prior therapy No prior taxane At least 4 weeks since prior therapy (including surgery and radiotherapy) At least 1 week since prior herbal supplements At least 6 weeks since prior bicalutamide At least 4 weeks since prior flutamide No current hydroxychloroquine for treatment or prophylaxis Prior hydroxychloroquine allowed No other concurrent investigational or commercial agents or therapies, including chemotherapy, immunotherapy, hormonal cancer therapy, radiotherapy, surgery for cancer, or experimental therapy Concurrent luteinizing-hormone releasing-hormone agonists allowed

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel and Hydroxychloroquine<br>Drug: Docetaxel 75 mg/m2 intravenously every 21 days on Day 1 of the treatment cycle Drug: hydroxychloroquine 200 mg twice daily A cycle is defined as an interval of 21 days. | Drug: docetaxel<br> <br> Drug: hydroxychloroquine<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response Rate - Primary Endpoint is a 50% Decline in PSA or Normalization of PSA. | We will use a two-stage optimal Simon's design with a 5% significance level and 80% power to detect an increase in response rate from 50% to 70%. The first stage will enroll 15 patients. If there are 8 or fewer responses among these 15 patients, we will consider the combination therapy to not be worthy of further study, and stop the trial. If we find 9 or more responses, we will proceed to the second stage, and accrual continues for a total of 43 patients. If we see 26 or fewer responses out of 43, then no further investigation of the drug is warranted. If we see 27 or more responses out of 43, then further investigation of the drug will be considered. The expected sample size of the trial is 23.5 with the null response rate of 50%. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression |  | 10 years | 
| Overall Survival |  | 10 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV prostate cancer, recurrent prostate cancer