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

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.

Study Type: Interventional

Study Design: Treatment, Open Label

Study Primary Completion Date: October 2011

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.

Intervention(s) in this Clinical Trial

• Drug: docetaxel
• Drug: hydroxychloroquine

Primary Measures

• Tumor response rate
  • Safety Issue?: No
• 50% decline or normalization of PSA levels
  • Safety Issue?: No

Secondary Measures

• Time to disease progression and overall survival
  • Safety Issue?: No
• Feasibility and safety
  • Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Cancer Institute of New Jersey

Overall Clinical Trial Officials and Contacts

Robert S. DiPaola, MD Principal Investigator Cancer Institute of New Jersey  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00786682

Study ID Number: CDR0000617998

ClinicalTrials.gov Identifier: NCT00786682

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database