Clinical trial NCT00786682: Docetaxel and Hydroxychloroquine in Treating Patients With Metastatic Prostate Cancer
Official title: A Phase II Study of Docetaxel and Modulation of Autophagy With Hydroxychloroquine for Metastatic Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: stage IV prostate cancer
recurrent prostate cancer
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-11-06
Enrollment: 11
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Tumor Response Rate - Primary Endpoint is a 50% Decline in PSA or Normalization of PSA.
timeFrame: 4 years
Secondary outcomes:
measure: Time to Disease Progression
timeFrame: 10 years
measure: Overall Survival
timeFrame: 10 years
Other outcomes:
Locations:
city: Hamilton
country: United States
facility: Cancer Institute of New Jersey at Hamilton
state: New Jersey
city: Montclair
country: United States
facility: Mountainside Hospital
state: New Jersey
city: Morristown
country: United States
facility: Carol G. Simon Cancer Center at Morristown Memorial Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: New Brunswick
country: United States
facility: St. Peters University Hospital
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Mark Stein, MD
role: PRINCIPAL_INVESTIGATOR
References: