Docetaxel and Hydroxychloroquine in Treating Patients With Metastatic Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00786682
• Other study ID #: CDR0000617998
• Secondary ID: P30CA072720CINJ-
• Status: Terminated
• Phase: Phase 2
• Start date: December 2008
• Est. completion date: October 2012

Study information

• Verified date: July 2023
• Source: Rutgers, The State University of New Jersey
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• docetaxel

• hydroxychloroquine

Locations

Country	Name	City	State
United States	Cancer Institute of New Jersey at Hamilton	Hamilton	New Jersey
United States	Mountainside Hospital	Montclair	New Jersey
United States	Carol G. Simon Cancer Center at Morristown Memorial Hospital	Morristown	New Jersey
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	St. Peters University Hospital	New Brunswick	New Jersey
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Overlook Hospital	Summit	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
University of Medicine and Dentistry of New Jersey	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to Disease Progression		10 years
Secondary	Overall Survival		10 years