Docetaxel and Hydroxychloroquine in Treating Patients With Metastatic Prostate Cancer

This study has been terminated.
(Lack of improved efficacy compared to historical controls, competing studies)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rutgers, The State University of New Jersey ( University of Medicine and Dentistry New Jersey )
ClinicalTrials.gov Identifier:
NCT00786682
First received: November 5, 2008
Last updated: September 23, 2013
Last verified: September 2013

November 5, 2008
September 23, 2013
December 2008
October 2012   (final data collection date for primary outcome measure)
Tumor Response Rate - Primary Endpoint is a 50% Decline in PSA or Normalization of PSA. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
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%.
  • Tumor response rate [ Designated as safety issue: No ]
  • 50% decline or normalization of PSA levels [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00786682 on ClinicalTrials.gov Archive Site
  • Time to Disease Progression [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • Time to disease progression and overall survival [ Designated as safety issue: No ]
  • Feasibility and safety [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Docetaxel and Hydroxychloroquine in Treating Patients With Metastatic Prostate Cancer
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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Drug: docetaxel
  • Drug: hydroxychloroquine
Experimental: Docetaxel and Hydroxychloroquine

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.

Interventions:
  • Drug: docetaxel
  • Drug: hydroxychloroquine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
11
October 2012
October 2012   (final data collection date for primary outcome measure)

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
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00786682
CDR0000617998, P30CA072720, CINJ-080805
No
Rutgers, The State University of New Jersey ( University of Medicine and Dentistry New Jersey )
University of Medicine and Dentistry New Jersey
National Cancer Institute (NCI)
Principal Investigator: Mark Stein, MD Rutgers Cancer Institute of New Jersey
Rutgers, The State University of New Jersey
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP