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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: hydroxychloroquine

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Hamilton, New Jersey, United States, 08690
      • Cancer Institute of New Jersey At Hamilton
    • Montclair, New Jersey, United States, 07042
      • Mountainside Hospital
    • Morristown, New Jersey, United States, 07962
      • Carol G. Simon Cancer Center at Morristown Memorial Hospital
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
    • New Brunswick, New Jersey, United States, 08903
      • St. Peters University Hospital
    • Summit, New Jersey, United States, 07901
      • Overlook Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: docetaxel; Drug: hydroxychloroquine

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	Time Frame
Time to Disease Progression	10 years
Overall Survival	10 years

Collaborators and Investigators

• Sponsor: University of Medicine and Dentistry of New Jersey
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mark Stein, MD, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: November 5, 2008
• First Submitted That Met QC Criteria: November 5, 2008
• First Posted (Estimated): November 6, 2008

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: stage IV prostate cancer; recurrent prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Docetaxel; Hydroxychloroquine
• Other Study ID Numbers: CDR0000617998; P30CA072720 (U.S. NIH Grant/Contract); CINJ-080805 (Other Identifier: Cancer Institute of New Jersey)