Prostate Cancer
Conditions
Keywords
stage IV prostate cancer, recurrent prostate cancer
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.
Interventions
DRUGdocetaxel
DRUGhydroxychloroquine
Sponsors
National Cancer Institute (NCI)
University of Medicine and Dentistry of New Jersey
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response Rate - Primary Endpoint is a 50% Decline in PSA or Normalization of PSA. | 4 years | 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%. |
Secondary
| Measure | Time frame |
|---|---|
| Time to Disease Progression | 10 years |
| Overall Survival | 10 years |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Cancer Institute of New Jersey (a comprehensive cancer center) and a community hospital in New Jersey, part of the CINJ Oncology Group, from February 2009 through August 2010.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Docetaxel and Hydroxychloroquine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 65.7 years STANDARD_DEVIATION 6 |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 11 |
| other Total, other adverse events | 8 / 11 |
| serious Total, serious adverse events | 3 / 11 |
Outcome results
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%.
Time frame: 4 years
Population: Upon reviewing response data for the first 8 patients, we noted that there were no responses thus far. As per the two-stage optimal Simon's design, we would need 8 responses in 15 patients to proceed to stage 2 but we would not have crossed that threshold. The study was stopped due to lack of improved efficacy compared to historical controls.
Secondary
Overall Survival
Time frame: 10 years
Population: Study was terminated prematurely and insufficient data was collected to assess this outcome measure.
Secondary
Time to Disease Progression
Time frame: 10 years
Population: Study was terminated prematurely and insufficient data was collected to assess this outcome measure.