Docetaxel and Hydroxychloroquine in Treating Patients With Metastatic Prostate Cancer

• Sponsor: University of Medicine and Dentistry of New Jersey (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00786682
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 11
• Locations: 7
• Arm: 1
• Duration (Months): 46
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: docetaxel; Drug: hydroxychloroquine	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Docetaxel and Modulation of Autophagy With Hydroxychloroquine for Metastatic Hormone Refractory Prostate Cancer
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Time to Disease Progression [10 years]

2. Overall Survival [10 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Institute of New Jersey at Hamilton	Hamilton	New Jersey	United States	08690
2	Mountainside Hospital	Montclair	New Jersey	United States	07042
3	Carol G. Simon Cancer Center at Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
4	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
5	St. Peters University Hospital	New Brunswick	New Jersey	United States	08903
6	Overlook Hospital	Summit	New Jersey	United States	07901
7	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111

Sponsors and Collaborators

• University of Medicine and Dentistry of New Jersey
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Mark Stein, MD, Rutgers Cancer Institute of New Jersey

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Medicine and Dentistry of New Jersey
• ClinicalTrials.gov Identifier: NCT00786682
• Other Study ID Numbers: CDR0000617998; P30CA072720; CINJ-080805
• First Posted: Nov 6, 2008
• Last Update Posted: Nov 25, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by University of Medicine and Dentistry of New Jersey: stage IV prostate cancer; recurrent prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Hydroxychloroquine; Docetaxel

Study Results

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.

Arm/Group Title	Docetaxel and Hydroxychloroquine
Arm/Group Description	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.
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Docetaxel and Hydroxychloroquine
Arm/Group Description	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.
Overall Participants	11
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 45.5%
>=65 years	6 54.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.7 (6.0)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	11 100%
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Tumor Response Rate - Primary Endpoint is a 50% Decline in PSA or Normalization of PSA.
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Docetaxel and Hydroxychloroquine
Arm/Group Description	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.
Measure Participants	0

2. Secondary Outcome

Title	Time to Disease Progression
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

Study was terminated prematurely and insufficient data was collected to assess this outcome measure.

Arm/Group Title	Docetaxel and Hydroxychloroquine
Arm/Group Description	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.
Measure Participants	0

3. Secondary Outcome

Title	Overall Survival
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

Study was terminated prematurely and insufficient data was collected to assess this outcome measure.

Arm/Group Title	Docetaxel and Hydroxychloroquine
Arm/Group Description	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.
Measure Participants	0

Adverse Events

Time Frame	3 years
Arm/Group Title	Docetaxel and Hydroxychloroquine
Arm/Group Description	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.
All Cause Mortality
	Docetaxel and Hydroxychloroquine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Docetaxel and Hydroxychloroquine
	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)
Blood and lymphatic system disorders
Hemorrhage, GU - Bladder	1/11 (9.1%)	1
Infections and infestations
Infection - Other (Specify, __)	2/11 (18.2%)	2
Nervous system disorders
Neuropathy: sensory	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Docetaxel and Hydroxychloroquine
	Affected / at Risk (%)	# Events
Total	8/11 (72.7%)
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)	2/11 (18.2%)	7
Hemoglobin	1/11 (9.1%)	1
Hemorrhage, GU - Urinary NOS	1/11 (9.1%)	1
Edema: limb	1/11 (9.1%)	1
Cardiac disorders
Cardiac General - Other (Specify, __)	1/11 (9.1%)	1
Hypertension	1/11 (9.1%)	3
Endocrine disorders
Hot flashes/flushes	1/11 (9.1%)	1
Gastrointestinal disorders
Diarrhea	3/11 (27.3%)	5
Nausea	2/11 (18.2%)	3
Hemorrhoids	1/11 (9.1%)	1
General disorders
Fatigue (asthenia, lethargy, malaise)	4/11 (36.4%)	6
Pain - Back	2/11 (18.2%)	3
Pain - Joint	2/11 (18.2%)	2
Pain - Abdomen NOS	1/11 (9.1%)	1
Pain - Chest wall	1/11 (9.1%)	1
Pain - Chest/thorax NOS	1/11 (9.1%)	1
Pain - Dental/teeth/peridontal	1/11 (9.1%)	1
Pain - Extremity-limb	1/11 (9.1%)	1
Pain - Head/headache	1/11 (9.1%)	1
Pain - Neck	1/11 (9.1%)	1
Pain - Other (Specify, __)	1/11 (9.1%)	1
Infections and infestations
Infection with unknown ANC - Skin (cellulitis)	1/11 (9.1%)	1
Nervous system disorders
Neuropathy: sensory	3/11 (27.3%)	4
Dizziness	1/11 (9.1%)	1
Renal and urinary disorders
Hemorrhage, GU - Bladder	1/11 (9.1%)	1
Urinary frequency/urgency	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/11 (9.1%)	1
Dyspnea (shortness of breath)	1/11 (9.1%)	1
Pulmonary/Upper Respiratory - Other (Specify, __)	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)	3/11 (27.3%)	3
Dermatology/Skin - Other (Specify, __)	1/11 (9.1%)	1
Pruritus/itching	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.