Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Pazopanib With or Without Bicalutamide in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Active	18 and over	NCI	PMH-PHL-058 7640, PMH-10036920, PHL-058, NCT00486642

Objectives

Primary

1. Determine the PSA response rate in patients with hormone-refractory prostate cancer treated with pazopanib hydrochloride with vs without bicalutamide.

Secondary

1. Determine objective tumor response in patients with measurable disease treated with these regimens.
2. Determine the median time to progression in patients treated with these regimens.
3. Determine the safety and tolerability of these regimens in these patients.
4. Determine the median duration of PSA response in patients treated with this regimen.
5. Determine the steady state levels of these regimens in these patients.
6. Investigate the correlation between prior exposure to bicalutamide and non-steroidal anti-androgens with response and survival outcomes.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed prostate cancer



• Must have received prior hormonal therapy, including either medical (luteinizing hormone-releasing hormone [LHRH] agonist) or surgical (orchiectomy) castration
  • Castrate level of testosterone (< 50 ng/dL)
  • Patients treated with LHRH agonists must continue or restart this therapy



• Must have radiological documentation of either measurable or non-measurable disease



• Must show documented progression of prostate cancer while on hormonal therapy as indicated by PSA increase
  • Rising PSA is defined as ≤ 2 consecutive rises in PSA taken ≥ 1 week and ≤ 2 months apart



• PSA ≥ 5 ng/mL



• No known brain metastases

Prior/Concurrent Therapy:

• See Disease Characteristics
• Recovered from all prior therapy
• Prior neoadjuvant or adjuvant chemotherapy allowed
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
• At least 4 weeks since prior antiandrogens
• At least 4 weeks since prior surgery
• No prior bicalutamide therapy lasting > 3 months in duration
• Concurrent steroids allowed if no change in steroid dosage within the past 4 weeks
• No other concurrent investigational agents
• No concurrent therapeutic warfarin
  • Concurrent low molecular weight heparin or prophylactic low-dose warfarin allowed
• No concurrent combination antiretroviral therapy for HIV-positive patients

Patient Characteristics:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 3 months
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• INR ≤ 1.2
• Activated PTT ≤ 1.2 times upper limit of normal (ULN)
• Bilirubin normal
• AST and ALT ≤ 1.5 times ULN
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Fertile patients must use effective contraception
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or bicalutamide
• Proteinuria ≤ 1+ on 2 consecutive dipsticks taken ≥ 1 week apart
• QTc < 500 msec
• No significant ECG abnormalities
• No poorly controlled hypertension (systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 90 mm Hg)
• No condition (e.g., gastrointestinal [GI] tract disease resulting in an inability to take oral medication or a requirement for IV alimentation; prior surgical procedures affecting absorption; or active peptic ulcer disease) that impairs the ability to swallow and retain pazopanib hydrochloride tablets
• No serious or nonhealing wound, ulcer, or bone fracture
• No abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28 days
• No cerebrovascular accident within the past 6 months
• No myocardial infarction, cardiac arrhythmia, admission for unstable angina, cardiac angioplasty, or stenting within the past 12 weeks
• No venous thrombosis within the past 12 weeks
• No NYHA class III-IV heart failure
  • Patients with a history of NYHA class II heart failure who are asymptomatic on treatment are eligible
• No concurrent uncontrolled illness, including, but not limited to, ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance

Expected Enrollment

Outcomes

PSA response rate

Time to disease progression
Progression-free survival
Median survival time
Response duration
Survival rate at 1 year
Objective tumor response rate as assessed by RECIST criteria
Stable disease rate as assessed by RECIST criteria
Toxicity

Outline

This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral pazopanib hydrochloride once daily on days 1-28.



• Arm II: Patients receive oral pazopanib hydrochloride once daily on days 1-28. Patients also receive oral bicalutamide once daily on days 8-28 of course 1 and on days 1-28 in all subsequent courses.

Courses in both arms repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood is collected at baseline, on days 8, 15, and 22 of course 1, and on day 1 of courses 2 and 3. Samples are analyzed for pharmacokinetic studies.

After completion of study treatment, patients are followed periodically.

Trial Contact Information

Trial Lead Organizations

Princess Margaret Hospital

Kim Chi, MD, Protocol chair		Ph: 604-877-6000 ext. 2746; 800-663-3333 Email: kchi@bccancer.bc.ca

Canada
British Columbia
	Vancouver
	British Columbia Cancer Agency - Vancouver Cancer Centre
		Kim Chi, MD	Ph:  604-877-6000 ext. 2746 800-663-3333
			Email: kchi@bccancer.bc.ca
Ontario
	Hamilton
	Margaret and Charles Juravinski Cancer Centre
		Som Mukherjee, MD, FRCPC	Ph:  905-387-9711 ext. 64605
	London
	London Regional Cancer Program at London Health Sciences Centre
		Eric Winquist, MD	Ph:  519-685-8500 ext. 58640
	Ottawa
	Ottawa Hospital Regional Cancer Centre - General Campus
		Christina Canil, MD	Ph:  613-737-7700 ext. 70185 888-627-5346
			Email: ccanil@ottawahospital.on.ca
	Toronto
	Princess Margaret Hospital
		Jovana Golubovic	Ph:  416-946-4501 ext. 35

Registry Information
Official Title		A Phase II Study of GW786034 (Pazopanib) With or Without Bicalutamide in Hormone Refractory Prostate Cancer
Trial Start Date		2007-09-06
Trial Completion Date		2009-03-16 (estimated)
Registered in ClinicalTrials.gov		NCT00486642
Date Submitted to PDQ		2007-05-04
Information Last Verified		2009-06-21
NCI Grant/Contract Number		CM62203

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