Official Title: “A Phase II Study of GW786034 (Pazopanib) With or Without Bicalutamide in Hormone Refractory Prostate Cancer”

RATIONALE: Pazopanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body.

Giving pazopanib together with bicalutamide may be an effective treatment for prostate cancer.

PURPOSE: This phase II trial is studying how well giving pazopanib with or without bicalutamide works in treating patients with prostate cancer that did not respond to hormone therapy.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label

Study Primary Completion Date: March 2009

OBJECTIVES:

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

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

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.

Intervention(s) in this Clinical Trial

• Drug: bicalutamide
  • Given orally
• Drug: pazopanib hydrochloride
  • Given orally

Arms, Groups and Cohorts in this Clinical Trial

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

Primary Measures

• PSA response rate
  • Safety Issue?: No

Secondary Measures

• Time to disease progression
  • Safety Issue?: No
• Progression-free survival
  • Safety Issue?: No
• Median survival time
  • Safety Issue?: No
• Response duration
  • Safety Issue?: No
• Survival rate at 1 year
  • Safety Issue?: No
• Objective tumor response rate as assessed by RECIST criteria
  • Safety Issue?: No
• Stable disease rate as assessed by RECIST criteria
  • Safety Issue?: No
• Toxicity
  • Safety Issue?: Yes

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

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

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Princess Margaret Hospital, Canada

Overall Clinical Trial Officials and Contacts

Kim N. Chi, MD Study Chair British Columbia Cancer Agency  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00486642

Study ID Number: CDR0000549528

ClinicalTrials.gov Identifier: NCT00486642

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database