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

Recurrent Prostate Carcinoma Clinical Trial

Official title:

A Phase 2 Study of GW786034 (Pazopanib) With or Without Bicalutamide in Hormone Refractory Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00486642
• Other study ID #: NCI-2009-00200
• Secondary ID: NCI-2009-00200PM
• Status: Active, not recruiting
• Phase: Phase 2
• First received: June 13, 2007
• Last updated: August 3, 2015
• Start date: September 2007

Study information

• Verified date: July 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This randomized 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. 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 hydrochloride together with bicalutamide may be an effective treatment for prostate cancer.

Description:

PRIMARY OBJECTIVES:

I. To determine the therapeutic activity of GW786034 (pazopanib hydrochloride) with and without bicalutamide in the treatment of hormone-refractory prostate cancer using prostate specific antigen (PSA)-response rate.

SECONDARY OBJECTIVES:

I. To estimate objective tumor response in patients with measurable disease. II. To estimate the median time to progression. III. To investigate the safety and tolerability of GW786034 with and without bicalutamide.

IV. To estimate the median duration of PSA-response. V. To determine the steady state levels of GW786034 with and without bicalutamide.

VI. To investigate the correlation between prior exposure to bicalutamide and non-steroidal anti-androgens with response and survival outcomes.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28.

ARM II: Patients receive pazopanib hydrochloride PO QD on days 1-28. Patients also receive bicalutamide PO QD 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.

After completion of study treatment, patients are followed up every 4 weeks for 12 weeks.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 23
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%

• Life expectancy > 3 months

• White blood cell (WBC) >= 3,000/mm^3

• Absolute neutrophil count (ANC) >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• International normalized ratio (INR) =< 1.2

• Activated partial thromboplastin time (PTT) =< 1.2 times upper limit of normal (ULN)

• Bilirubin normal

• Aspartate aminotransferase (AST) and alanine aminotransferase (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 < 480 msec

• No significant electrocardiogram (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 intravenous (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, gastrointestinal (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 New York Heart Association (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

• 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 human immunodeficiency virus (HIV)-positive patients

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hormone-Resistant Prostate Cancer
• Prostatic Neoplasms
• Recurrent Prostate Carcinoma

Intervention

Drug:
• Bicalutamide
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Pazopanib Hydrochloride
Given PO

Other:
• Pharmacological Study
Correlative studies

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PSA response rate		Up to 12 weeks	No
Secondary	Median survival time	Calculated by Kaplan and Meier	Up to 1 year after completion of treatment	No
Secondary	Objective tumor response rate as assessed by RECIST criteria		Every 12 weeks during treatment and every 4 weeks for up to 12 weeks after completion of treatment	No
Secondary	Progression-free survival		Time from start of treatment to time criteria are met for disease progression, assessed up to 12 weeks	No
Secondary	Response duration	Calculated by Kaplan and Meier.	From the time measurement criteria are first met for complete response (CR) or partial response (PR) until the first date that recurrent disease is objectively documented, assessed up to 12 weeks	No
Secondary	Stable disease rate as assessed by RECIST criteria		Measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, assessed up to 12 weeks	No
Secondary	Survival rate	Calculated by Kaplan and Meier.	At 1 year	No
Secondary	Time to disease progression	Progression is defined as either PSA progression, objective disease progression (Response Evaluation Criteria in Solid Tumors [RECIST] criteria) or cancer-related symptomatic progression and each will be separately analyzed.	Time from start of treatment to time criteria are met for disease progression, assessed up to 12 weeks	No
Secondary	Toxicity		During treatment and up to 12 weeks after completion of study treatment	Yes