Clinical trial NCT00486642: Pazopanib Hydrochloride With or Without Bicalutamide in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy
Official title: A Phase 2 Study of GW786034 (Pazopanib) With or Without Bicalutamide in Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hormone-Resistant Prostate Cancer
Recurrent Prostate Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-06-14
Enrollment: 23
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: PSA Response Rate
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Objective Tumor Response Rate as Assessed by RECIST Criteria
timeFrame: Time from start of treatment to time criteria are met for disease progression or death from any cause, whichever came first, assessed up to 5 years
measure: Progression-free Survival
timeFrame: From time of treatment initiation to disease progression or death from any cause, whichever came first, assessed up to 5 years
measure: Median Duration of PSA-Response
timeFrame: From time PSA response criteria are met until time PSA progression criteria are met or death from any cause, whichever came first, up to 5 years
measure: Stable Disease Rate as Assessed by RECIST Criteria
timeFrame: Measured from the start of the treatment until the criteria for progression are met or death from any cause, whichever came first, assessed up to 5 years
measure: Time to Disease Progression
timeFrame: Time from start of treatment to time criteria are met for disease progression or death from any cause, whichever came first, assessed up to 5 years
measure: Toxicity
timeFrame: Assessed up to 5 years
Other outcomes:
measure: Median Survival Time
timeFrame: Up to 1 year after completion of treatment
measure: Survival Rate
timeFrame: At 1 year
Locations:
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital and Cancer Center-General Campus
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: University Health Network-Princess Margaret Hospital
name: Kim Chi
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sridhar SS, Joshua AM, Gregg R, Booth CM, Murray N, Golubovic J, Wang L, Harris P, Chi KN. A phase II study of GW786034 (pazopanib) with or without bicalutamide in patients with castration-resistant prostate cancer. Clin Genitourin Cancer. 2015 Apr;13(2):124-9. doi: 10.1016/j.clgc.2014.06.001. Epub 2014 Jun 8.