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

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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Prostate Carcinoma; Hormone-Resistant Prostate Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Pazopanib Hydrochloride; Drug: Bicalutamide

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 5P9
      • Cancer Centre of Southeastern Ontario at Kingston General Hospital
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital and Cancer Center-General Campus
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm A (pazopanib hydrochloride); Patients receive pazopanib hydrochloride PO QD on days 1-28. .	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Pazopanib Hydrochloride; Given PO; Other Names: GW786034B; Votrient
EXPERIMENTAL: Arm B (pazopanib hydrochloride, bicalutamide); 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Pazopanib Hydrochloride; Given PO; Other Names: GW786034B; Votrient; Drug: Bicalutamide; Given PO; Other Names: Casodex; Cosudex; ICI 176,334; ICI 176334

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA Response Rate	Prostate-specific antigen (PSA) response rate (defined as a confirmed > / = 50% decline (minimum 5ng/ml) in PSA from baseline maintained for >4 weeks, and without other evidence of disease progression documented at time of confirmatory values).	Up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Tumor Response Rate as Assessed by RECIST Criteria	RECIST PR defined as - At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	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
Progression-free Survival	PFS is defined as the time from treatment initiation to disease progression or death from any cause, whichever came first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	From time of treatment initiation to disease progression or death from any cause, whichever came first, assessed up to 5 years
Median Duration of PSA-Response	Definition of PSA response: >= 50% fall (minimum 5 ng/ml) in PSA from baseline maintained for >4 weeks, and without other evidence of disease progression documented at time of confirmatory values. PSA response duration will commence on the date of the first >=50% decline in PSA. The response duration ends when PSA progression criteria are met with the second increasing PSA value. PSA progression in PSA responders: rise in PSA of 50% (minimum 5ng/ml) above nadir value and confirmed by a second increasing value at least 1 week later.	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
Stable Disease Rate as Assessed by RECIST Criteria	RECIST Stable defined as - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	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
Time to Disease Progression	Earliest date on which disease progression was determined by any of the methods listed: PSA progression, objective disease progression (Response Evaluation Criteria in Solid Tumors [RECIST] criteria) or cancer-related symptomatic progression.	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
Toxicity	Patients who came off treatment due to toxicity.	Assessed up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Survival Time	Calculated by Kaplan and Meier	Up to 1 year after completion of treatment
Survival Rate	Calculated by Kaplan and Meier.	At 1 year

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Kim Chi, University Health Network-Princess Margaret Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (ACTUAL): August 1, 2015
• Study Completion (ACTUAL): September 1, 2015

Study Registration Dates

• First Submitted: June 13, 2007
• First Submitted That Met QC Criteria: June 13, 2007
• First Posted (ESTIMATE): June 14, 2007

Study Record Updates

• Last Update Posted (ACTUAL): May 24, 2017
• Last Update Submitted That Met QC Criteria: April 17, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Androgen Antagonists; Bicalutamide
• Other Study ID Numbers: NCI-2009-00200 (REGISTRY: CTRP (Clinical Trial Reporting Program)); N01CM62203 (U.S. NIH Grant/Contract); N01CM00032 (U.S. NIH Grant/Contract); PMH-PHL-058; PMH-10036920; CDR0000549528; PHL-058 (OTHER: University Health Network-Princess Margaret Hospital); 7640 (OTHER: CTEP)