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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00486642
First received: June 13, 2007
Last updated: April 17, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Hormone-Resistant Prostate Cancer Recurrent Prostate Carcinoma Drug: Bicalutamide Other: Laboratory Biomarker Analysis Drug: Pazopanib Hydrochloride Other: Pharmacological Study Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 2 Study of GW786034 (Pazopanib) With or Without Bicalutamide in Hormone Refractory Prostate Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • PSA Response Rate [ Time Frame: Up to 12 weeks ]
    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).


Secondary Outcome Measures:
  • Objective Tumor Response Rate as Assessed by RECIST Criteria [ Time Frame: 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 ]
    RECIST PR defined as - At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  • Progression-free Survival [ Time Frame: From time of treatment initiation to disease progression or death from any cause, whichever came first, assessed up to 5 years ]

    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


  • Median Duration of PSA-Response [ Time Frame: 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 ]

    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.


  • Stable Disease Rate as Assessed by RECIST Criteria [ Time Frame: 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 ]
    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.

  • Time to Disease Progression [ Time Frame: 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 ]
    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.

  • Toxicity [ Time Frame: Assessed up to 5 years ]
    Patients who came off treatment due to toxicity.


Other Outcome Measures:
  • Median Survival Time [ Time Frame: Up to 1 year after completion of treatment ]
    Calculated by Kaplan and Meier

  • Survival Rate [ Time Frame: At 1 year ]
    Calculated by Kaplan and Meier.


Enrollment: 23
Study Start Date: September 2007
Study Completion Date: September 2015
Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (pazopanib hydrochloride)

Patients receive pazopanib hydrochloride PO QD on days 1-28.

Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Pazopanib Hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient
Other: Pharmacological Study
Correlative studies
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.
Drug: Bicalutamide
Given PO
Other Names:
  • Casodex
  • Cosudex
  • ICI 176,334
  • ICI 176334
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Pazopanib Hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient
Other: Pharmacological Study
Correlative studies

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00486642

Locations
Canada, British Columbia
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 5P9
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Ottawa Hospital and Cancer Center-General Campus
Ottawa, Ontario, Canada, K1H 8L6
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Kim Chi University Health Network-Princess Margaret Hospital
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00486642     History of Changes
Other Study ID Numbers: NCI-2009-00200
NCI-2009-00200 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PMH-PHL-058
PMH-10036920
CDR0000549528
PHL-058 ( Other Identifier: University Health Network-Princess Margaret Hospital )
7640 ( Other Identifier: CTEP )
N01CM00032 ( US NIH Grant/Contract Award Number )
N01CM62203 ( US NIH Grant/Contract Award Number )
Study First Received: June 13, 2007
Results First Received: October 14, 2015
Last Updated: April 17, 2017

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Hormones
Bicalutamide
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Androgen Antagonists
Hormone Antagonists
Antineoplastic Agents

ClinicalTrials.gov processed this record on June 23, 2017