Hormone-Resistant Prostate CancerPhase 2NCT00486642
Pazopanib Hydrochloride With or Without Bicalutamide in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy
A Phase 2 study testing Bicalutamide, Laboratory Biomarker Analysis and Pazopanib Hydrochloride in people with Hormone-Resistant Prostate Cancer and Recurrent Prostate Carcinoma, run by National Cancer Institute (NCI) at 6 sites in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Hormone-Resistant Prostate Cancer, Recurrent Prostate Carcinoma
- What is being tested?
- Bicalutamide, Laboratory Biomarker Analysis and Pazopanib Hydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 6 sitesCanada
- Study dates
- Sep 2007to Sep 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 46Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Canada6 sites
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, K7L 5P9
London Regional Cancer Program
London, Ontario, N6A 4L6
Ottawa Hospital and Cancer Center-General Campus
Ottawa, Ontario, K1H 8L6
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Being tested
- Bicalutamide, Laboratory Biomarker Analysis, Pazopanib Hydrochloride, Pharmacological Study
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BicalutamideDrug
Also called Casodex, Cosudex, ICI 176,334, ICI 176334
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Pazopanib HydrochlorideDrug
Also called GW786034B, Votrient
Given PO
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm A (pazopanib hydrochloride) | Experimental | Patients receive pazopanib hydrochloride PO QD on days 1-28.
. Receives: Other: Laboratory Biomarker Analysis; Drug: Pazopanib Hydrochloride; Other: Pharmacological Study |
| Arm B (pazopanib hydrochloride, bicalutamide) | Experimental | 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. Receives: Drug: Bicalutamide; Other: Laboratory Biomarker Analysis; Drug: Pazopanib Hydrochloride; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 12 weeks
Secondary outcomes (6)
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.
Measured: 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
Measured: 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.
Measured: 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: 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.
Measured: 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.
Measured: Assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2007 (estimated)
- Study startSep 2007
- Primary completionAug 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hormone-Resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kim Chi, Principal investigator, University Health Network-Princess Margaret Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00486642
- Sponsor's protocol ID
- NCI-2009-00200
- Other IDs
- NCI-2009-00200, PMH-PHL-058, PMH-10036920, CDR0000549528, PHL-058, 7640, N01CM00032, N01CM62203
- Status last verified
- Apr 2017
- First submitted
- 13 Jun 2007
- Last updated
- 24 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
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.
PubMed 24993934
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of GW786034 (Pazopanib) With or Without Bicalutamide in Hormone Refractory Prostate Cancer
- ClinicalTrials.gov ID
- NCT00486642
- Acronym / sponsor ID
- NCI-2009-00200
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Sep 2007
- Primary completion
- Aug 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 14 Jun 2007 (estimated)
- Results
- Posted 24 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (pazopanib hydrochloride) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Pazopanib Hydrochloride, Other: Pharmacological StudyPatients receive pazopanib hydrochloride PO QD on days 1-28. . |
| Arm B (pazopanib hydrochloride, bicalutamide) | Experimental | Drug: Bicalutamide, Other: Laboratory Biomarker Analysis, Drug: Pazopanib Hydrochloride, Other: Pharmacological StudyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (46 listed)
- 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
- 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
- PSA >= 5 ng/mL
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BicalutamideAlso: Casodex, Cosudex, ICI 176,334, ICI 176334Given PO | Drug | Arm B (pazopanib hydrochloride, bicalutamide) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm A (pazopanib hydrochloride), Arm B (pazopanib hydrochloride, bicalutamide) |
| Pazopanib HydrochlorideAlso: GW786034B, VotrientGiven PO | Drug | Arm A (pazopanib hydrochloride), Arm B (pazopanib hydrochloride, bicalutamide) |
| Pharmacological StudyCorrelative studies | Other | Arm A (pazopanib hydrochloride), Arm B (pazopanib hydrochloride, bicalutamide) |
Primary outcome
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).
6 secondary outcomes
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
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
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
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
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
Toxicity
Time frame: Assessed up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24993934Sridhar 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kim Chi principal investigator
University Health Network-Princess Margaret Hospital
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bicalutamide, Laboratory Biomarker Analysis and Pazopanib Hydrochloride in people with Hormone-Resistant Prostate Cancer and Recurrent Prostate Carcinoma, run by National Cancer Institute (NCI) at 6 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 46 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PSA Response Rate (time frame: Up to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00486642, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2017.