Prostate CancerPhase 2NCT00945477
Pazopanib as Second Line Therapy in Patients With Metastatic Prostate Cancer Refractory to Total Androgen Blockade
A Phase 2 study testing Pazopanib (GW786034) in people with Prostate Cancer, run by Illinois CancerCare, P.C. at 4 sites in United States.
Trial summary
A growing body of literature supports the role of angiogenesis in the development and spread of a variety of human cancers including prostate cancer. Vascular endothelial growth factor (VEGF) expression is low in normal prostate tissue, but markedly increased in tumor tissues, and has a positive association with tumor… Read more about this study
- Who is it for?
- Ages 18 to 85 years, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Pazopanib (GW786034)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2009to Oct 2012
- 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 to 85 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of adenocarcinoma of the prostate histology, currently on total androgen blockage with a bicalutamide.
- Subjects must provide written informed consent prior to administration of pazopanib or the performance of any study-specific procedures or assessments, and must be willing to comply with treatment and follow up. Procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol. Note: It is not necessary that informed consent be obtained within the protocol-specified screening window.
- Received no prior second line hormone therapy or any chemotherapy. No prior bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or metastatic prostate cancer.
- Must have metastatic diagnosis, meaning disease beyond the prostate gland.
- A progressing PSA of ≥ 3, the PSA will be measured in ≥ 14 days.
- KPS of ≥ 70
Show all 21Show fewer
- Age ≥ 18 years old
- Adequate organ system functions:
- Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
- Hemoglobin ≥ 9 g/dL
- Platelets ≥ 100 X 109/L
- International normalized ratio (INR) ≤ 1.2 X upper limit of normal (ULN)
- Partial thromboplastin time (PTT) ≤ 1.2 X ULN
- Total bilirubin ≤ 1.5 X ULN
- AST and ALT ≤ 2.5 X ULN
- Calculated creatinine clearance ≥ 30 mL/min
- Urine Protein to Creatinine Ratio (UPC)2 < 1
- Total serum calcium concentration < 12.0mg/dL
- Subjects may not have had a transfusion within 7 days of screening assessment.
- If UPC ≥ 1, then a 24-hour urine protein must be assessed. Subjects must have a 24-hour urine protein value < 1 g to be eligible.
- Left ventricular ejection fraction (LVEF) ≥ 55% as assessed by echocardiography or multigated acquisition (MUGA) scan. The same modality used at baseline must be applied for subsequent evaluations.
Who cannot join
- Subjects meeting any of the following criteria must not be enrolled in the study:
- History of another malignancy.
- Note: Subjects who have had another malignancy and have been disease-free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
- History or clinical evidence of central nervous system (CNS) metastases.
- Note: Subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:
- Are asymptomatic and,
Show all 37Show fewer
- Have had no evidence of active CNS metastases for ≥ 6 months prior to enrollment and,
- Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC).
- Clinically significant gastrointestinal abnormalities including, but not limited to:
- Malabsorption syndrome,
- Major resection of the stomach or small bowel that could affect the absorption of study drug,
- Active peptic ulcer disease,
- Inflammatory bowel disease,
- Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation,
- History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
- Presence of uncontrolled infection.
- Prolongation of corrected QT interval (QTc) > 480 milliseconds (msecs).
- History of any one or more of the following cardiovascular conditions within the past 12 months:
- Cardiac angioplasty or stenting,
- Myocardial infarction,
- Unstable angina,
- Symptomatic peripheral vascular disease,
- Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).
- History of cerebrovascular accident (CVA) including transient ischemic attack (TIA).
- History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligible.
- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥150mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg].
- Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure must be re-assessed on two occasions that are separated by a minimum of 24 hours. The mean SBP/DBP values from each blood pressure assessment must be < 150/90mmHg in order for a subject to be eligible for the study. See Section 6.3.2 for instruction on blood pressure measurement and obtaining mean blood pressure values.
- Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
- Evidence of active bleeding or bleeding diathesis
- Hemoptysis within 6 weeks of first dose of study drug.
- Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study.
- Prohibited medications within 28 days unless the half-life of the medication is longer than 28 days, will not be permitted.
- Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
- Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors (e.g., bevacizumab, sunitinib, sorafenib, etc), or are mTOR inhibitors (eg. temsirolimus, everolimus, etc).
- Is now undergoing and/or has undergone in the last 4 weeks immediately prior to first dose of study drug, (surgery, tumor embolization, chemotherapy, radiation therapy, immunotherapy, or biological therapy)
- Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Illinois CancerCare
Bloomington, Illinois, 61701
Illinois CancerCare
Ottawa, Illinois, 61350
Illinois CancerCare
Pekin, Illinois, 61554
Illinois Cancer Care
Peoria, Illinois, 61615
About this study
Official title: A Study of Pazopanib as Second Line Therapy in Patients With Metastatic Prostate Cancer Who Have Received Prior Therapy With an LHRH Agonist.
A growing body of literature supports the role of angiogenesis in the development and spread of a variety of human cancers including prostate cancer.
- Vascular endothelial growth factor (VEGF) expression is low in normal prostate tissue, but markedly increased in tumor tissues, and has a positive association with tumor stage and grade
- Plasma VEGF levels are significantly elevated in patients with hormone refractory prostate cancer (HRPC) compared to those patients with localized disease and have been associated with disease progression in other cancer patient population.
- The Cancer and Leukemic Group-B demonstrated that VEGF levels correlate with survival.
Pazopanib is a potent multi-target receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptors.
Read the detailed description
VEGF expression is low in all normal prostate tissue, but markedly increased in tumor tissue, and has a positive association with MVD (micro vessel density) tumor stage, grade, and disease-specific survival in patients with prostate cancer. VEGF is known to be under the influence of HIF-1α, which is also up-regulated in the majority of prostate cancer tissue. It has been shown that complete androgen blockade down-regulates VEGF expression via the HIF-1α pathway with concomitant up-regulation of thrombospondin and induction of endothelial cell apoptosis. The VEGF pathway appears to be the dominant vascular formation pathway in prostate cancer with bFGF having a lesser role.
Pazopanib , a hydrochloride salt, is a small molecule inhibitor of several tyrosine kinases, ie: VEGF 1, 2, 3, c-KIT and platelet-derived growth factor receptors. The broad blockade of the VEGF receptors should interfere with the VEGF/VEGF-receptor pathway, and have an impact on cell growth.
According to the NCCN guidelines , first line therapy for metastatic prostate cancer is considered total androgen blockade, either utilizing orchiectomy and/or LH/RH agonists plus Casodex.
Second line therapy would depend on the patient's response to first line therapy, urgency of a response, and the location of metastatic disease.
Pazopanib has been explored in several settings. It has recently been looked at with Bicalutamide in hormone refractory prostate cancer. The second study was with earlier disease, i.e. D-0 relapse androgen-sensitive patients. The University of Chicago has a study looking at the sub-population of prostate cancer patients that have a "chemical relapse" in which patients are given one shot of Lupron, and if the PSA is adequately suppressed, the patients are randomized between pazopanib and placebo.
- Conditions
- Prostate Cancer
- Being tested
- Pazopanib (GW786034)
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pazopanib (GW786034)Drug
Also called Pazopanib monohydrochloride salt GW786034
Pazopanib 800 mg daily x 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Advanced prostate cancer, treatment, pazopanib | Experimental | Pazopanib Receives: Drug: Pazopanib (GW786034) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate at 12 Weeks
Response rate defined as 50% decrease in the Prostate Specific Antigen (PSA) level at week 12 compared to baseline
Measured: 12 weeks
Secondary outcomes (1)
Number Adverse Events, Grades 1-5 Using NCI-CTCAE v 3.0
Safety was evaluated by documentation of Adverse Events (AEs), by assessment of clinical laboratory findings, and by physicial examination, including measurement of vital signs and weight in all eleven subjects.
Measured: 0-12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2009 (estimated)
- Study startJul 2009
- Primary completionOct 2012
- Study completionOct 2012
Why it stopped: Slow enrollment
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.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Illinois CancerCare, P.C.
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James Knost, Illinois CancerCare, P.C.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00945477
- Sponsor's protocol ID
- ILCC #1
- Status last verified
- Oct 2013
- First submitted
- 22 Jul 2009
- Last updated
- 18 Nov 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Pazopanib as Second Line Therapy in Patients With Metastatic Prostate Cancer Who Have Received Prior Therapy With an LHRH Agonist.
- ClinicalTrials.gov ID
- NCT00945477
- Acronym / sponsor ID
- ILCC #1
- Conditions
- Prostate Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Illinois CancerCare, P.C.University, hospital or other
- Study start
- Jul 2009
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 24 Jul 2009 (estimated)
- Results
- Posted 18 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A growing body of literature supports the role of angiogenesis in the development and spread of a variety of human cancers including prostate cancer.
- Vascular endothelial growth factor (VEGF) expression is low in normal prostate tissue, but markedly increased in tumor tissues, and has a positive association with tumor stage and grade
- Plasma VEGF levels are significantly elevated in patients with hormone refractory prostate cancer (HRPC) compared to those patients with localized disease and have been associated with disease progression in other cancer patient population.
- The Cancer and Leukemic Group-B demonstrated that VEGF levels correlate with survival.
Pazopanib is a potent multi-target receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptors.
Detailed description
VEGF expression is low in all normal prostate tissue, but markedly increased in tumor tissue, and has a positive association with MVD (micro vessel density) tumor stage, grade, and disease-specific survival in patients with prostate cancer. VEGF is known to be under the influence of HIF-1α, which is also up-regulated in the majority of prostate cancer tissue. It has been shown that complete androgen blockade down-regulates VEGF expression via the HIF-1α pathway with concomitant up-regulation of thrombospondin and induction of endothelial cell apoptosis. The VEGF pathway appears to be the dominant vascular formation pathway in prostate cancer with bFGF having a lesser role.
Pazopanib , a hydrochloride salt, is a small molecule inhibitor of several tyrosine kinases, ie: VEGF 1, 2, 3, c-KIT and platelet-derived growth factor receptors. The broad blockade of the VEGF receptors should interfere with the VEGF/VEGF-receptor pathway, and have an impact on cell growth.
According to the NCCN guidelines , first line therapy for metastatic prostate cancer is considered total androgen blockade, either utilizing orchiectomy and/or LH/RH agonists plus Casodex.
Second line therapy would depend on the patient's response to first line therapy, urgency of a response, and the location of metastatic disease.
Pazopanib has been explored in several settings. It has recently been looked at with Bicalutamide in hormone refractory prostate cancer. The second study was with earlier disease, i.e. D-0 relapse androgen-sensitive patients. The University of Chicago has a study looking at the sub-population of prostate cancer patients that have a "chemical relapse" in which patients are given one shot of Lupron, and if the PSA is adequately suppressed, the patients are randomized between pazopanib and placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Advanced prostate cancer, treatment, pazopanib | Experimental | Drug: Pazopanib (GW786034)Pazopanib |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Diagnosis of adenocarcinoma of the prostate histology, currently on total androgen blockage with a bicalutamide.
- Subjects must provide written informed consent prior to administration of pazopanib or the performance of any study-specific procedures or assessments, and must be willing to comply with treatment and follow up. Procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol. Note: It is not necessary that informed consent be obtained within the protocol-specified screening window.
- Received no prior second line hormone therapy or any chemotherapy. No prior bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or metastatic prostate cancer.
- Must have metastatic diagnosis, meaning disease beyond the prostate gland.
- A progressing PSA of ≥ 3, the PSA will be measured in ≥ 14 days.
Key exclusion criteria (37 listed)
- History of another malignancy.
- Note: Subjects who have had another malignancy and have been disease-free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
- History or clinical evidence of central nervous system (CNS) metastases.
- Note: Subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:
- Clinically significant gastrointestinal abnormalities including, but not limited to:
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 |
|---|---|---|
| Pazopanib (GW786034)Also: Pazopanib monohydrochloride salt GW786034Pazopanib 800 mg daily x 12 weeks | Drug | Advanced prostate cancer, treatment, pazopanib |
Primary outcome
Response Rate at 12 Weeks
Time frame: 12 weeks
Response rate defined as 50% decrease in the Prostate Specific Antigen (PSA) level at week 12 compared to baseline
1 secondary outcome
Number Adverse Events, Grades 1-5 Using NCI-CTCAE v 3.0
Time frame: 0-12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Prostate Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Active, not recruitingObservational study
MRI Fusion Biopsy vs. Micro-Ultrasound Guided Biopsy
Prostate Cancer
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Recruiting
Rehabilitation and Sex Therapy to Optimize Recovery After Prostate Cancer Treatment
Prostate Cancer, Urinary Incontinence
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.
The record lists no contact. Use the official record to reach the sponsor.
4 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 Pazopanib (GW786034) in people with Prostate Cancer, run by Illinois CancerCare, P.C. at 4 sites in United States.
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 21 inclusion and 37 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: stopped early, as of the sponsor's last update on 18 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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 18 Nov 2013). 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?
Response Rate at 12 Weeks (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Nov 2013.