Distal Urethral CancerPhase 2NCT00471536
Pazopanib in Treating Patients With Metastatic Urothelial Cancer
A Phase 2 study testing pazopanib hydrochloride in people with Distal Urethral Cancer and Proximal Urethral Cancer, run by National Cancer Institute (NCI) at 9 sites in 3 countries.
Trial summary
This phase II trial is studying the side effects and how well pazopanib works in treating patients with metastatic urothelial cancer. 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Distal Urethral Cancer, Proximal Urethral Cancer, Recurrent Bladder Cancer
- What is being tested?
- pazopanib hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 9 sitesin 3 countries
- Study dates
- Aug 2008to Dec 2013
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed transitional cell cancer of the urothelium or bladder
- Metastatic disease
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan
- No known brain metastases
- ECOG performance status 0-2
- Life expectancy ≥ 12 weeks
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- Platelet count ≥ 100,000/mm^3
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Bilirubin normal
- AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- PT/INR/PTT ≤ 1.2 times ULN
- No proteinuria > 1+ on two consecutive dipsticks measured ≥ 1 week apart
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or other agents used in the study
- No condition that impairs the ability to swallow and retain pazopanib hydrochloride tablets, including any of the following:
- Gastrointestinal tract disease resulting in an inability to take oral medication
- Requirement for IV alimentation
- Prior surgical procedures affecting absorption
- Active peptic ulcer disease
- No uncontrolled illness that would limit compliance with study therapy including, but not limited to, any of the following:
- Ongoing or active infection
- Psychiatric illness or social situations
- No QTc prolongation (defined as a QTc interval ≥ 480 msecs) or other significant ECG abnormalities (e.g., frequent ventricular ectopy, evidence of ongoing myocardial ischemia)
- No other conditions, including any of the following:
- Serious or non-healing wound, ulcer, or bone fracture
- Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- Cerebrovascular accident within the past 6 months
- Myocardial infarction, cardiac arrhythmia, or admission for unstable angina within the past 12 weeks
- Venous thrombosis within the past 12 weeks
- New York Heart Association (NYHA) class III or IV heart failure
- Asymptomatic NYHA class II heart failure on treatment allowed
- No other active second malignancy other than non-melanoma skin cancer
- Patients are not considered to have an active malignancy if they have completed anti-cancer therapy and are considered by their physician to be ≤ 30% risk of relapse
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
- At least 4 weeks since prior radiotherapy
- Prior palliative radiotherapy to metastatic lesions allowed provided there is ≥ 1 measurable and/or evaluable lesion(s) that has not been irradiated
- At least 4 weeks since prior surgery
- One prior chemotherapy regimen for metastatic urothelial or bladder cancer
- More than 12 weeks since prior cardiac angioplasty or stenting
- Prior adjuvant or neoadjuvant therapy allowed
- No prior experimental treatment for metastatic disease
- No other prior or concurrent investigational agents
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent CYP2C9 substrates, including any of the following:
- Anticoagulants (e.g., warfarin [therapeutic doses only])
- Low molecular weight heparin and prophylactic low-dose warfarin (≤ 2 mg daily) allowed
- Oral hypoglycemics (e.g., glipizide, glyburide, tolbutamide, glimepiride, or nateglinide)
- Ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, or methylergonovine)
- Antipsychotics (e.g., pimozide or clozapine)
- Erectile dysfunction agents (e.g., sildenafil, tadalafil, or vardenafil)
- Antiarrhythmics (e.g., bepridil, flecainide, lidocaine, mexiletine, amiodarone, quinidine, or propafenone)
- Immune modulators (e.g., cyclosporine, tacrolimus, or sirolimus)
- Miscellaneous drugs (e.g., theophylline, quetiapine, risperidone, tacrine, or atomoxetine)
- No other concurrent anticancer agents or therapies
- No concurrent medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes
Who cannot join
None listed.
Trial locations and contacts
9 sites in 3 countries.
9 sites in 3 countries
United States7 sites
Johns Hopkins University
Baltimore, Maryland, 21287-8936
Wayne State University
Detroit, Michigan, 48202
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Mayo Clinic
Rochester, Minnesota, 55905
Metro-Minnesota CCOP
Saint Louis Park, Minnesota, 55416
Cox Medical Center
Springfield, Missouri, 65807
Washington University School of Medicine
St Louis, Missouri, 63110
China1 site
Chinese University of Hong Kong-Prince of Wales Hospital
Shatin, Hong Kong, OX1 3UJ
About this study
Official title: A Phase II Safety and Efficacy Study With the VEGF Receptor Tyrosine Kinase Inhibitor GW786034 in Patients With Metastatic Urothelial Cancer
This phase II trial is studying the side effects and how well pazopanib works in treating patients with metastatic urothelial cancer. 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.
Read the detailed description
PRIMARY OBJECTIVES:
- Assess the anti tumor activity and toxicity profile of pazopanib hydrochloride in patients with metastatic urothelial cancer.
SECONDARY OBJECTIVES:
- Evaluate the pharmacokinetics of pazopanib hydrochloride in these patients. II. Evaluate pre- and post-treatment changes in circulating endothelial cells, monocytes and platelets, and angiogenesis-related factors in these patients.
OUTLINE: This is a multicenter study. Patients receive oral pazopanib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection periodically for correlative studies and pharmacological studies. Samples are analyzed for vascular endothelial growth factor (VEGF) and soluble VEGF receptor II concentration via ELISA. Circulating endothelial cells are also measured.
After completion of study treatment, patients are followed for 1 year.
- Conditions
- Distal Urethral Cancer, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter, Recurrent Urethral Cancer, Stage IV Bladder Cancer
- Being tested
- pazopanib hydrochloride
- Medical subject headings
- Urinary Bladder Neoplasms, Urethral Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pazopanib hydrochlorideDrug
Also called GW786034B, Votrient
800 mg Given orally
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Patients receive 800 mg oral pazopanib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: pazopanib hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Tumor Response (Complete [CR] or Partial Response [PR] by Response Evaluation Criteria in Solid Tumors [RECIST])
Tumor response is defined as the total number of eligible patients whose disease has a complete or partial response to GW786034 according to the RECIST criteria. Per RECIST v1.0 criteria:
A Complete Response (CR) requires the disappearance of all target lesions.
A Partial Response (PR) requires >=30% decrease in the sum of the longest diameter of target lesions from baseline measurement.
All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response.
Measured: Participants will be evaluated every 8 weeks during treatment and up to 1 year after completion of treatment.
Secondary outcomes (5)
Adverse Events Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
The maximum grade for each adverse event considered to be at least possibly related to treatment will be recorded. Frequency tables will be constructed.
Measured: Every 4 weeks during treatment (maximum duration was 44 weeks)
Confirmed Tumor Response (CR and PR)
Tumor response is defined as the total number of eligible patients whose disease has a complete or partial response to GW786034 according to the RECIST criteria. A confirmed response is defined as a CR or PR and is documented on 2 consecutive evaluations.
Measured: Documented on 2 consecutive evaluations 8 weeks apart from the start of the treatment until disease progression/recurrence, assessed up to 1 year
Duration of Response
The distribution of response durations will be estimated using the Kaplan-Meier method.
Measured: From the time an objective response is first noted to be either a CR or PR to the date progression is documented, assessed up to 1 year
Time to Disease Progression
The distribution of progression-free survival times will be estimated using the Kaplan-Meier method.
Measured: Every 3 months from registration until progressive disease (PD), assessed up to 2 years after registration
Survival Time
The distribution of survival times will be estimated using the Kaplan-Meier method.
Measured: Time from registration until death due to any cause, assessed every 6 months after PD for up to 2 years after registration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2007 (estimated)
- Study startAug 2008
- Primary completionJul 2010
- Study completionDec 2013
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 Distal Urethral 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ulka Vaishampayan, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00471536
- Sponsor's protocol ID
- NCI-2009-00203
- Other IDs
- NCI-2009-00203, CDR0000543460, MAYO-MC0553, MC0553, 7661, N01CM62205
- Status last verified
- Dec 2013
- First submitted
- 8 May 2007
- Last updated
- 30 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Safety and Efficacy Study With the VEGF Receptor Tyrosine Kinase Inhibitor GW786034 in Patients With Metastatic Urothelial Cancer
- ClinicalTrials.gov ID
- NCT00471536
- Acronym / sponsor ID
- NCI-2009-00203
- Conditions
- Distal Urethral Cancer, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter, Recurrent Urethral Cancer, Stage IV Bladder Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Aug 2008
- Primary completion
- Jul 2010 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 10 May 2007 (estimated)
- Results
- Posted 21 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying the side effects and how well pazopanib works in treating patients with metastatic urothelial cancer. 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.
Detailed description
PRIMARY OBJECTIVES:
- Assess the anti tumor activity and toxicity profile of pazopanib hydrochloride in patients with metastatic urothelial cancer.
SECONDARY OBJECTIVES:
- Evaluate the pharmacokinetics of pazopanib hydrochloride in these patients. II. Evaluate pre- and post-treatment changes in circulating endothelial cells, monocytes and platelets, and angiogenesis-related factors in these patients.
OUTLINE: This is a multicenter study. Patients receive oral pazopanib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection periodically for correlative studies and pharmacological studies. Samples are analyzed for vascular endothelial growth factor (VEGF) and soluble VEGF receptor II concentration via ELISA. Circulating endothelial cells are also measured.
After completion of study treatment, patients are followed for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Drug: pazopanib hydrochloridePatients receive 800 mg oral pazopanib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (59 listed)
- Histologically or cytologically confirmed transitional cell cancer of the urothelium or bladder
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan
- No known brain metastases
- ECOG performance status 0-2
- Life expectancy ≥ 12 weeks
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 |
|---|---|---|
| pazopanib hydrochlorideAlso: GW786034B, Votrient800 mg Given orally | Drug | Treatment (enzyme inhibitor therapy) |
Primary outcome
Best Tumor Response (Complete [CR] or Partial Response [PR] by Response Evaluation Criteria in Solid Tumors [RECIST])
Time frame: Participants will be evaluated every 8 weeks during treatment and up to 1 year after completion of treatment.
Tumor response is defined as the total number of eligible patients whose disease has a complete or partial response to GW786034 according to the RECIST criteria. Per RECIST v1.0 criteria: A Complete Response (CR) requires the disappearance of all target lesions. A Partial Response (PR) requires >=30% decrease in the sum of the longest diameter of target lesions from baseline measurement. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response.
5 secondary outcomes
Adverse Events Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Time frame: Every 4 weeks during treatment (maximum duration was 44 weeks)
Confirmed Tumor Response (CR and PR)
Time frame: Documented on 2 consecutive evaluations 8 weeks apart from the start of the treatment until disease progression/recurrence, assessed up to 1 year
Duration of Response
Time frame: From the time an objective response is first noted to be either a CR or PR to the date progression is documented, assessed up to 1 year
Time to Disease Progression
Time frame: Every 3 months from registration until progressive disease (PD), assessed up to 2 years after registration
Survival Time
Time frame: Time from registration until death due to any cause, assessed every 6 months after PD for up to 2 years after registration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Distal Urethral Cancer
Active, not recruitingPhase 2
Fluorouracil, Leucovorin, Gemcitabine, and Cisplatin in Treating Patients With Metastatic or Unresectable Adenocarcinoma of the Urothelium or Urachal Remnant
Bladder Cancer, Urethral Cancer
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.
Ulka Vaishampayan principal investigator
Mayo Clinic
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing pazopanib hydrochloride in people with Distal Urethral Cancer and Proximal Urethral Cancer, run by National Cancer Institute (NCI) at 9 sites in 3 countries.
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 59 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 30 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, China, South Korea. 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 21 Mar 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?
Best Tumor Response (Complete [CR] or Partial Response [PR] by Response Evaluation Criteria in Solid Tumors [RECIST]) (time frame: Participants will be evaluated every 8 weeks during treatment and up to 1 year after completion of treatment.). 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 30 May 2014.