Clinical trial NCT00471536: Pazopanib in Treating Patients With Metastatic Urothelial Cancer
Official title: A Phase II Safety and Efficacy Study With the VEGF Receptor Tyrosine Kinase Inhibitor GW786034 in Patients With Metastatic Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Transitional Cell Carcinoma of the Bladder
Urethral Cancer Associated With Invasive Bladder Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-05-10
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: PRIMARY OBJECTIVES:

I. Assess the anti tumor activity and toxicity profile of pazopanib hydrochloride in patients with metastatic urothelial cancer.

SECONDARY OBJECTIVES:

I. 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.

Eligibility criteria: Inclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Best Tumor Response (Complete [CR] or Partial Response [PR] by Response Evaluation Criteria in Solid Tumors [RECIST])
timeFrame: Participants will be evaluated every 8 weeks during treatment and up to 1 year after completion of treatment.
Secondary outcomes:
measure: Adverse Events Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
timeFrame: Every 4 weeks during treatment (maximum duration was 44 weeks)
measure: Confirmed Tumor Response (CR and PR)
timeFrame: Documented on 2 consecutive evaluations 8 weeks apart from the start of the treatment until disease progression/recurrence, assessed up to 1 year
measure: Duration of Response
timeFrame: 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
measure: Time to Disease Progression
timeFrame: Every 3 months from registration until progressive disease (PD), assessed up to 2 years after registration
measure: Survival Time
timeFrame: Time from registration until death due to any cause, assessed every 6 months after PD for up to 2 years after registration
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro-Minnesota CCOP
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Springfield
country: United States
facility: Cox Medical Center
state: Missouri
city: Shatin
country: China
facility: Chinese University of Hong Kong-Prince of Wales Hospital
state: Hong Kong
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
Study officials:
affiliation: Mayo Clinic
name: Ulka Vaishampayan
role: PRINCIPAL_INVESTIGATOR
References: