Clinical trial NCT00509587: Pazopanib in Treating Patients With Recurrent or Metastatic Breast Cancer
Official title: A Phase 2 Study of GW786034 (Pazopanib) in Patients With Recurrent and/or Metastatic Invasive Breast Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-07-31
Enrollment: 21
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 how well giving pazopanib works in treating patients with recurrent or metastatic invasive breast 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 OBJECTIVE:

I. To determine the antitumor activity of pazopanib, in terms of objective response rate (partial and complete response), in patients with recurrent or metastatic invasive breast cancer.

SECONDARY OBJECTIVES:

I. To determine the duration of objective response, rate and duration of stable disease.

II. To determine 6-month progression-free and median and overall survival rates in patients treated with this drug.

III. To document the safety and tolerability of this drug in these patients.

OUTLINE: This is a multicenter, open label study.

Patients receive oral pazopanib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and at 1, 4, and 8 weeks for correlative laboratory studies. Blood samples are evaluated for the following tumor markers by ELISA: VEGF, bFGF, sFLT-1, sTIE-2, sE-Selectin, VCAM-1, PDGF-AA, PDGF-AB and PDGF-BB. TSP-1 in plasma is measured by Accucyte™ competitive immunoassay.

After completion of study treatment, patients are followed every 3 months.

Eligibility criteria: Criteria:

* No prior bevacizumab
* Histologically or cytologically confirmed invasive breast carcinoma (recurrent or metastatic disease)
* Measurable disease, defined as \>= 1 unidimensionally measurable lesion \>= 20 mm by conventional techniques or \>= 10 mm by spiral CT scan
* Patients who may still benefit from hormonal therapy are ineligible (patients with hormone receptor-positive breast cancer should have received appropriate sequential hormonal therapy for metastatic disease until disease progression)
* Patients with HER-2 positive disease who have not yet received trastuzumab (Herceptin®) to maximal benefit are ineligible (patients with disease progression during trastuzumab therapy are eligible)
* No known brain metastases
* ECOG performance status (PS) 0-1 or Karnofsky PS 60-100%
* Life expectancy \> 12 weeks
* Absolute neutrophil count \>= 1,500/mm³
* Platelets \>=100,000/mm³
* Total bilirubin normal (exception made for patients with known Gilbert's disease)
* AST/ALT =\< 2.5 times upper limit of normal (ULN)
* No proteinuria \> +1 on two consecutive dipsticks taken \>= 1 week apart
* PT/INR/PTT =\< 1.2 times ULN
* No allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib or other study agents
* No QTc prolongation (defined as a QTc interval \>= 500 msecs) or other significant ECG abnormalities
* No condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, or active peptic ulcer disease) that would impair ability to swallow and retain study drug
* No poorly controlled hypertension (systolic blood pressure \[BP\] \>= 140 mm Hg or diastolic BP \>= 90 mm Hg) Initiation or adjustment of BP medication is allowed prior to study entry provided that the average of 3 BP readings prior to study entry is \< 140/90 mm Hg
* No serious or non-healing wound, ulcer, or bone fracture
* No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the last 4 weeks
* No cerebrovascular accident within the last 6 months
* No myocardial infarction, cardiac arrhythmia, hospital admission for unstable angina within the last 12 weeks
* No venous thrombosis within the last 12 weeks
* No NYHA class III-IV heart failure Patients with a history of class II heart failure may be considered eligible provided they are asymptomatic on treatment
* No concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would preclude study compliance
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy, or surgery
* No cardiac angioplasty or stenting within the last 12 weeks
* No more than 1 prior chemotherapy regimen for recurrent disease
* No prior surgical procedures affecting absorption
* No CYP2C9 substrates during or for 1-2 weeks after completion of study treatment, including any of the following:

Therapeutic warfarin Low molecular weight heparin or prophylactic low-dose warfarin are allowed

* No CYP2C9 substrates during or for 1-2 weeks after completion of study treatment, including any of the following:

  * Erectile dysfunction agents: sildenafil, tadalafil, or vardenafil
  * Antiarrhythmics: bepridil, flecainide, lidocaine, mexilitine, amiodarone, or quinidine
  * Immune modulators: cyclosporine, tacrolimus, or sirolimus
  * Miscellaneous: theophylline, quetiapine, or risperidone
* No CYP2C9 substrates during or for 1-2 weeks after completion of study treatment, including any of the following:

  * Oral hypoglycemics: glipizide, glyburide, or tolbutamide
  * Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, or methylergonovine
  * Neuroleptics: pimozide
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No other concurrent investigational agents
* No other concurrent anticancer therapy
* WBC \>= 3,000/mm³
* No more than 2 prior palliative systemic chemotherapy regimens for de novo metastatic disease
* Creatinine normal OR creatinine clearance \>= 60 mL/min
* At least 3 months since prior trastuzumab

Primary outcomes:
measure: Number of Participants With Partial and Complete Response.
timeFrame: Up to 3 years
Secondary outcomes:
measure: Duration of Objective Response
timeFrame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years
measure: Duration of Stable Disease
timeFrame: From the start of the treatment until the criteria for progression are met, assessed up to 3 years
measure: Progression-free Survival
timeFrame: 6 months
measure: Overall Survival
timeFrame: Up to 3 years
measure: Adverse Events Graded According to the NCI CTCAE Version 3.0
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre (Ottawa Health Research Institute) Civic Campus
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: University Health Network-Princess Margaret Hospital
name: Natasha Leighl
role: PRINCIPAL_INVESTIGATOR
References: