Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Pazopanib in Treating Patients With Malignant Pleural Mesothelioma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Closed 18 and over NCI NCCTG-N0623 N0623, NCT00459862

Objectives

Primary

1. Determine the effect of pazopanib hydrochloride on the proportion of patients with malignant pleural mesothelioma who are progression-free at 6 months based on the RECIST criteria.
2. Determine the clinical toxicities of this drug in this patient population.

Secondary

1. Determine the objective tumor response status in these patients as measured by the RECIST criteria or the modified RECIST criteria.
2. Determine the response rate in patients treated with this drug.
3. Determine the effect of this drug on overall survival and time to progression in these patients.
4. Assess predictive markers of activity of this drug in these patients.
5. Assess serologic markers of target inhibition by this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed malignant pleural mesothelioma
  • Measurable disease
  • No progressive disease inside or outside of any prior radiation field



• No symptomatic, untreated, or uncontrolled CNS metastases
  • Patients with CNS metastases treated with whole brain radiation (WBRT) may be enrolled after completion of WBRT
    • Patients may begin study therapy as early as the next day after completion of WBRT

Prior/Concurrent Therapy:

• See Disease Characteristics
• No more than 1 prior systemic therapy for malignant pleural mesothelioma
• No ancillary therapy considered investigational within the past 4 weeks
• No major surgery (i.e., laparotomy) or open biopsy within the past 4 weeks*
• No minor surgery within the past 2 weeks*
• Prior palliative radiotherapy allowed
  • No prior palliative radiotherapy to the chest except for a maximum of 3 fractions of radiotherapy for superior vena cava syndrome
• No concurrent therapeutic warfarin
  • Low molecular-weight heparin or prophylactic low-dose warfarin allowed
• No other concurrent chemotherapy, immunotherapy, hormonal therapy, or radiotherapy
• No concurrent medications that act through the CYP450 system
• No concurrent combination antiretroviral therapy for HIV-positive patients

 [Note: *Insertion of a vascular access device is not considered major or minor surgery]

Patient Characteristics:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• ANC ≥1,500/mm³
• Platelet count ≥ 100,000/mm³
• WBC ≥ 3,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 50 mL/min
• Proteinuria ≤ 1+ on 2 consecutive dipsticks taken ≥ 1 week apart
• PT/INR/PTT ≤ 1.2 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective nonhormonal contraception
• No uncontrolled infection
• No uncontrolled blood pressure (BP) (defined as systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg in spite of adequate anti-hypertensive therapy)
• No condition that impairs ability to swallow and retain study drug tablets including, but not limited to, 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 other severe underlying disease that, in the judgment of the investigator, would limit study compliance
• No other primary malignancy except for carcinoma in situ of the cervix or nonmelanomatous skin cancer, unless that prior malignancy was diagnosed and definitively treated ≥ 5 years ago with no subsequent evidence of recurrence
  • Patients with a history of low-grade (Gleason score ≤ 6) localized prostate cancer are eligible even if diagnosed within the past 5 years
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or other agents used in the study
• None of the following concurrent severe and/or uncontrolled medical conditions:
  • Serious or nonhealing wound, ulcer, or bone fracture
  • Abdominal fistula, diverticulosis, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • Poorly controlled diabetes
  • Interstitial pneumonia
  • Extensive and symptomatic interstitial fibrosis of the lung
• No cardiovascular illness or complication, including any of the following:
  • Any history of cerebrovascular accident within the past 6 months
  • History of myocardial infarction (prior electrocardiographic evidence of myocardial injury)
  • History of cardiac arrhythmia (prior electrocardiographic evidence of abnormal heart rhythm)
  • Admission for unstable angina
  • Cardiac angioplasty or stenting within the past 12 months
  • NYHA class III-IV heart failure
    • Asymptomatic NYHA class II heart failure allowed
  • QTc prolongation (defined as a QTc interval ≥ 500 msecs) or other significant electrocardiogram abnormalities
  • Venous thrombosis within the past 12 weeks
• No symptomatic, untreated, or uncontrolled seizure disorder
• No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit study compliance
• No significant traumatic injury within the past 4 weeks

Expected Enrollment

A total of 55 patients will be accrued for this study.

Outcomes

Proportion of patients who are progression-free at 6 months

Response to treatment
Overall survival
Progression-free survival
Duration of response
Time to treatment failure
Toxicity
Tumor markers of angiogenesis

Outline

This is a multicenter study.

Patients receive oral pazopanib hydrochloride once daily on days 1-21. Treatment repeats every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.

Blood is collected at baseline and prior to each course of therapy and analyzed for markers of angiogenesis.

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

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Julian Molina, MD, PhD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu
Nicholas Reuter, MD, Protocol co-chair		Ph: 320-229-4907; 877-229-4907 Email: schosp@cloudnet.com

Registry Information
Official Title		Phase II Study of GW786034 in Patients with Malignant Pleural Mesothelioma
Trial Start Date		2007-03-23
Trial Completion Date		2008-09-23 (estimated)
Registered in ClinicalTrials.gov		NCT00459862
Date Submitted to PDQ		2007-03-09
Information Last Verified		2008-12-08
NCI Grant/Contract Number		CA25224

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