Pazopanib in Treating Patients With Malignant Pleural Mesothelioma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00459862
First received: April 11, 2007
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

This phase II trial is studying the side effects and how well pazopanib works in treating patients with malignant pleural mesothelioma. 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.


Condition Intervention Phase
Advanced Malignant Mesothelioma
Localized Malignant Mesothelioma
Recurrent Malignant Mesothelioma
Other: laboratory biomarker analysis
Drug: pazopanib hydrochloride
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of GW786034 in Patients With Malignant Pleural Mesothelioma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of Evaluable Participants Who Are Progression-free at 6 Months Based on the Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The proportion of patients who are progression-free at 6 months is calculated by dividing the number of evaluable participants who are progression-free at 6 months based on the Response Evaluation Criteria for Solid Tumors (RECIST) by the total number of evaluable participants.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From study enrollment to time of death from any cause or censored at last follow-up, up to 3 years ] [ Designated as safety issue: No ]
  • Progression-free Survival Assessed by RECIST [ Time Frame: From study enrollment to the first date of disease progression or death as a result of any cause, whichever occurs first, up to 3 years ] [ Designated as safety issue: No ]
  • Determine the Clinical Toxicities of This Drug in This Participant Population. [ Time Frame: Participants will be evaluated every cycle during treatment ] [ Designated as safety issue: Yes ]
    The number of participants with a reported Grade 3, Grade 4, and Grade 5 toxicity, regardless of attribution, will be tabulated.

  • Overall Best Response of Target Lesions to Pazopanib in Patients With MPM Based on the RECIST. [ Time Frame: From study enrollment to the first date of disease progression ] [ Designated as safety issue: No ]

    Complete Response (CR): Disappearance of all target lesions.

    Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline LD.



Enrollment: 55
Study Start Date: March 2007
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Other: laboratory biomarker analysis
Correlative study
Drug: pazopanib hydrochloride
Given orally

Detailed Description:

PRIMARY OBJECTIVES:

I. 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.

II. Determine the clinical toxicities of this drug in this patient population.

SECONDARY OBJECTIVES:

I. Determine the objective tumor response status in these patients as measured by the RECIST criteria or the modified RECIST criteria.

II. Determine the response rate in patients treated with this drug. III. Determine the effect of this drug on overall survival and time to progression in these patients.

IV. Assess predictive markers of activity of this drug in these patients. V. Assess serologic markers of target inhibition by this drug in these patients.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • ECOG performance status 0-2
  • Life expectancy >= 12 weeks
  • ANC >=1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • WBC >= 3,000/mm^3
  • 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
  • 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 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 ancillary therapy considered investigational within the past 4 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
  • No more than 1 prior systemic therapy for malignant pleural mesothelioma
  • No major surgery (i.e., laparotomy) or open biopsy within the past 4 weeks

    • Insertion of a vascular access device is not considered major or minor surgery
  • No minor surgery within the past 2 weeks

    • Insertion of a vascular access device is not considered major or minor surgery
  • 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
  • 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 other severe underlying disease that, in the judgment of the investigator, would limit study compliance
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00459862

Locations
United States, Minnesota
North Central Cancer Treatment Group
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Julian Molina North Central Cancer Treatment Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00459862     History of Changes
Other Study ID Numbers: NCI-2009-00656, NCI-2009-00656, CDR0000539269, N0623, N0623, U10CA025224
Study First Received: April 11, 2007
Results First Received: October 7, 2013
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial

ClinicalTrials.gov processed this record on July 28, 2014