Pazopanib in Treating Patients With Malignant Pleural Mesothelioma

Phase 2

Completed

Conditions: Advanced Malignant Mesothelioma
Recurrent Malignant Mesothelioma
Localized Malignant Mesothelioma

Interventions: Other: laboratory biomarker analysis
Drug: pazopanib hydrochloride

Registration Number: NCT00459862

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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.

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.

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

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 34

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	pazopanib hydrochloride	Patients receive 800 mg 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.
Arm I	laboratory biomarker analysis	Patients receive 800 mg 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.

Primary Outcome Measures

Name	Time	Method
Proportion of Evaluable Participants Who Are Progression-free at 6 Months Based on the Response Evaluation Criteria for Solid Tumors (RECIST)	6 months	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

Name	Time	Method
Progression-free Survival Assessed by RECIST	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
Determine the Clinical Toxicities of This Drug in This Participant Population.	Participants will be evaluated every cycle during treatment	The number of participants with a reported Grade 3, Grade 4, and Grade 5 toxicity, regardless of attribution, will be tabulated.
Overall Response Rate	Participants will be evaluated every cycle during treatment, up to 2 years	To evaluate the confirmed response rate of pazopanib in patients with MPM based on the RECIST criteria for MPM. Responses are confirmed by repeat assessments that are be performed no less than 4 weeks after the criteria for response are first met. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.
Overall Survival	From study enrollment to time of death from any cause or censored at last follow-up, up to 3 years
Overall Best Response of Target Lesions to Pazopanib in Patients With MPM Based on the RECIST.	From study enrollment to the first date of disease progression	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.