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CompletedNCT00459862Updated Feb 24, 2015Results posted

Pazopanib in Treating Patients With Malignant Pleural Mesothelioma

A Phase 2 interventional study of laboratory biomarker analysis and pazopanib hydrochloride in Advanced Malignant Mesothelioma, Localized Malignant Mesothelioma and Recurrent Malignant Mesothelioma, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-02-24.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
34
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Advanced Malignant Mesothelioma
  • Localized Malignant Mesothelioma
  • Recurrent Malignant Mesothelioma
03

In context

Mesothelioma

470 studies on the registry are indexed under Mesothelioma; 75 are open to participants now.

This study's enrollment of 34 is below the median of 40 across 371 interventional studies indexed under Mesothelioma.

Browse Mesothelioma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
34 participants (actual)

Study arms

  • Experimental
    Arm I

    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.

    Other: laboratory biomarker analysis · Drug: pazopanib hydrochloride

Interventions

  • Otherlaboratory biomarker analysis

    Correlative study

  • Drugpazopanib hydrochloride

    Given orally

06

What researchers measure

Primary outcomes

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

    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.

    Time frame: 6 months

Secondary outcomes

  1. Overall Survival

    Time frame: From study enrollment to time of death from any cause or censored at last follow-up, up to 3 years

  2. 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

  3. Determine the Clinical Toxicities of This Drug in This Participant Population.

    The number of participants with a reported Grade 3, Grade 4, and Grade 5 toxicity, regardless of attribution, will be tabulated.

    Time frame: Participants will be evaluated every cycle during treatment

  4. Overall Best Response of Target Lesions to Pazopanib in Patients With MPM Based on the RECIST.

    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.

    Time frame: From study enrollment to the first date of disease progression

  5. Overall Response Rate

    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.

    Time frame: Participants will be evaluated every cycle during treatment, up to 2 years

07

Results

Posted Dec 5, 2013

Participant flow

Thirty-four participants were accrued between May 2007 and October 2008.

Participant flow — Overall Study
MilestoneArm I
Started34
Completed34
Not completed0

Outcome measures

PrimaryProportion of Evaluable Participants Who Are Progression-free at 6 Months Based on the Response Evaluation Criteria for Solid Tumors (RECIST)

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.

Time frame:
6 months
Reported as:
Number · percentage of participants
Proportion of Evaluable Participants Who Are Progression-free at 6 Months Based on the Response Evaluation Criteria for Solid Tumors (RECIST)
percentage of participantsArm I
Proportion of Evaluable Participants Who Are Progression-free at 6 Months Based on the Response Evaluation Criteria for Solid Tumors (RECIST)47.8
SecondaryOverall Survival
Time frame:
From study enrollment to time of death from any cause or censored at last follow-up, up to 3 years
Reported as:
Median · months
Overall Survival
monthsArm I
Overall Survival11.5 (6.2 to 18.2)
SecondaryProgression-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
Reported as:
Median · months
Progression-free Survival Assessed by RECIST
monthsArm I
Progression-free Survival Assessed by RECIST4.2 (2.5 to 5.9)
SecondaryDetermine the Clinical Toxicities of This Drug in This Participant Population.

The number of participants with a reported Grade 3, Grade 4, and Grade 5 toxicity, regardless of attribution, will be tabulated.

Time frame:
Participants will be evaluated every cycle during treatment
Reported as:
Number · participants
Determine the Clinical Toxicities of This Drug in This Participant Population.
participantsArm I
Grade 3 or Higher23
Grade 4 or Higher5
Grade 53
SecondaryOverall Best Response of Target Lesions to Pazopanib in Patients With MPM Based on the RECIST.

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.

Time frame:
From study enrollment to the first date of disease progression
Reported as:
Number · participants
Overall Best Response of Target Lesions to Pazopanib in Patients With MPM Based on the RECIST.
participantsArm I
Partial Response (PR)5
Complete Response (CR)0
SecondaryOverall Response Rate

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.

Time frame:
Participants will be evaluated every cycle during treatment, up to 2 years
Reported as:
Number · percentage of patients
Overall Response Rate
percentage of patientsArm I
Overall Response Rate5.9 (0.7 to 19.7)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm I—13/34 (38.2%)34/34 (100%)
Most frequent serious events
Showing 10 of 34
Most frequent serious events
EventArm I
FatigueGeneral disorders4/34
DyspneaRespiratory, thoracic and mediastinal disorders3/34
NauseaGastrointestinal disorders2/34
VomitingGastrointestinal disorders2/34
Muscle weaknessMusculoskeletal and connective tissue disorders2/34
SyncopeNervous system disorders2/34
Hemoglobin decreasedBlood and lymphatic system disorders1/34
DyspepsiaGastrointestinal disorders1/34
FlatulenceGastrointestinal disorders1/34
Chest painGeneral disorders1/34
Most frequent other events
Showing 10 of 77
Most frequent other events
EventArm I
FatigueGeneral disorders27/34
HypertensionVascular disorders27/34
NauseaGastrointestinal disorders19/34
Alanine aminotransferase increasedInvestigations19/34
Aspartate aminotransferase increasedInvestigations19/34
Hemoglobin decreasedBlood and lymphatic system disorders17/34
Abdominal painGastrointestinal disorders16/34
DiarrheaGastrointestinal disorders15/34
AnorexiaMetabolism and nutrition disorders13/34
ProteinuriaRenal and urinary disorders13/34

Baseline characteristics

Age, Continuous
Age, Continuous(years)Arm I
Median73 (49 to 84)
Sex: Female, Male
Sex: Female, Male(Participants)Arm I
Female6
Male28
Region of Enrollment
Region of Enrollment(participants)Arm I
United States34
08

Study locations

1 site
  • North Central Cancer Treatment Group
    Rochester, Minnesota 55905, United States
09

References and documents

Publications

  • Parikh K, Mandrekar SJ, Allen-Ziegler K, Esplin B, Tan AD, Marchello B, Adjei AA, Molina JR. A Phase II Study of Pazopanib in Patients with Malignant Pleural Mesothelioma: NCCTG N0623 (Alliance). Oncologist. 2020 Jun;25(6):523-531. doi: 10.1634/theoncologist.2019-0574. Epub 2019 Dec 24. PubMed 31872928 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 24, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00459862
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Apr 13, 2007
Start date
Mar 2007
Primary completion
Apr 2009
Completion
May 2013
Results posted
Dec 5, 2013
Last update
Feb 24, 2015

Study contacts

Julian Molina
principal investigator · North Central Cancer Treatment Group
View the source record on ClinicalTrials.gov ↗

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