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
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.
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.
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 →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.
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Inclusion Criteria:
Histologically or cytologically confirmed malignant pleural mesothelioma:
No symptomatic, untreated, or uncontrolled CNS metastases
Patients with CNS metastases treated with whole brain radiation (WBRT) may be enrolled after completion of WBRT
No condition that impairs ability to swallow and retain study drug tablets including, but not limited to, any of the following:
None of the following concurrent severe and/or uncontrolled medical conditions:
No cardiovascular illness or complication, including any of the following:
NYHA class III-IV heart failure
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 concurrent therapeutic warfarin
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
Correlative study
Given orally
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
Overall Survival
Time frame: From study enrollment to time of death from any cause or censored at last follow-up, up to 3 years
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
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
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
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
Thirty-four participants were accrued between May 2007 and October 2008.
| Milestone | Arm I |
|---|---|
| Started | 34 |
| Completed | 34 |
| Not completed | 0 |
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.
| percentage of participants | Arm I |
|---|---|
| Proportion of Evaluable Participants Who Are Progression-free at 6 Months Based on the Response Evaluation Criteria for Solid Tumors (RECIST) | 47.8 |
| months | Arm I |
|---|---|
| Overall Survival | 11.5 (6.2 to 18.2) |
| months | Arm I |
|---|---|
| Progression-free Survival Assessed by RECIST | 4.2 (2.5 to 5.9) |
The number of participants with a reported Grade 3, Grade 4, and Grade 5 toxicity, regardless of attribution, will be tabulated.
| participants | Arm I |
|---|---|
| Grade 3 or Higher | 23 |
| Grade 4 or Higher | 5 |
| Grade 5 | 3 |
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.
| participants | Arm I |
|---|---|
| Partial Response (PR) | 5 |
| Complete Response (CR) | 0 |
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.
| percentage of patients | Arm I |
|---|---|
| Overall Response Rate | 5.9 (0.7 to 19.7) |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm I | — | 13/34 (38.2%) | 34/34 (100%) |
| Event | Arm I |
|---|---|
| FatigueGeneral disorders | 4/34 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 3/34 |
| NauseaGastrointestinal disorders | 2/34 |
| VomitingGastrointestinal disorders | 2/34 |
| Muscle weaknessMusculoskeletal and connective tissue disorders | 2/34 |
| SyncopeNervous system disorders | 2/34 |
| Hemoglobin decreasedBlood and lymphatic system disorders | 1/34 |
| DyspepsiaGastrointestinal disorders | 1/34 |
| FlatulenceGastrointestinal disorders | 1/34 |
| Chest painGeneral disorders | 1/34 |
| Event | Arm I |
|---|---|
| FatigueGeneral disorders | 27/34 |
| HypertensionVascular disorders | 27/34 |
| NauseaGastrointestinal disorders | 19/34 |
| Alanine aminotransferase increasedInvestigations | 19/34 |
| Aspartate aminotransferase increasedInvestigations | 19/34 |
| Hemoglobin decreasedBlood and lymphatic system disorders | 17/34 |
| Abdominal painGastrointestinal disorders | 16/34 |
| DiarrheaGastrointestinal disorders | 15/34 |
| AnorexiaMetabolism and nutrition disorders | 13/34 |
| ProteinuriaRenal and urinary disorders | 13/34 |
| Age, Continuous(years) | Arm I |
|---|---|
| Median | 73 (49 to 84) |
| Sex: Female, Male(Participants) | Arm I |
|---|---|
| Female | 6 |
| Male | 28 |
| Region of Enrollment(participants) | Arm I |
|---|---|
| United States | 34 |
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