Pazopanib Hydrochloride in Treating Patients With Advanced or Progressive Malignant Pheochromocytoma or Paraganglioma
This phase II trial is studying how well pazopanib hydrochloride works in treating patients with advanced or progressive malignant pheochromocytoma or paraganglioma. Pazopanib hydrochloride 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.
Drug: pazopanib hydrochloride
Other: diagnostic laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of Pazopanib (GW786034) in Patients With Advanced and Progressive Malignant Pheochromocytoma or Paraganglioma|
- True response proportion in patients who receive the study treatment and have advanced malignant pheochromocytomas and paragangliomas [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Ninety-five percent confidence intervals for the true response proportion will be calculated according to the approach of Duffy and Santner.
- Safety profile of pazopanib hydrochloride [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]All toxicities will be graded using the NCI CTCAE Version 4.0. For each type of adverse event classified as either possibly, probably, or definitely related to study treatment, the proportion of patients experiencing a severe (grade 3 or higher) adverse event will be noted per cycle. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns.
- Duration of tumor response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Defined for all patients whose tumor met the criteria of CR or PR (using the RECIST criteria) as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented.
- Time to treatment failure [ Time Frame: The time from the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 5 years ] [ Designated as safety issue: No ]
- Progression-free survival time [ Time Frame: The time from registration to documentation of disease progression, assessed up to 5 years ] [ Designated as safety issue: No ]
- Overall survival time [ Time Frame: The time from registration to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||May 2011|
|Estimated Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride orally once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo urine and blood sample collection at baseline and periodically during study for correlative studies.
Drug: pazopanib hydrochloride
Other Names:Other: diagnostic laboratory biomarker analysis
I. To assess the anti-tumor activity (in terms of the tumor response rate using the RECIST criteria) of pazopanib (pazopanib hydrochloride) (GW786034) in patients with advanced malignant pheochromocytomas and paragangliomas.
SECONDARY OBJEC TIVES:
I. To assess safety profile of pazopanib. II. To assess duration of tumor response. III. To assess time to treatment failure. IV. To assess progression-free survival time. V. To assess overall survival time.
I. To examine the association between baseline CYP isoforms and the maximum pazopanib plasma level achieved during the first cycle of treatment.
II. To examine whether tumor response is associated with plasma pazopanib levels achieved during the first cycle of treatment or baseline CYP isoforms.
III. To examine whether severe toxicities leading to pazopanib dose reductions are associated maximum pazopanib level achieved during the first cycle of treatment or baseline CYP isoforms.
IV. To examine changes in urinary catecholamine and/or metanephrine levels. V. To examine whether pazopanib-induced changes in urinary catecholamine and/or metanephrine levels during the first cycle of treatment may be associated with objective tumor response.
VI. To examine associations between tumor response and somatic mutational status in archived tumors, or germline mutational status in patient's peripheral blood mononuclear cells, (presence of SDHD, SDHB, RET, VHL, neurofibromatosis type-1).
VII. To examine associations between tumor response and tumor expression levels of HIF-1a, VEGF-R (total and phospho-) and microvessel density.
OUTLINE: This is a multicenter study. Patients are stratified according to prior tyrosine kinase inhibitor (yes vs no). Patients receive pazopanib hydrochloride orally once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo urine and blood sample collection at baseline and periodically during study for correlative studies.
After completion of study therapy, patients are followed up every 3-6 months for a maximum of 3 years.
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Keith C. Bible 507-284-2511 email@example.com|
|Principal Investigator: Keith C. Bible|
|Saint Louis Park, Minnesota, United States, 55416|
|Contact: Patrick J. Flynn 952-993-1516 firstname.lastname@example.org|
|Principal Investigator: Patrick J. Flynn|
|United States, Missouri|
|Washington University School of Medicine||Recruiting|
|Saint Louis, Missouri, United States, 63110|
|Contact: Jeffrey F. Moley 314-747-0064|
|Principal Investigator: Jeffrey F. Moley|
|United States, Texas|
|M D Anderson Cancer Center||Not yet recruiting|
|Houston, Texas, United States, 77030|
|Contact: Camilo Jimenez email@example.com|
|Principal Investigator: Camilo Jimenez|
|Principal Investigator:||Keith Bible||Mayo Clinic|