Pazopanib Hydrochloride in Treating Patients With Advanced or Progressive Malignant Pheochromocytoma or Paraganglioma
This phase II trial studies 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: 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 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (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 complete response (CR) or partial response (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 ]
- Association between CYP isoforms and the maximum pazopanib hydrochloride plasma level achieved [ Time Frame: Baseline and during the first course of treatment ] [ Designated as safety issue: No ]
- Tumor response associated with plasma pazopanib hydrochloride levels achieved [ Time Frame: Baseline and during the first course of treatment ] [ Designated as safety issue: No ]A two sample Wilcoxon rank sum test will be used.
- Severe toxicities leading to pazopanib hydrochloride dose reductions and the associated maximum pazopanib hydrochloride level achieved [ Time Frame: Baseline and during the first course of treatment ] [ Designated as safety issue: No ]A two sample Wilcoxon rank sum test will be used.
- Changes in urinary catecholamine and metanephrine levels [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Pazopanib hydrochloride-induced changes in urinary catecholamine and/or metanephrine levels and the association with objective tumor response [ Time Frame: Baseline to during the first course of treatment ] [ Designated as safety issue: No ]
- Tumor response and somatic mutational status [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Tumor response and tumor expression levels of HIF-1a, VEGF-R (total and phospho-) assessed via immunohistochemistry [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Tumor microvessel density assessed using MECA-32 immunohistochemical staining [ Time Frame: 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 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: pazopanib hydrochloride
Other Names:Other: laboratory biomarker analysis
I. To assess the anti-tumor activity (in terms of the tumor response rate using the Response Evaluation Criteria in Solid Tumors [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. For patients with secretory tumors, to examine changes in urinary catecholamine and/or metanephrine levels.
II. For patients with secretory tumors, 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.
III. 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 succinate dehydrogenase complex subunit D [SDHD], succinate dehydrogenase complex subunit B [SDHB], ret proto-oncogene [RET], von Hippel-Lindau tumor suppressor [VHL], neurofibromatosis type-1).
IV. To examine associations between tumor response and tumor expression levels of angiogenic and vascular markers including hypoxia inducible factor 1, alpha (HIF-1a), vascular endothelial growth factor receptor (VEGF-R) (total and phospho-) and microvessel density in archival tumor tissue.
IV. To examine whether the extent of tumor response/regression may be correlated with plasma pazopanib (GW786034) concentration achieved after the third cycle (first cycle after run-in cycles) of pazopanib (GW786034) therapy.
OUTLINE: This is a multicenter study.
Patients receive pazopanib hydrochloride orally (PO) once daily (QD) 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 up to 5 years.
|United States, Arizona|
|Mayo Clinic in Arizona||Recruiting|
|Scottsdale, Arizona, United States, 85259|
|Contact: Nina J. Karlin 480-301-8335 Karlin.email@example.com|
|Principal Investigator: Nina J. Karlin|
|United States, Florida|
|Mayo Clinic in Florida||Recruiting|
|Jacksonville, Florida, United States, 32224-9980|
|Contact: Robert C. Smallridge 904-953-2224 firstname.lastname@example.org|
|Principal Investigator: Robert C. Smallridge|
|United States, Maryland|
|Johns Hopkins University||Recruiting|
|Baltimore, Maryland, United States, 21287-8936|
|Contact: Ross C. Donehower 410-955-8838 email@example.com|
|Principal Investigator: Ross C. Donehower|
|United States, Michigan|
|University of Michigan||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Richard J. Auchus 734-774-7764 firstname.lastname@example.org|
|Principal Investigator: Richard J. Auchus|
|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 612-863-8585 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 314-747-0954 email@example.com|
|Principal Investigator: Jeffrey F. Moley|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Camilo Jimenez 713-792-3245 firstname.lastname@example.org|
|Principal Investigator: Camilo Jimenez|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics||Recruiting|
|Madison, Wisconsin, United States, 53792|
|Contact: Anne M. Traynor 608-263-5389 email@example.com|
|Principal Investigator: Anne M. Traynor|
|China, Hong Kong|
|Chinese University of Hong Kong-Prince of Wales Hospital||Recruiting|
|Shatin, Hong Kong, China, OX1 3UJ|
|Contact: Brigette Ma 852-2632-2118 Brigette@clo.cuhk.edu.hk|
|Principal Investigator: Brigette Ma|
|National University Hospital||Recruiting|
|Singapore, Singapore, 119074|
|Contact: Boon C. Goh 65-6772-4621 firstname.lastname@example.org|
|Principal Investigator: Boon C. Goh|
|Principal Investigator:||Keith Bible||Mayo Clinic|