Pazopanib Hydrochloride in Treating Patients With Advanced or Progressive Malignant Pheochromocytoma or Paraganglioma
|Extra-Adrenal Paraganglioma Metastatic Adrenal Gland Pheochromocytoma Paraganglioma Recurrent Adrenal Gland Pheochromocytoma||Other: Laboratory Biomarker Analysis Drug: Pazopanib Hydrochloride||Phase 2|
|Study Design:||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|
- Response Rate (RR) (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.1 [ Time Frame: Up to 5 years ]
Response and progression are evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1) Ninety-five percent confidence intervals for the true response proportion was calculated using the exact binomial test.
Complete Response (CR): All of the following must be true:
- Disappearance of all target and non-target lesions.
- Each lymph node must have reduction in short axis to <1.0 cm.
Partial Response (PR):
At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking baseline measures as reference.
Overall Response (OR) was calculated by summing the number of patients with a CR or PR.
- Duration of Tumor Response [ Time Frame: Up to 5 years ]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.
- Overall Survival Time [ Time Frame: The time from registration to death due to any cause, assessed up to 5 years ]Overall survival time is defined as the time from registration to death due to any cause and will be estimated using the Kaplan-Meier method.
- Progression-free Survival Time [ Time Frame: The time from registration to documentation of disease progression or death, whichever occurs first, assessed up to 5 years ]Progression-free survival is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. Progression-free survival time will be estimated using the Kaplan-Meier method.
- Time to Treatment Failure [ Time Frame: Up to 5 years from registration ]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.
|Study Start Date:||May 2011|
|Study Completion Date:||November 2014|
|Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO QD on days 1-28 (days 1-14 of courses 1 and 2). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Pazopanib Hydrochloride
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.
Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28 (days 1-14 of courses 1 and 2). 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01340794
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Metro-Minnesota NCI Community Oncology Research Program|
|Saint Louis Park, Minnesota, United States, 55416|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|China, Hong Kong|
|Chinese University of Hong Kong-Prince of Wales Hospital|
|Shatin, Hong Kong, China, OX1 3UJ|
|National University Hospital Singapore|
|Singapore, Singapore, 119074|
|Principal Investigator:||Keith Bible||Mayo Clinic Cancer Center P2C|