Clinical Trial: Pazopanib Hydrochloride in Treating Patients With Advanced or Progressive Malignant Pheochromocytoma or Paraganglioma

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase 2 Study of Pazopanib (GW786034) in Patients With Advanced and Progressive Malignant Pheochromocytoma or Paraganglioma

Brief Summary: 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.

Detailed Summary:

PRIMARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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 tiss
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Response Rate (RR) (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.1 [ Time Frame: Up to 5 years ]

Original Primary Outcome: Proportion of patients who have achieved an objective response (partial or complete response [PR or CR]) to pazopanib hydrochloride as defined by RECIST criteria

Current Secondary Outcome:

• 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.

Original Secondary Outcome:

• Proportion of patients who have achieved a CR, PR, or stable disease and who have remained on treatment for at least 6 months
• TTP and PFS of patients treated with pazopanib hydrochloride
• Correlation of the % drop in urinary catecholamines/metanephrines in patients with secretory tumors

Dates:
Date Received: April 21, 2011
Date Started: May 2011
Date Completion:
Last Updated: June 9, 2016
Last Verified: June 2016