A Phase 2 Study of Pazopanib (GW786034) in Patients With Advanced and Progressive Malignant Pheochromocytoma or Paraganglioma
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
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
True response proportion in patients who receive the study treatment and have advanced malignant pheochromocytomas and paragangliomas
Ninety-five percent confidence intervals for the true response proportion will be calculated according to the approach of Duffy and Santner.
Up to 5 years
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|Metro-Minnesota CCOP||St. Louis Park, Minnesota|
|M D Anderson Cancer Center||Houston, Texas 77030|