Prospective Randomized Phase II Trial of Pazopanib (NSC# 737754, IND 75648) Versus Placebo in Patients with Progressive Carcinoid Tumors
This randomized phase II trial studies how well pazopanib hydrochloride works in treating patients with carcinoid tumors that are growing, spreading, or getting worse. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
I. For patients with progressive carcinoid tumors, progression-free survival (progression-free survival [PFS] defined by central review according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) will be compared between patients randomized to treatment with pazopanib versus placebo.
I. Overall survival will be compared between treatment arms. II. Objective response rate, duration of response, and time to treatment failure will be compared between treatment arms. III. Progression free survival as assessed by central radiology review and local radiology review will be compared overall and within treatment arms. IV. PFS at 6 months and 12 months will be estimated within each treatment arm. V. Safety and tolerability of treatment with pazopanib/placebo will be evaluated within each treatment arm.
VI. Biochemical response (for chromogranin A, defined as a decrease of 50% or more in chromogranin A levels from baseline and for 5-hydroxyindoleacetic acid [5-HIAA], defined as a decrease of 50% or more in urinary 5-HIAA levels from baseline) will be compared between treatment arms among patients with elevated baseline levels of chromogranin A (CGA) and 5-HIAA. VII. PFS and other indicators of efficacy will be estimated in patients who crossover to pazopanib from placebo.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: 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.
ARM II: Patients receive placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of progressive disease, patients may cross-over to Arm I.
After completion of study treatment, patients are followed up every 3-6 months for 5 years.