Metastatic Digestive System Neuroendocrine Tumor G1 Clinical Trial
Official title:
Prospective Randomized Phase II Trial of Pazopanib (NSC #737754) 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.
PRIMARY OBJECTIVE: I. For patients with progressive carcinoid tumors, 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 (pazopanib hydrochloride) versus placebo. SECONDARY OBJECTIVES: I. Overall survival (OS) 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 (PFS) as assessed by central radiology review and local radiology review will be compared overall and within treatment arms. IV. Safety and tolerability of treatment with pazopanib/placebo will be evaluated within each treatment arm. V. PFS and other indicators of efficacy will be estimated in patients who crossover to pazopanib from placebo. VI. To determine the turn-around time for timely adjudicated central review. VII. To characterize the nature of discordance between local and central radiology review in assessment of progression. VIII. To characterize the type and rate of progression in carcinoid (at study entry, on-study, and at progression). IX. To develop new methods for modeling carcinoid growth and detecting treatment effects, and to perform simulations that advance new clinical trial designs to apply to future trials of carcinoid therapeutics. X. To assess for differences in quality of life (QOL)-related domains between the two treatment groups (pazopanib versus placebo). XI. To determine if the more brief measures of QOL-related domains provide comparable information to that which is provided by the longer assessments (European Organization for Research and Treatment of Cancer [EORTC], neuroendocrine tumors [NET]21). XII. To provide validation data for the EORTC NET21 module in terms of responsiveness over time and differences across arms. XIII. To determine whether components of the plasma angiome panel that have been shown to be predictive previously (interleukin-6 [IL-6] and vascular endothelial growth factor [VEGF]-D) are predictive of a therapeutic advantage for pazopanib treatment in baseline samples from the patients treated on A021202. XIV. To determine whether other components of the plasma angiome panel tested (not IL-6 and VEGF-D) are predictive of a therapeutic advantage for pazopanib treatment in baseline samples from the patients treated on A021202. XV. To evaluate the changes in the plasma angiome markers after treatment with or without pazopanib over time. EXPLORATORY OBJECTIVES: I. PFS at 6 months will be estimated within each treatment arm. II. 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. 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. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and chest x-ray throughout the trial. Patients may optionally undergo blood sample collection during screening and on study. ARM II: Patients receive placebo PO QD on days 1-28. Cycles 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. Patients undergo ECHO or MUGA during screening. Patients also undergo CT, MRI, and chest x-ray throughout the trial. Patients may optionally undergo blood sample collection during screening and on study. After completion of study treatment, patients are followed up every 3-6 months for 5 years. ;
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