This phase II trial studies how well lenvatinib works in treating patients with pheochromocytoma or paraganglioma that has spread to other places in the body or cannot be removed by surgery. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To determine the anti-tumor activity of lenvatinib (overall response rate; \[ORR\]) in patients with metastatic or advanced unresectable pheochromocytomas and paragangliomas. SECONDARY OBJECTIVES: I. To determine progression-free survival (PFS). II. To determine overall survival (OS). III. To determine duration of tumor response. IV. To determine safety and tolerability of lenvatinib. V. To assess patient reported quality of life using EuroQol Five-Dimensional Five Level Scale Questionnaire (EQ-5D-5L) and Functional Assessment of Cancer Therapy-General (FACT-G). TERTIARY OBJECTIVES: I. For patients with secretory tumors, to examine changes in plasma metanephrine levels and urinary catecholamine and/or metanephrine levels. II. For patients with secretory tumors, to examine whether lenvatinib-induced changes in plasma metanephrines and 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 (presence of SDHD, SDHB, RET, VHL, neurofibromatosis type-1). OUTLINE: Patients receive lenvatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 or 6 months for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Mayo Clinic
Rochester, Minnesota, United States
Confirmed Tumor Response Rate
Will be defined as 100% times the number of eligible patients who has started lenvatinib and whose objective tumor status was a complete response or partial response on 2 consecutive evaluations at least 4 weeks apart (using Response Evaluation Criteria in Solid Tumors version 1.1 criteria) divided by the number of eligible patients who has started lenvatinib. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Monthly, up to 17 months.
Duration of Tumor Response
Will be estimated using the Kaplan-Meier method.
Time frame: Every month until off treatment, at off treatment, every 3 months until PD, at PD, every 6 months after PD up to 17 months
Patients Evaluable for Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 4.0
Adverse Events are fully reported in the adverse event section of the results. All adverse events will be graded. For each type of adverse event classified as either possibly, probably, or definitely related to study treatment, the proportion of patients experiencing a severe (grade 3 or higher) adverse event will be noted per cycle. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns.
Time frame: Monthly, up to 17 months.
Overall Survival Time
Will be estimated using the Kaplan-Meier method.
Time frame: Every month until off treatment, at off treatment, every 3 months until PD, at PD, every 6 months after PD up to 17 months
Progression-free Survival
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Will be estimated using the Kaplan-Meier method.
Time frame: Every month until off treatment, at off treatment, every 3 months until PD, at PD or up to 17 months
Quality of Life Assessed by EQ-5D and FACT-G
Descriptive statistics, and scatter plots will form the basis of presentation of these data both overall and by other outcomes (toxicity, response and survival measures). Correlations between the quality of life outcomes and other outcome measures will be carried out by standard parametric and nonparametric tests (e.g. Pearson's and Spearman's rho). Comparison between continuous variables will be made with Wilcoxon rank sum tests, Fisher's exact tests will be used to determine differences between categorical variables, and Log-rank test will be used to test differences between time-to-event ou
Time frame: 5 years