Clinical Trial: Lenvatinib in Treating Patients With Metastatic or Advanced Pheochromocytoma or Paraganglioma That Cannot Be Removed by Surgery

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Phase II Trial of Lenvatinib in Metastatic or Advanced Pheochromocytoma and Paraganglioma

Brief Summary: 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.

Detailed Summary:

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
Sponsor: Mayo Clinic

Current Primary Outcome: Confirmed tumor response rate [ Time Frame: Up to 5 years ]

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. Ninety-five percent confidence intervals for the true response proportion will be calculated according to the approach of Duffy and Santner.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Duration of tumor response [ Time Frame: Up to 5 years ]
    Will be estimated using the Kaplan-Meier method.
  • Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ]
    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.
  • Overall survival time [ Time Frame: Time from registration to death due to any cause, assessed up to 5 years ]
    Will be estimated using the Kaplan-Meier method.
  • Progression-free survival [ Time Frame: Time from registration to documentation of disease progression, assessed up to 5 years ]
    Will be estimated using the Kaplan-Meier method.
  • Quality of life assessed by EQ-5D and FACT-G [ Time Frame: Up to 5 years ]
    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


Original Secondary Outcome: Same as current

Information By: Mayo Clinic

Dates:
Date Received: December 28, 2016
Date Started: April 2017
Date Completion: February 2020
Last Updated: March 6, 2017
Last Verified: January 2017