Lenvatinib in Treating Patients With Metastatic or Advanced Pheochromocytoma or Paraganglioma That Cannot Be Removed by Surgery
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|ClinicalTrials.gov Identifier: NCT03008369|
Recruitment Status : Recruiting
First Posted : January 2, 2017
Last Update Posted : March 14, 2018
|Condition or disease||Intervention/treatment||Phase|
|Malignant Adrenal Gland Pheochromocytoma Malignant Paraganglioma Metastatic Adrenal Gland Pheochromocytoma||Other: Laboratory Biomarker Analysis Drug: Lenvatinib Other: Quality-of-Life Assessment||Phase 2|
I. To determine the anti-tumor activity of lenvatinib (overall response rate; [ORR]) in patients with metastatic or advanced unresectable pheochromocytomas and paragangliomas.
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).
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).
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 (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Lenvatinib in Metastatic or Advanced Pheochromocytoma and Paraganglioma|
|Actual Study Start Date :||May 31, 2017|
|Estimated Primary Completion Date :||February 2020|
|Estimated Study Completion Date :||February 2020|
Experimental: Treatment (lenvatinib)
Patients receive lenvatinib PO once daily on days 1-28. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
- 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.
- 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
- Changes in urinary catecholamine and metanephrine levels [ Time Frame: Up to 5 years ]Wilcoxon rank sum tests will be used to examine whether fold changes in a given biomarker during the first cycle of treatment differs between whose tumor responded to treatment and those whose tumor did not. Time series plots will be constructed.
- Germline mutational status in peripheral blood mononuclear cells [ Time Frame: Up to 5 years ]Will 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).
- Somatic mutational status in peripheral blood mononuclear cells [ Time Frame: Up to 5 years ]Will 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03008369
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Clinical Trials Referral Office 855-776-0015|
|Principal Investigator: Ashish V. Chintakuntlawar|
|Principal Investigator:||Ashish Chintakuntlawar||Mayo Clinic|