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

NCT03008369 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: MC1575NCI-2016-02032P30CA015083
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Malignant Adrenal Gland Pheochromocytoma; Malignant Paraganglioma; Metastatic Adrenal Gland Pheochromocytoma

Outcome Measures

Primary Outcomes (1)

• 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

  Monthly, up to 17 months.

Secondary Outcomes (5)

• Duration of Tumor Response

  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

  Monthly, up to 17 months.

• Overall Survival Time

  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

  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

  5 years

Other Outcomes (3)

• Changes in Urinary Catecholamine and Metanephrine Levels

  Up to 5 years

• Germline Mutational Status in Peripheral Blood Mononuclear Cells

  Up to 5 years

• Somatic Mutational Status in Peripheral Blood Mononuclear Cells

  Up to 5 years

Study Arms (1)

Treatment (lenvatinib)

EXPERIMENTAL

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; Drug: Lenvatinib; Other: Quality-of-Life Assessment

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (lenvatinib)

Lenvatinib DRUG

Given PO

Also known as: E7080, ER-203492-00, Multi-Kinase Inhibitor E7080

Treatment (lenvatinib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (lenvatinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed malignant secretory or non-secretory pheochromocytoma or paraganglioma that is unresectable and deemed inappropriate for alternative local regional therapeutic approaches
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Life expectancy \> 24 weeks
• Absolute neutrophil count (ANC) \>= 1500/mm\^3
• White blood cell (WBC) count \>= 3,000/mm\^3
• Platelet count \>= 100,000/mm\^3
• Hemoglobin \>= 9.0 g/dL (5.6 mmol/L); NOTE: transfusions are not allowed =\< 7 days prior to registration
• Total bilirubin =\< 1.5 X upper limit of normal (ULN) (or total bilirubin =\< 3.0 X ULN with direct bilirubin =\< 1.5 X ULN in patients with well-documented Gilbert's Syndrome)
• Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 2.5 X ULN
• Creatinine =\< 1.5 x ULN
• Urine protein/creatinine ratio =\< 1 OR 24-hour urine protein \< 1.5 gram
• Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
• Blood pressure (BP) \< 150 mmHg (systolic) and \< 90 mmHg (diastolic); initiation or adjustment of BP medication is permitted prior to registration provided that the average of three BP readings at a visit prior to registration is \< 150/90 mmHg; NOTE: all patients with secretory pheochromocytoma or paraganglioma are REQUIRED to: 1) be evaluated in consultation by a hypertension specialist with specific experience in the management of hypertension in the setting of catecholamine-secreting tumors (usually an endocrinologist, nephrologist, or a cardiologist), and in the setting of hormone-associated hypertension) receive alpha- and beta-adrenergic blockade for at least 7-14 days prior to initiation of lenvatinib; the hypertension specialist of record for each patient should be committed to closely following the patient during the clinical study with evaluation by said specialist required at cycle 1 and 2 and thereafter on an as needed basis
• Provide written informed consent

You may not qualify if:

• Any of the following:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Chemotherapy/systemic therapy, radiotherapy, immunotherapy or surgery =\< 21 days prior to registration or kinase inhibitor therapy =\< 14 days prior to registration or failure to recover from toxicities (to grade 1 or below) from treatment; NOTE: concurrent therapy with octreotide is allowed providing that tumor progression on this therapy has been demonstrated; concurrent therapy with bisphosphonates (e.g. zoledronic acid) or denosumab is also allowed; NOTE: an unlimited number of prior chemotherapeutic or biologic therapies for malignant pheochromocytoma or paraganglioma is permitted; this includes prior anti-angiogenesis therapies such as tyrosine kinase inhibitors
• Active or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving any other investigational agent
• Current use of warfarin for any reason; NOTE: if patient can be safely transitioned to another anticoagulant, they may be eligible provided other criteria are satisfied
• Any of the following:
• Correct QT (QTc) prolongation (defined as a QTc interval \>= 500 msecs)
• Left ventricular ejection fraction (LVEF) \< institutional lower limits of normal (LLN)
• Frequent ventricular ectopy
• Evidence of ongoing myocardial ischemia
• Receiving any medications or substances with risk of torsades de pointes; NOTE: medications or substances with known risk of torsades de pointes are prohibited; consult pharmacist for review if needed
• Known active and/or untreated brain metastases

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Paraganglioma, Extra-Adrenal; Pheochromocytoma

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Paraganglioma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Ashish Vitthalrao Chintakuntlawar, MBBS, Ph.D.
• Organization: Mayo Clinic

Chintakuntlawar.Ashish@mayo.edu

5072930504

Study Officials

• Ashish Chintakuntlawar

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2016
• First Posted: January 2, 2017
• Study Start: May 31, 2017
• Primary Completion: December 1, 2020
• Study Completion: September 28, 2022
• Last Updated: February 20, 2024
• Results First Posted: May 14, 2021

Record last verified: 2024-01

Locations

US (1)