Lenvatinib and Iodine Therapy in Treating Patients With Radioactive Iodine-Sensitive Differentiated Thyroid Cancer

NCT ID: NCT03506048

Last Updated: 2022-11-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-16
• Study Completion Date: 2021-06-24

Brief Summary

This phase II trial studies how well lenvatinib works when given together with standard of care iodine I-131 in treating patients with radioactive iodine-sensitive differentiated thyroid cancer. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of lenvatinib pretreatment along with radioactive iodine (RAI) in patients with previously treated RAI sensitive thyroid cancer.

SECONDARY OBJECTIVES:

I. To demonstrate the safety of the combination of lenvatinib and RAI in patients with Iodine sensitive differentiated thyroid carcinoma (DTC).

II. To assess dynamic changes in established serum based biomarkers of DTC (thyroglobulin [Tg] and Tg antibody).

III. To explore the utility of protein and genetic biomarkers to predict treatment efficacy.

OUTLINE:

Patients receive lenvatinib orally (PO) once daily (QD) for 8 weeks and up to 12 weeks in the absence of disease progression or unaccepted toxicity. Patients also receive iodine I-131 PO daily as standard of care.

After completion of study treatment, patients are followed up within 6 weeks, every 3 months for 1 year, and then periodically thereafter.

Conditions

Differentiated Thyroid Gland Carcinoma; Thyroid Gland Follicular Carcinoma; Thyroid Gland Papillary Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (lenvatinib)

Patients receive lenvatinib PO QD for 8 weeks and up to 12 weeks in the absence of disease progression or unaccepted toxicity. Patients also receive radioactive iodine (RAI) I-131 orally as standard of care.

Group Type: EXPERIMENTAL

Lenvatinib

Intervention Type: DRUG

Given orally once daily continuously

Interventions

Lenvatinib

Given orally once daily continuously

Intervention Type: DRUG

Other Intervention Names

E7080; ER-203492-00; Multi-Kinase Inhibitor E7080

Eligibility Criteria

Inclusion Criteria

• Prior treatment with therapeutic dose of radioactive iodine (> 50 mCi) with evidence of RAI uptake on delayed scan and with progression (biochemical or anatomic) within 12 months of RAI
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky ≥ 80%)
• Leukocytes ≥ 3,000/µL
• Absolute neutrophil count ≥ 1,500/µL
• Platelets ≥ 100,000/µL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional upper limit of normal
• Creatinine within normal institutional limits OR
• Creatinine clearance ≥ 60 mL/min/1.73 m² for patients with creatinine levels above institutional normal
• Confirmed diagnosis of differentiated thyroid cancer (follicular or papillary thyroid cancer and their variants)
• Ability and willingness to use appropriate contraception; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 2 weeks after completion of lenvatinib administration
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) by chest x-ray or as ≥ 10 mm (≥ 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients who have received RAI within 12 weeks of planned retreatment
• Prior receipt of cumulative RAI doses in excess of 1000 mCi
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1)
• Patients who are receiving any other investigational agents
• Patients with previously untreated and or symptomatic brain metastases are excluded from this clinical trial because of the risk of intracranial bleeding with angiogenic agents and tumoral swelling from RAI
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenvatinib
• 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
• Patients with uncontrolled hypertension (requirement for more than 2 blood pressure [BP] medications or grade 2 or higher BP elevation while on adequate doses of not more than 2 antihypertensive agents) are excluded from the study because one of the significant adverse events of lenvatinib is worsening hypertension
• Fridericia's corrected QT (QTcF) interval prolongation greater than 500 ms
• Recent arterial thromboembolic event within the previous 6 months
• Urine dipstick proteinuria ≥ 2+ or nephrotic range proteinuria on ≥ 2 gram in 24-hour urine
• History of gastrointestinal perforation, abscess or fistula
• History of and or medical condition (e.g. diverticular disease; aneurysm) that predisposes to risk of major hemorrhage
• Pregnant women are excluded from this study because lenvatinib is a tyrosine kinase inhibitor agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenvatinib, breastfeeding should be discontinued if the mother is treated with lenvatinib
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with lenvatinib

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Taofeek K. Owonikoko

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Taofeek K. Owonikoko, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2018-00144

Identifier Type: REGISTRY

Identifier Source: secondary_id

Winship4271-18

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00101617

Identifier Type: -

Identifier Source: org_study_id