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

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ClinicalTrials.gov Identifier: NCT03506048
Recruitment Status : Recruiting
First Posted : April 23, 2018
Last Update Posted : January 23, 2019
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Taofeek K. Owonikoko, Emory University

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.

Condition or disease Intervention/treatment Phase
Differentiated Thyroid Gland Carcinoma Thyroid Gland Follicular Carcinoma Thyroid Gland Papillary Carcinoma Drug: Lenvatinib Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Lenvatinib in Combination With Radioactive Iodine Therapy in Patients With Progressive RAI-Sensitive Differentiated Thyroid Cancer
Actual Study Start Date : January 16, 2019
Estimated Primary Completion Date : January 31, 2021
Estimated Study Completion Date : January 31, 2021


Arm Intervention/treatment
Experimental: 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.
Drug: Lenvatinib
Given orally once daily continuously
Other Names:
  • E7080
  • ER-203492-00
  • Multi-Kinase Inhibitor E7080




Primary Outcome Measures :
  1. Time-to-progression [ Time Frame: Up to 2 years after study start ]
    The censored time-to-treatment failure will be estimated with standard Kaplan-Meier methodology. Both point and 90% confidence interval estimates of the median and other statistics (e.g., 3-month rate, 6-month rate, etc.) from the censored time-to-treatment failure distribution will be calculated.


Secondary Outcome Measures :
  1. Best objective response [ Time Frame: Up to 2 years after study start ]
    Patients will be assigned one of the following categories: complete response (CR), partial response (PR), stable disease (SD), progressive disease, non-evaluable, and disease control (CR + PR + SD). The same method of assessment and the same technique will be used to characterize each identified and reported lesion at baseline and during follow-up.

  2. Change in thyroglobulin levels [ Time Frame: Baseline up to 2 years ]
    Will assess dynamic changes in thryoglobulin levels. Levels at baseline will be a reference point.

  3. Change in thyroglobulin antibody levels [ Time Frame: Baseline up to 2 years ]
    Will assess dynamic changes in thryoglobulin antibody levels. Levels at baseline will be a reference point.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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): NCT03506048


Contacts
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Contact: Taofeek K. Owonikoko, MD, PhD 404-778-4995 towonik@emory.edu

Locations
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United States, Georgia
Emory University Hospital/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Shantina Walls    404-778-4995    shantina.n.walls@emory.edu   
Sponsors and Collaborators
Emory University
Eisai Inc.
Investigators
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Principal Investigator: Taofeek K. Owonikoko, MD, PhD Emory University

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Responsible Party: Taofeek K. Owonikoko, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT03506048     History of Changes
Other Study ID Numbers: IRB00101617
NCI-2018-00144 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Winship4271-18 ( Other Identifier: Emory University Hospital/Winship Cancer Institute )
First Posted: April 23, 2018    Key Record Dates
Last Update Posted: January 23, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Thyroid Neoplasms
Carcinoma, Papillary
Thyroid Cancer, Papillary
Adenocarcinoma, Follicular
Thyroid Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Neoplasms, Squamous Cell
Adenocarcinoma, Papillary
Adenocarcinoma
Iodine
Lenvatinib
Anti-Infective Agents, Local
Anti-Infective Agents
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action