Clinical Trials /

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

NCT03506048

Description:

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.

Related Conditions:
  • Thyroid Gland Follicular Carcinoma
  • Thyroid Gland Papillary Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Lenvatinib and Iodine Therapy in Treating Patients With Radioactive Iodine-Sensitive Differentiated Thyroid Cancer
  • Official Title: A Phase 2 Study of Lenvatinib in Combination With Radioactive Iodine Therapy in Patients With Progressive RAI-Sensitive Differentiated Thyroid Cancer

Clinical Trial IDs

  • ORG STUDY ID: IRB00101617
  • SECONDARY ID: NCI-2018-00144
  • SECONDARY ID: Winship4271-18
  • NCT ID: NCT03506048

Conditions

  • Differentiated Thyroid Gland Carcinoma
  • Thyroid Gland Follicular Carcinoma
  • Thyroid Gland Papillary Carcinoma

Interventions

DrugSynonymsArms
LenvatinibE7080, ER-203492-00, Multi-Kinase Inhibitor E7080Treatment (lenvatinib)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (lenvatinib)ExperimentalPatients 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.
  • Lenvatinib

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time-to-progression
Time Frame:Up to 2 years after study start
Safety Issue:
Description: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

Measure:Best objective response
Time Frame:Up to 2 years after study start
Safety Issue:
Description: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.
Measure:Change in thyroglobulin levels
Time Frame:Baseline up to 2 years
Safety Issue:
Description:Will assess dynamic changes in thryoglobulin levels. Levels at baseline will be a reference point.
Measure:Change in thyroglobulin antibody levels
Time Frame:Baseline up to 2 years
Safety Issue:
Description:Will assess dynamic changes in thryoglobulin antibody levels. Levels at baseline will be a reference point.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Emory University

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