Clinical Trials /

Lenvatinib in Locally Advanced Invasive Thyroid Cancer

NCT04321954

Description:

This research is being done to evaluate the safety and efficacy of neoadjuvant lenvatinib on surgical outcomes of patients with invasive extrathyroidal differentiated thyroid cancer (DTC). This research study involves a study drug called lenvatinib

Related Conditions:
  • Malignant Thyroid Gland Neoplasm
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Lenvatinib in Locally Advanced Invasive Thyroid Cancer
  • Official Title: A Phase 2 Study of Neoadjuvant Lenvatinib in Locally Advanced Invasive Thyroid Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19-524
  • NCT ID: NCT04321954

Conditions

  • Differentiated Thyroid Cancer
  • Advanced Cancer

Interventions

DrugSynonymsArms
LENVATINIBLenvimaLENVATINIB

Purpose

This research is being done to evaluate the safety and efficacy of neoadjuvant lenvatinib on surgical outcomes of patients with invasive extrathyroidal differentiated thyroid cancer (DTC). This research study involves a study drug called lenvatinib

Detailed Description

      This is a multicenter, phase II, open-label study examining the effect of neoadjuvant
      lenvatinib being given to patients with extrathyroidal differentiated thyroid cancer (DTC)
      prior to surgery to remove cancerous tumors (thyroidectomy).

      - The research study procedures include screening for eligibility and study treatment
      including evaluations and follow up visits.

        -  This research study involves a study drug called lenvatinib.

        -  It is anticipated that 30 people will participate in the study.

      The U.S. Food and Drug Administration (FDA) has not approved lenvatinib for the specific
      disease of extrathyroidal differentiated thyroid cancer (DTC) but it has been approved for
      other uses.

      Phase II clinical trials test the safety and effectiveness of an investigational drug to
      learn whether the drug works in treating a specific disease. "Investigational" means that the
      drug is being studied.
    

Trial Arms

NameTypeDescriptionInterventions
LENVATINIBExperimentalStudy procedures include screening for eligibility and study treatment, evaluations, and follow up visits Lenvatinib will be administered orally daily at a predetermined dose for 2 or 4 cycles, dependent on response. 1 cycle is 28 days. Surgery per standard of care will follow lenvatinib treatment.
  • LENVATINIB

Eligibility Criteria

        Inclusion Criteria:

          -  18 years of age at the time of informed consent and willing and able to provide
             written informed consent for the trial.

          -  Adult participants who are either initially diagnosed with locally advanced thyroid
             neoplasm or have experienced persistent or recurrent thyroid and/or cervical nodal
             recurrent DTC (participants with M1 disease are allowed, AJCC 8th edition stage
             I-IVb)), including:

               -  a. Papillary thyroid carcinoma (PTC) - classical and variants

                    -  Follicular variant

                    -  Variants including but not limited to tall cell, columnar cell,
                       cribriform-morular, solid, oxyphil, Warthin's-like, trabecular, tumor with
                       nodular fasciitis-like stroma, Hürthle cell variant of papillary carcinoma

               -  b. Follicular thyroid carcinoma (FTC)

               -  c. Hürthle cell carcinoma

               -  d. Poorly differentiated thyroid carcinoma

               -  e. Cytologically confirmed thyroid neoplasm, Bethesda 3, 4 and 5

          -  Evidence of extrathyroidal extension and/or locally invasive disease and deemed at
             risk for R2 resection by treating team on clinical and/or fiberoptic examination
             and/or radiographic evaluation in the primary or recurrent setting. Evidence of "at
             risk for R2 resection" includes:

               -  a. Vocal cord paralysis by fiberoptic examination

               -  b. Extrathyroid and/or extranodal extension on CT or MRI, including tracheal
                  and/or laryngeal cartilage invasion, esophageal involvement, and/or involvement
                  of perithyroid muscles (e.g. strap, sternocleidomastoid, inferior constrictor
                  muscles) or bone involvement

               -  c. Extension into the mediastinum with visceral and/or vascular involvement

               -  d. Involvement of the carotid artery or other major vessel by 180 degrees or more
                  (exclusive of complete encasement)

               -  e. Other factors that make the participant to be "at risk for R2 resection" may
                  be allowed, after discussion with the study's principal investigator.

          -  Measurable disease by RECIST v1.1.

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1 and no medical
             contraindication to surgery.

          -  Adequately controlled blood pressure.

               -  Blood pressure ≤150/90 with or without antihypertensive medications at screening

          -  Adequate end-organ function (including bone marrow, coagulation, renal, liver and
             cardiac) 28 days prior to the study registration as defined below:

               -  leukocytes ≥3,000/mcL

               -  absolute neutrophil count ≥1,500/mcL

               -  platelets ≥100,000/mcL

               -  total bilirubin ≤1.5 x institutional upper limit of normal, unless attributed to
                  Gilberts syndrome

               -  AST/ALT/Alk Phos ≤3 x institutional upper limit of normal

               -  INR ≤1.5 x institutional upper limit of normal

               -  creatinine within normal institutional limits OR

               -  creatinine clearance ≥30 mL/min per Cockcroft-Gault formulation

                    -  The cycle 1 day 1 labs need to re-meet eligibility criteria for treatment

          -  Ability to swallow pills.

          -  Females must not be lactating or pregnant at baseline (as documented by a negative
             betahuman chorionic gonadotropin [ß-hCG] test with a minimum sensitivity of 25 IU/L or
             equivalent units of ß-hCG. A separate baseline assessment is required if a negative
             screening pregnancy test was obtained more than 72 hours before the first dose of
             study drug.

          -  Note: All females will be considered to be of childbearing potential unless they are
             postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age
             group and without other known or suspected cause) or have been sterilized surgically
             (ie, bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with
             surgery at least 1 month before dosing).

          -  Females of childbearing potential must not have had unprotected sexual intercourse
             within 30 days before study entry and must agree to use a highly effective method of
             contraception (eg, total abstinence, an intrauterine device, a contraceptive implant,
             an oral contraceptive, or have a vasectomized partner with confirmed azoospermia)
             throughout the entire study period and for 30 days after study drug discontinuation.

        Females who are using hormonal contraceptives must have been on a stable dose of the same
        hormonal contraceptive product for at least 4 weeks before dosing and must continue to use
        the same contraceptive during the study and for 30 days after.

        Exclusion Criteria:

          -  Diagnosis of medullary thyroid carcinoma or anaplastic (undifferentiated) thyroid
             carcinoma.

          -  Radiographically identified following findings:

               -  intraluminal airway tumor

               -  complete carotid encasement/infiltration

          -  Active hemoptysis (bright red blood ≥ 1/2 teaspoon) or other uncontrolled bleeding
             within 21 days prior to the study registration.

          -  Arterial/venous thromboembolic events in the last 12 months Treatment within 30 days
             prior to study registration with anticoagulant or antiplatelet therapy, apart from
             aspirin 81 mg daily.

          -  Prior radiotherapy to the neck.

          -  Prior treatment with lenvatinib or other VEGFR-directed therapy, including sorafenib.

          -  Known metastasis to central nervous system.

          -  Females who are pregnant or breastfeeding.

          -  If > 1 + proteinuria on urine dipstick testing will undergo 24-hour urine collection
             for quantitative assessment of proteinuria. Participants with urine protein ≥1g/24 h
             will be ineligible.

          -  Gastrointestinal malabsorption or any other condition that in the opinion of the
             investigator might affect the absorption of study drug.

          -  Active infection requiring treatment.

          -  Significant cardiovascular impairment: history of congestive heart failure greater
             than New York Heart Association (NYHA) Class II, unstable angina, myocardial
             infarction, or stroke within 6 months of the first dose of study drug, or cardiac
             arrhythmia requiring medical treatment.

          -  Prolongation of corrected QT interval (QTc) to > 480 ms as demonstrated by a repeated
             ECG or any clinically significant ECG abnormality

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to lenvatinib.

          -  Any medical or other condition that in the opinion of the investigators would preclude
             participant's participation in a clinical study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall R0/R1 resection rate
Time Frame:112 Days
Safety Issue:
Description:Evaluate the overall R0/R1 resection rate, as defined by proportion of patients who undergo successful thyroidectomy with clear (R0) or microscopically positive surgical margins (R1).

Secondary Outcome Measures

Measure:Resection rate of R0
Time Frame:112 Days
Safety Issue:
Description:Evaluate R0 resection rates in each of 4 pre-specified extrathyroidal anatomic target interfaces: R0=no cancer cells seen microscopically at the resection margin
Measure:Resection rate of R1
Time Frame:112 Days
Safety Issue:
Description:Evaluate R1 resection rates in each of 4 pre-specified extrathyroidal anatomic target interfaces: R1 cancer cells present microscopically at the resection margin (microscopic positive margin)
Measure:Change in Surgical complexity and morbidity score (SCMS)
Time Frame:112 Days
Safety Issue:
Description:The change in SCMS will be reported as the median SCMS value -Determined by structures requiring resection, the RGS takes into account preoperatively radiographically defined structures judged to be requiring resection with surgical complexity of the given resection/potential for complications, and expected patient morbidity/change of function from the resection.
Measure:Primary surgery response rate
Time Frame:112 Days
Safety Issue:
Description:Evaluate the response rate (RR) prior to primary surgery based on Response Evaluation Criteria in Solid Tumors version 1.1
Measure:Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v 5.0
Time Frame:Up to 18 months
Safety Issue:
Description:CTCAE version 5
Measure:Unresectable to resectable conversion rate
Time Frame:112 Days
Safety Issue:
Description:The conversion rate will be summarized as frequency (%) -- Determined by structures requiring resection, the RGS takes into account preoperatively radiographically defined structures judged to be requiring resection with surgical complexity of the given resection/potential for complications, and expected patient morbidity/change of function from the resection.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Massachusetts Eye and Ear Infirmary

Trial Keywords

  • Differentiated Thyroid Cancer
  • Advanced Cancer

Last Updated

March 24, 2020