Details

Details

Title An Open-Label, Randomized, Multicenter, Expanded Access Program With Lenvatinib for the Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer

IRB ESAI1314

CC 14-1297

Hospital Main Campus

Disease Thyroid

Drug Lenvatinib

Description

Description

Primary Objectives
  1. Provide lenvatinib with a starting dose of either 24-mg, 20-mg, or 14-mg/day to subjects with RR-DTC who have failed the available standard of care treatment, have no other treatment options, and therapy is requested by their physician and,
  2. Provide pilot information on activity and safety of these doses that may be used in the design of future studies.
Inclusion Criteria

Inclusion Criteria

  1. Subjects must have histologically or cytologically confirmed diagnosis of one of the following DTC subtypes:
    1. Papillary thyroid cancer (PTC)
      • 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, Hurthle cell variant of papillary carcinoma, poorly differentiated).
    2. Follicular thyroid cancer (FTC)
      • Hurthle cell
      • Clear cell
      • Insular
  2. Subjects must be radioiodine-refractory or resistant within 12 months of radioiodine therapy and have one of the following:
    1. One or more lesions that do not demonstrate iodine uptake on any radioiodine scan
    2. One or more lesions that have substantially increased in size within 12 months of radioiodine therapy, despite demonstration of radioiodine activity at the time of that treatment by pre- or posttreatment scanning
    3. Cumulative activity of radioiodine of > 600 mCi or 22 gigabecquerels (GBq), with the last dose administered at least 6 months prior to study entry
  3. Subjects must have received and failed treatment with sorafenib for RR-DTC. This criterion will not apply outside the United States if sorafenib is not commercially available in the country where the subject resides.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  5. Blood pressure (BP) ≤150/90 mmHg at screening with or without antihypertensive medications and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1
  6. Creatinine clearance ≥30 mL/min according to the Cockcroft and Gault formula
  7. Adequate bone marrow function:
    1. Absolute neutrophil count (ANC) ≥1.5 x 109/L
    2. Hemoglobin ≥9.0 g/dL (can be corrected by growth factor or transfusion)
    3. Platelet count ≥100 x 109/L
  8. Adequate liver function:
    1. Bilirubin ≤1.5 x upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome
    2. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 x ULN (≤5 x ULN if subject has liver metastases). If ALP is >3 x ULN (in the absence of liver metastases) or >5 x ULN (in the presence of liver metastases) AND subjects are also known to have bone metastases, the liver-specific ALP must be separated from the total and used to assess the liver function instead of the total ALP
  9. Provide written informed consent
  10. Males and females, age ≥18 years at the time of informed consent
  11. 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 double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire program. If currently abstinent, subjects must agree to use a double-barrier method as described above if they become sexually active during the study period or 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 study drug discontinuation.
Exclusion Criteria

Exclusion Criteria

  1. Subjects having >1+ proteinuria on urine dipstick at screening testing will undergo 24 h urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥1 g/24 h will be ineligible.
  2. History of congestive heart failure with New York Heart Association (NYHA) Classification >II, unstable angina, myocardial infarction, serious cardiac arrhythmia, or stroke within the past 6 months
  3. Electrocardiogram (ECG) with QT interval (QTc) interval ≥480 msec
  4. Existing anti-cancer therapy-related toxicities of grade ≥2, except alopecia and infertility
  5. History of intolerance to or progression on prior treatment with lenvatinib that led to the discontinuation of lenvatinib
  6. Any history of or concomitant medical condition that, in the opinion of the investigator, would compromise subject's ability to safely complete the protocol
  7. Females who are pregnant (positive β-hCG test) or breastfeeding
  8. Eligible for any other lenvatinib study that is open for recruitment.