Medullary thyroid cancer [MTC] or radioiodine (131*I) refractory/resistant differentiated thyroid cancer[DTC]: Determine the pharmacokinetic (PK) profile and the pharmacokinetic/pharmacodynamic (PK/PD) relationships of E7080. Note: *= to the power. MedDRA version: 9.1 Level: LLT Classification code 10065252 Term: Solid tumor
Conditions
Interventions
Product Name: HOPE
Product Code: E7080
Pharmaceutical Form: Film-coated tablet
Sponsors
Eisai Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the inclusion criteria to be eligible to participate in this study. 1. Patients must have histologically or cytologically confirmed diagnosis of one of the following: A. DTC, including any of the following subtypes: a. 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, Hürthle cell variant of papillary carcinoma, poorly differentiated) b. Follicular thyroid cancer (FTC) • Hürthle cell • Clear cell • Insular B. MTC 2. Measurable disease meeting the following criterion: a.At least 1 lesion (= 1.5 cm in longest diameter for non-lymph nodes and =2.0 cm in longest diameter for lymph nodes) which is serially and accurately measurable according to Modified RECIST using either CT/MRIRadiographically b.Lesions that have had EBRT must show evidence of progressive disease based on Modified RECIST to be deemed a target lesion 3. Patients must show evidence of disease progression by RECIST using site assessment of CT/MRI scans within 12 months (+1 month to allow for variances in patient scanning intervals) prior to study entry. 4. Patients with DTC must be 131*I refractory/resistant as defined by at least one of the following: a. One or more measurable lesions that have never demonstrated 131*I uptake on any radioiodine scan based on either collected scans or reports, b. One or more measurable lesions with disease progression by RECIST within 12 months (+1 month to allow for variances in patient scanning intervals) of 131I therapy despite 131*I uptake on radioiodine scan based on site assessment of CT/MRI scans. c. Cumulative activity of 131*I of >600 mCi or 22 gigabequerel (GBq), with the last dose administered at least 6 months prior to study entry. 5. Patients must have unresectable disease. Patients must not be amenable to surgery. 6. Patients with DTC must be receiving thyroxine suppression therapy and TSH should not be elevated (TSH > 5.50 mcu/mL). When tolerated by the patient, thyroxine dose should be changed to achieve TSH suppression (TSH < 0.50 mcu/mL) and this dose can be changed concurrently upon starting E7080. 7. Patients must not have had chemotherapy, major surgery, monoclonal antibody therapy or experimental therapy within the 30 days prior to the start of E7080 administration (6 weeks for nitrosoureas or mitomycin C). • Prior exposure to receptor tyrosine kinase inhibitors and antiangiogenic agents (including but not limited to AEE788, AG-013736, AMG706, AZD2171, bevacizumab, CP-547,632, dasatinib, enzataurin, imatinib mesylate, lenalidomide, pazopanib, sorafenib, sunitinib, thalidomide, vatalanib [PTK787/ZK 222584], VEGF Trap, and ZD6474) are allowed with at least 30 days between this therapy and the start of E7080 treatment. 8. All chemotherapy or radiation-related toxicities must have resolved to < Grade 2 severity, except alopecia and infertility. 9. Prior thyroidectomy is allowed. 10. Blood pressure should be wel
Exclusion criteria
Exclusion criteria: Patients with any one of the following are not eligible to participate in this study: 1. Anaplastic thyroid carcinoma, thyroid lymphoma, mesenchymal tumors of the thyroid, metastases to the thyroid. 2. Any of the following laboratory measurements: a. hemoglobin 1.5 times the upper limit of normal (ULN) and other liver function tests (AST, ALT and alkaline phosphatase) with values greater than three times ULN; (in the case of liver metastases > five times ULN). If alkaline phosphatase is greater than three times the ULN (in the absence of liver metastasis) or greater than five times the ULN (in the presence of liver metastasis), and the patient is known to have bone metastasis, the liver specific alkaline phosphatase must be separated from the total and the liver specific alkaline phosphatase alone should be used to assess liver function. d. renal function with serum creatinine > 1.5 ULN and/or creatinine clearance NYHA Class II, unstable angina or myocardial infarction within 6 months of study start, or serious cardiac arrhythmia). 4. Active hemoptysis (bright red blood of at least ½ teaspoon) in the 28 days prior to study entry. 5. Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, with a therapeutic international normalized ratio (INR). 6. Positive history of HIV, active hepatitis B or active hepatitis C or severe/uncontrolled intercurrent illness or infection. 7. Organ allografts requiring immunosuppressive treatment 8. Prior malignancy, other than non-melanoma skin cancer or cervical carcinoma in situ, unless the prior malignancy was diagnosed and definitively treated = 5 years previously with no subsequent evidence of recurrence 9. Brain or leptomeningeal (central nervous system [CNS]) metastases. Patients with stable or previously irradiated brain metastases are also excluded 10. Marked baseline prolongation of QT/QTc interval (QTc interval = 500 msec) using the Fridericia method (QTc = QT/RR0*.33) for QTc analysis 11. > 1+ proteinuria on urine dipstick testing or >30 mg/dL 12. History of gastrointestinal malabsorption or having undergone surgery requiring gastrointestinal anastomoses within 4 weeks of starting therapy or who have not recovered from major surgery within 4 weeks of starting therapy. 13. Women who are pregnant or breast-feeding; women of childbearing potential with a positive pregnancy test at screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception (including two forms of contraception, one of which must be a barrier method) in the opinion of the investigator. • Perimenopausal women must be amenorrheic for at least 12 months to be considered of non childbearing potential. • Fertile males with female partners who are not willing to use contraception or whose female partners are not using adequate cont
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Key outcomes measured • Overall tumor response rates of complete response (CR), and partial response (PR) based on modified RECIST assessed by IIR. ; Main Objective: In patients with medullary thyroid cancer [MTC] or radioiodine (131*I) refractory/resistant differentiated thyroid cancer[DTC]: • Determine the effect of E7080 on the objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) by independent imaging review (IIR). Note: * = to the power. ;Secondary Objective: Determine the effect of E7080 on duration of response by IIR, Measure effect on the disease control rate (DCR) and clinical benefit rate by IIR, Determine time to response by IIR, Evaluate effect on progression free survival by IIR and overall survival, Evaluate safety and tolerability, Determine PK profile and PK/PD relationship, Assess the influence of DNA sequence variants on metabolic enzymes and transporters possibly involved in variability of PK parameters, Determine biochemical response using tumor markers (thyroglobulin for DTC patients or calcitonine and CEA for MTC patients), Assess effect of somatic DNA sequence variants in BRAF, H-, Kand N-Ras and RET/PTC1, 2 and 3 and germline DNA sequence variants in RET and near FOXE1(rs965513) and NKX2-1 (rs944289) on patient response to study treatment, Investigate potential correlation of the following biomarkers with efficacy: Serum proteome expression, Serum biomarkers of apoptosis (CASP 3/7, Cytochrome C and M-30 neo-antigen) | — |
Countries
France, Italy, Poland, United Kingdom
Outcome results
None listed