E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Medullary thyroid cancer [MTC] or radioiodine(131I) refractory/resistant differentiated thyroid cancer[DTC]. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
In patients with medullary thyroid cancer [MTC] or radioiodine (131I) 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) Determine the pharmacokinetic (PK) profile and the pharmacokinetic/pharmacodynamic (PK/PD) relationships of E7080 |
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E.2.2 | Secondary objectives of the trial |
Determine the effect of E7080 on duration of response by IIR Measure the effect of E7080 on the disease control rate (DCR) and clinical benefit rate (CBR) by IIR Determine the time to response by IIR Evaluate the effect of E7080 on progression free survival (PFS) by IIR and overall survival (OS) Evaluate the safety and tolerability of E7080 Assess the influence of DNA sequence variants on metabolic enzymes and transporters possibly involved in variability of E7080 PK parameters by genotyping patients genomic DNA using the Affymetrix DMET array. (Added per Amendment 01) Determine the biochemical response using tumor markers (either thyroglobulin for patients with DTC or calcitonin and carcinoembryonic antigen [CEA] for patients with MTC) Assess the effect of somatic DNA sequence variants in BRAF, H-, K- and 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 tre |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must have histologically or cytologically confirmed diagnosis of MTC or DTC. Measurable disease meeting the following criteria (revised per Amendment 01): o at least one 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/MRI o Lesions that have had external beam radiotherapy (EBRT) must show evidence of progressive disease based on Modified RECIST to be deemed a target lesion 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 patients scanning intervals) prior to study entry (revised per Amendment 01). Patients with DTC must be 131I refractory/resistant defined by at least one of the following: a. One or more measurable lesions that have never demonstrated 131I 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 131I uptake on radioiodine scan based on site assessment of CT/MRI scans (revised per Amendment 01). c. Cumulative activity of 131I of >600 mCi or 22 gigabequerel (GBq), with the last dose administered at least 6 months prior to study entry. |
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E.4 | Principal exclusion criteria |
Anaplastic thyroid carcinoma, thyroid lymphoma, mesenchymal tumors of the thyroid, metastases to the thyroid Significant cardiovascular impairment (history of congestive heart failure > NYHA Class II, unstable angina or myocardial infarction within 6 months of study start, or serious cardiac arrhythmia) Active hemoptysis (bright red blood of at least � teaspoon) in the 28 days prior to study entry |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |