E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Differentiated Thyroid Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027485 |
E.1.2 | Term | Metastatic thyroid cancer scintigraphy |
E.1.2 | System Organ Class | 100000004848 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of selumetinib with radioactive iodine therapy (RAI), versus placebo with RAI, by assessment of complete remission rate at 18 months post RAI treatment in the intention to treat (ITT) study population. |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of selumetinib with RAI, versus placebo with RAI, by assessment of complete remission rate at 18 months post RAI treatment in a sub-group of patients with tumours known to be mutation positive for BRAF or NRAS.
To compare the efficacy of selumetinib with RAI, versus placebo with RAI by
assessment of clinical remission rate at 18 months post RAI treatment in the ITT study population.
To compare the efficacy of selumetinib with RAI, versus placebo with RAI by assessment of clinical remission rate at 18 months post RAI treatment in a sub-group of patients with tumours known to be mutation positive for BRAF or NRAS
To assess the safety and tolerability of selumetinib with RAI compared to placebo with RAI.
To investigate the pharmacokinetics (PK) of selumetinib and N-desmethyl selumetinib when administered to patients with differentiated thyroid cancer. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Confirmed follicular cell derived differentiated thyroid cancer
Post-surgery staging categories: primary tumor greater than 4 cm or gross extrathyroidal extension (T4 disease) or at least 1 lymph node that is 1 cm or larger or 5 or more involved lymph nodes (of any size)
Previous one or two stage total thyroidectomy with therapeutic neck dissection of metastatic lymph nodes
Patient must be suitable for radioactive iodine therapy
Patient must be suitable for TSH suppression
Patients must have all of the post-operative assessments (including neck US exam,
neck MRI with contrast, and chest CT without contrast) performed no
sooner than 4 weeks post-surgery and the results from each must verify the absence of macroscopic disease. |
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E.4 | Principal exclusion criteria |
Known distant metastatic disease at study entry
Diagnosis of anaplastic thyroid cancer, medullary thyroid cancer or Hurthle cell carcinoma
Presence of anti-Tg antibodies at screening
Previous treatment with 131 I (RAI) or external beam radiation therapy (EBRT)
Unresolved toxicity ≥ CTCAE Grade 2 from any previous therapy
Hypersensitivity to rhTSH and unwillingness to use rhTSH prior to RAT treatment
Previous treatment with any MEK or BRAF inhibitor |
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E.5 End points |
E.5.1 | Primary end point(s) |
Complete remission rate in the ITT study population |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Measured at 18 months post RAI treatment. |
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E.5.2 | Secondary end point(s) |
Clinical remission rate in the ITT study population.
Complete remission rate in sub-group of patients with tumours known to be mutation positive for BRAF or NRAS
Clinical remission rate in sub-group of patients with tumours known to be mutation positive for BRAF or NRAS
Frequency and severity of adverse events
Assess the pharmacokinetics of selumetinib and/or N-desmethyl selumetinib by assessment of parameters including area under the curve over time (AUC) and maximum concentration |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Measured at 18 months post RAI treatment
AE's Measured throughout the study until final study follow up.
PK - In total 8 blood samples will be collected: 4 samples on pre defined time windows on Day1, and 4 samples on Day 29 or Day 30 |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 | No |
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 |
Brazil |
Denmark |
France |
Germany |
Italy |
Poland |
Sweden |
United States |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |