E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable locally advanced or metastatic medullary thyroid cancer |
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E.1.1.1 | Medical condition in easily understood language |
Advanced medullary thyroid cancer |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027105 |
E.1.2 | Term | Medullary thyroid cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
To assess the objective response rates (ORR) for 150 mg and 300 mg/day of vandetanib in patients with advanced & progressive MTC. ORR = % of patients with a best response of complete or partial response (CR/PR) as per RECIST Version1.1 |
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E.2.2 | Secondary objectives of the trial |
Safety, tolerability and pharmacokinetics of vandetanib 150 mg and 300 mg.
Time to and duration of objective response, and best percentage change in target lesion size in Part A.
Examine the relationship between PK and QTc
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Written consent from Female or male patients aged 18 years and over.
Previously confirmed histological diagnosis of unresectable, locally advanced or metastatic, hereditary or sporadic MTC
Objective disease progression within the previous 14 months prior to enrolment, and/or have one or more symptoms that the Investigator believes to be related to the patient’s MTC.
World Health Organisation (WHO) or Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
Has measurable disease (at least one lesion, not irradiated within12 weeks of study randomisation, with longest diameter ≥10mm (lymph nodes minimum ≥15 mm) with CT or MRI). Lesions must be amenable to accurate and repeat measurement. |
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E.4 | Principal exclusion criteria |
Prior treatment (major surgery, radiation therapy, chemotherapy, or other investigational drugs) received within 28 days before randomization.
Abnormal liver function tests (bilirubin>1.5xULRR, and ALT, AST, or ALP>2.5xULRR or 5.0xULRR if related to liver metastases).
Significant cardiac conditions or events such as reduced cardiac functions, symptomatic cardiac arrhythmia requiring treatment, congenital long QT syndrome, history of drug-induced QT prolongation, or QTcF correction unmeasurable or >450 ms
Abnormal electrolytes such as potassium, magnesium and calcium, or abnormal organ functions such as decreased creatinine clearance.
For women only - currently pregnant or breast feeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the objective response rates (ORR) for 150 mg and 300 mg/day of vandetanib in patients with advanced & progressive MTC. ORR = % of patients with a best response of complete or partial response (CR/PR) as per RECIST Version1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patient's disease status is measured every 12 weeks for up to14months after start of treatment or objective disease progression if earlier. |
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E.5.2 | Secondary end point(s) |
To evaluate the safety and tolerability of vandetanib 150 mg and 300 mg
To evaluate the time to objective response, duration of objective response, and the best percentage change in target lesion (TL) size while in Part A of the study
To evaluate the pharmacokinetics (PK) of vandetanib at 150 mg and 300 mg in this patient population
To examine the relationship between PK and QTcF (QT interval corrected for heart rate according to Fridericia)is applicable |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety monitored continuously and evaluated after 14 and 24 months. NB treatment is unblinded after 14 months or objective progression
Disease levels evaluated for 14months after start of treatment or objective disease progression if earlier.NB treatment is unblinded after 14 months or objective progression
At 3, 8, 12, 24 and 60 weeks after starting treatment and when objective disease progession is evident (if <60 weeks)
Safety monitored continuously and evaluated overall after 14 and 24 months. NB treatment is unblinded after 14 months or objective progression |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Czech Republic |
India |
Israel |
Italy |
Netherlands |
Poland |
Russian Federation |
United Kingdom |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |