E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10001388 |
E.1.2 | Term | Adrenocortical carcinoma |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001388 |
E.1.2 | Term | Adrenocortical carcinoma |
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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 compare the efficacy of adjuvant mitotane treatment vs observation only in prolonging recurrence free survival in patients with ACC at low-intermediate risk of recurrence after complete resection. |
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E.2.2 | Secondary objectives of the trial |
- Comparison of Overall Survival (OS) - Comparison of time to recurrence (TTR) - Comparison of disease free survival (DFS) - Comparison of quality of life - Assessment of toxicity - Assessment of the impact of mitotane plasma levels and time needed to reach the therapeutic interval on the efficacy of treatment - Assessment of the efficacy of the mitotane administration on subgroups of patients stratified according to: type of hormone secretion, stage of disease, histopathologic characteristics. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed diagnosis of ACC • Low-intermediate risk of relapse defined as: • Stage I-III ACC (according to the ENS@T classification 2008) • Microscopically complete resection, defined as no evidence of microscopic residual disease based on surgical reports, histopathology and post-operative imaging • Ki 67 ≤ 10% • Post-operative imaging (thoracic and whole abdominal CT with contrast medium or MRI) demonstrating no evidence of disease within 4 weeks before randomization • Age ≥ 18 years • ECOG performance status 0-2 • Adequate bone marrow reserve (neutrophils ≥ 1000/mm3 and/or platelets≥ 80000/ mm3) • Ability to comply with the protocol procedures • Written informed consent
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E.4 | Principal exclusion criteria |
• Time between primary surgery and randomization >3 months. • Repeated surgery for recurrence of disease • Persistence of autonomous adrenocortical hormone secretion following surgery • History of recent or active prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies where there has been no evidence of disease for at least three years • Renal insufficiency (creatinine clearance < 40 ml/min) or liver insufficiency (serum bilirubin > 2 times the upper normal range and/or serum transaminases (AST, ALT) >3 times the upper normal range). Creatinine clearence may be calculated according to validated formulae (Crockoft’s or MDRD) • Pregnancy or breast feeding • Previous or current treatment with mitotane or other antineoplastic drugs for ACC • Previous radiotherapy for ACC
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E.5 End points |
E.5.1 | Primary end point(s) |
RFS, defined as the time between the date of randomization until documentation of any of the following failures (whichever occurs first): local or distant recurrence of ACC or death from any cause
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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 | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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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2 years after recruiting the 200. patient |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |