Efficacy of Adjuvant Mitotane Treatment (ADIUVO)

• Disease Free survival [ Time Frame: six years ] [ Designated as safety issue: Yes ]
  

Endpoints Primary : To compare DFS (Disease Free Survival), 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 disease;-death from any cause or completion of follow-up.

Secondary:

To compare OS (Overall Survival), defined as the time interval between the date of randomization and the date of death from any cause or the last known alive date;· To compare quality of life measured by EORTC-QLQ-C30· To compare toxicity, graded according to the NCI-CTG criteria;· To compare DFS and OS in patients who achieve or not serum mitotane concentrations > 14 mg/L;· To compare DFS and OS between the 2 arms in patients subgroups stratified according to: type of hormone secretion, stage of disease, histopathologic characteristics.

Inclusion Criteria · Histologically confirmed diagnosis of ACC· Low-intermediate risk of relapse defined as: · Stage I-III ACC· Microscopically complete resection, defined as no evidence of microscopic residual disease based on surgical reports, histopathology and post-operative imaging· Ki 67 < 10%· Age > 18 years· ECOG performance status 0-2· Adequate bone marrow reserve (neutrophils > 1000/mm3 and platelets > 80000/ mm3) Ability to comply with the protocol procedures (including geographic accessibility).· Written informed consent Exclusion Criteria · Time between primary surgery and randomization >3 months. · Repeated surgery for recurrence of disease· Presence of autonomous adrenocortical hormone secretion despite the absence of disease detectable with imaging techniques· History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with 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 clearance may be calculated according to validated formulas (Cockcroft's or MDRD)· Pregnancy or breast feeding· Previous or current treatment with mitotane or other antineoplastic drugs for ACC· Previous radiotherapy of the tumor bed· Any other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.