Trial Information

Efficacy of Adjuvant Mitotane Treatment in Prolonging Recurrence-free Survival in Patients With Adrenocortical Carcinoma at Low-intermediate Risk of Recurrence

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.