Multicenter randomized open-label phase III trial of Adjuvant Chemotherapy vs. observation or mitotane after primary surgical resection of localized

INTERVENTION: Trade Name: CISPLATINO ACCORD HEALTHCARE ITALIA ‐ 1MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO IN VETRO DA 10 ML Product Name: CISPLATINO Product Code: [CISPLATINO] Pharmaceutical Form: Solution for infusion INN or Proposed INN: CISPLATINO Current Sponsor code: NA Other descriptive name: CISPLATINO Concentration unit: mg/m2 milligram(s)/square meter Concentration type: up to Concentration number: 80‐ Trade Name: ETOPOSIDE TEVA ‐ 1 FLACONE 10 ML 20MG/ML Product Name: etoposide Product Code: [etoposide] Pharmaceutical Form: Solution for injection INN or Proposed INN: ETOPOSIDE Current Sponsor code: etoposide Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 100‐ Trade Name: LYSODREN ‐ 500 MG‐COMPRESSE‐USO ORALE‐FLACONE(HDPE) 100 COMPRESSE Product Name: mitotano Product Code: [mitotano] Pharmaceutical Form: Tablet INN or Proposed INN: MITOTANO Current Sponsor code: mitotano Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1‐ CONDITION: localized Adrenocortical CarcInomA with high risk of recurrence ; MedDRA version: 20.0 Level: PT Classification code 10001388 Term: Adrenocortical carcinoma System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] SECONDARY OUTCOME: Secondary end point(s): serius event adverse Timepoint(s) of evaluation of this end point: every time in the study INCLUSION CRITERIA: Histologically confirmed diagnosis of ACC (Weiss score of = 3); all tumor specimens can be reviewed a posteriori by a reference pathologis ‐ High risk of relapse within 60 days of surgical resection of primary tumor with curative intent with either microscopically complete resection (R0, microscopically positive margins (R1), or undetermined margins (RX, based on surgical or pathological reports without unequivocal evidence of metastasis in the perioperative imaging). ‐ Ki67=10% (to be determined by an experienced pathologist in each participating center and preferably via quantitative imaging analysis). ‐ Have perioperative imaging (CT with contrast or MRI of the chest/abdomen/pelvis) demonstrating no unequivocal evidence of disease within 4 weeks before randomization. Patients with indeterminate non‐specific nodules (<1 cm for soft tissue lesions and <1.5 cm in the short dimension for lymph nodes) will be permitted to participate in this study.