I. To compare the effect of adjuvant mitotane treatment alone (arm A) with that of adjuvant mitotane combined with four 21-day cycles of etoposide/cisplatin (arm B) on recurrence-free survival (RFS) in patients with high-risk adrenocortical carcinoma (ACC) after initial surgical resection.
I. Assess overall survival (OS), defined as the time interval between the date of randomization and the date of death from any cause.
II. Assess the effect of serum mitotane levels, disease stage, and surgical resection margins on clinical outcomes.
III. Assess the effect of early start (1-6 weeks from surgery) versus (vs.) late start (> 6 weeks from surgery) of adjuvant therapy on clinical outcomes.
IV. Assess serious adverse events. V. Measure quality of life at baseline, 6 weeks, 6 months after the initiation of adjuvant therapy, and at the end of study participation (recurrence or completing study treatments) using a validated quality of life questionnaire (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30).
I. Perform molecular profiling on available tissue specimens obtained at the time of initial surgical resection (formalin-fixed paraffin-embedded or frozen tissues) to identify genomic alterations in primary tumors that are associated with the clinical end points.
II. Evaluate markers to detect ACC recurrence or predict response to therapy (including steroid hormones and precursors, circulating tumor cells, and micro ribonucleic acid [microRNA]).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive mitotane orally (PO) daily on days 1-21. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive mitotane as in Arm A. Patients also receive cisplatin intravenously (IV) over 2 hours on day 1 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. By listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.