Mitotane With or Without Cisplatin and Etoposide After Surgery in Treating Patients With Stage I-III Adrenocortical Cancer With High Risk of Recurrence
Start Date
8/20/2018
Completion Date
1/1/2029
Summary
This phase III trial studies how well mitotane alone works compared to mitotane with cisplatin and etoposide when given after surgery in treating patients with adrenocortical cancer that has a high risk of coming back (recurrence). Cortisol can cause the growth of adrenocortical tumor cells. Antihormone therapy, such as mitotane, may lessen the amount of cortisol made by the body. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether mitotane alone or mitotane with cisplatin and etoposide after surgery works better in treating patients with adrenocortical carcinoma.
Detailed Description
PRIMARY OBJECTIVE: 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. SECONDARY OBJECTIVES: 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). EXPLORATORY OBJECTIVES: 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.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Cisplatin
Etoposide
Mitotane
Quality-of-Life Assessment
Conditions
Locations
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan 48109
United States
Siteman Cancer Center at Washington University
St Louis, Missouri 63110
United States
M D Anderson Cancer Center
Houston, Texas 77030
United States
Institut de Cancérologie de l'Ouest (ICO)
Angers, 49055
France
CHU Angers, Hôpital Larrey
Angers, 49933
France
CHU Besançon, Hôpital Jean Minjoz
Besançon, 25000
France
CHU Brest, Hôpital La Cavale Blanche
Brest, 29200
France
Centre Georges François Leclerc
Dijon, 25000
France
Lyon HCL
Lyon, 69002
France
HCL Hôpital Louis Pradel
Lyon, 69877
France
Marseille Hôpital Nord
Marseille, 13015
France
Marseille Hôpital de la Conception
Marseille,
France
CHU Nantes, Hôpital René et Guillaume Laënnec
Nantes, 44093
France
CHU Nantes, Hôpital René et Guillaume Laënnec
Nantes, 44093
France
Hôpital Cochin, AP-HP
Paris, 75014
France
Hôpital Cochin, AP-HP
Paris, 75014
France
Hôpital Cochin
Paris, 75014
France
Hôpital COCHIN
Paris, 75014
France
CHU Bordeaux - Hôpital Haut Lévèque
Pessac, 33600
France
CHU Poitiers
Poitiers, 86000
France
CHU Reims
Reims, 51092
France
HUS, Hôpital Hautepierre
Strasbourg, 67000
France
Strasbourg HUS Hautepierre
Strasbourg, 67000
France
CHU Toulouse, Hôpital Larrey
Toulouse, 31059
France
CHU Toulouse, Hôpital Rangueil
Toulouse, 31400
France
Gustave Roussy
Villejuif, 94805
France
LMU Klinikum München
Munich, 80336
Germany
Universitätsklinikum Würzburg
Würzburg, 97080
Germany
Maria Sklodowska-Curie National Research Institute of Oncology
Gliwice, 44-102
Poland
Sahlgrenska University Hospital
Gothenburg,
Sweden
Skånes Universitetssjukhus
Lund,
Sweden
Karolinska University Hospital
Stockholm,
Sweden
Akademiska Sjukhuset
Uppsala,
Sweden