Efficacy of Adjuvant Mitotane Treatment (ADIUVO)

• Status: Unknown status
• Trial end date: 2020-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Study Rationale Adrenocortical carcinoma (ACC) is a very rare disease with a high risk of relapse after radical surgery. The efficacy of adjuvant mitotane treatment is suggested by a retrospective multicenter international study showing that postoperative mitotane treatment was associated with a significant reduction of the risk of relapse and death. However, these promising results need confirmation in a randomized prospective study. Caution should be adopted particularly in patients with low risk of disease relapse, in whom the benefit of therapy should be weighted against the side effects. Even if an adjuvant treatment seems justified in patients at high risk of relapse, a randomised prospective study is needed to assess whether such a treatment is efficacious in patients at low-intermediate risk.

The purpose of the present study is to determine whether adjuvant mitotane treatment is effective in prolonging the disease free survival in patients with adrenocortical carcinoma at low-intermediate risk of progression who underwent radical resection

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Turin, Italy
• Treatments: Mitotane

Criteria

Inclusion Criteria:

• Histologically confirmed diagnosis of ACC according to Weiss system by a national reference pathologist who has to be nominated before study initiation.

• Low-intermediate risk of relapse defined as:

• Stage I-III (according to ENSAT classification 2008; see Appendix 2)

• Microscopically complete resection, defined as no evidence of microscopic residual disease based on surgical reports, histopathology and post-operative imaging. Detailed pathological and surgical reports prepared according to guidelines detailed in appendix x and y should be available for assessment.

• Ki 67 < 10%

• Post-operative imaging (thoracic and whole abdominal CT with contrast medium or MRI) demonstrating no evidence of disease within 4 weeks from randomization

• Age > 18 years

• ECOG performance status 0-2 (Appendix 3)

• 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.

• Repeat 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/SGOT, ALT/SGPT, but not gamma Glutamyl Transpeptidase) >3 times the upper normal range). Creatinine clearance may be calculated according to validated formulas (Crockoft'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 (for ACC).

• 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.