Brief Title
Efficacy of Adjuvant Mitotane Treatment (ADIUVO)
Official Title
Efficacy of Adjuvant Mitotane Treatment in Prolonging Recurrence-free Survival in Patients With Adrenocortical Carcinoma at Low-intermediate Risk of Recurrence
Brief 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
Detailed Description
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.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Disease Free survival
Condition
Adrenocortical Carcinoma
Intervention
MITOTANE
Study Arms / Comparison Groups
Follow-up
Description: Arm B
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
200
Start Date
April 2008
Completion Date
December 2020
Primary Completion Date
December 2018
Eligibility 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Massimo Terzolo, MD, +390119026, [email protected]
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT00777244
Organization ID
EudraCT 2007-007262-38
Responsible Party
Principal Investigator
Study Sponsor
University of Turin, Italy
Study Sponsor
Massimo Terzolo, MD, Study Chair, Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Italy
Verification Date
May 2017