Primary objectiveTo compare the efficacy of adjuvant mitotane treatment vs observational follow-up only in prolonging recurrence free survival (RFS) in patients with ACC after complete resection and low-intermediate risk for disease recurrence.…
ID
Source
Brief title
Condition
- Adrenal gland disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Recurence 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 ACC
- death from any cause or completion of follow-up
Secondary outcome
- Overall survival, defined as the time between the date of randomization and
the date of of death from any cause
- Time to recurrence, defined as the time between the date of randomization
until documentation of local or distant recurrence of ACC, or death from ACC
- disease free survival, defined as the time between the date of randomization
until documentation of any relevant cancer disease, or death of any cause
(whichever occurs first)
- Quality of life measured by EORTC-QLQ-C30
Background summary
Adrenocortical carcinoma 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 agaisnt the side effects. Even if an adjuvant treatment
seems justified in patients at high risk of relapse, a randomized prospective
study is needed to assess whether such a treatment is efficacious in patients
at low-intermediate risk.
Study objective
Primary objective
To compare the efficacy of adjuvant mitotane treatment vs observational
follow-up only in prolonging recurrence free survival (RFS) in patients with
ACC after complete resection and low-intermediate risk for disease recurrence.
Secondary objectives
* Comparison of Overall Survival (OS)
* Comparison of time to recurrence (TTR)
* Comparison of disease free survival (DFS)
* Quality of life assessment
* Assessment of toxicity
* Assessment of the impact of mitotane plasma levels and time needed to reach
the therapeutic interval on the efficacy of treatment
* Assessment of the efficacy of the mitotane administration in predefined
subgroups of patients stratified according to:
- type of hormone secretion,
- stage of disease,
- histopathologic characteristics .
Study design
Prospective ,randomized , controlled, open-label, multi-center phase lll trial
Intervention
Patients will be randomly assigned to receive mitotane treatment or
observational follow up only. The daily dose of the drug should be increased if
plasma levels of the mitotane are below 14 mg/l. Reduction of mitotane dosage
should be considered if plasma levels are over 20 mg/l or toxicity does occur.
Mitotane will be administered until progression or unacceptable toxicity for a
minimum of 2 years.
Study burden and risks
The burden and risks associated with participation are constituted by the
possible side effects of mitotane:
- adrenal insufficiency (steroidhormone suppletion starts with mitotane by
default)
- gastro-intestinal disturbances
- liver enzyme alterations
- neurological toxicity
- hormone alterations
Regione Gonzole 10
10043 Orbassano
IT
Regione Gonzole 10
10043 Orbassano
IT
Listed location countries
Age
Inclusion criteria
Histologically confirmed diagnosis of ACC.
Low-intermediate risk of relapse defined as: stage I-III ACC(according to the ENS@T classification 2008).
Microscopically complete resection, defined as no evidence of microscopic residual disease based on surgical reports, histopathology and post-operative imaging.
Ki67 index < or equal 10 %.
Post-operative imaging demonstrating no evidence of disease within 4 weeks before randomization.
ECOG performance status 0-2.
Age equal to or older then 18 years
Adequate bone marrow reserve (neutrophils equal or higher then 1.0 * 10^9/L and/or platelets equal or higher then 80.0 * 10^9/L)
Ability to comply with the protocol procedures
Written informed consent
Exclusion criteria
Time between primary surgery and randomization > 3 months.
Repeated surgery for recurrence of disease.
Renal insufficiency (creatinine clearance <40 ml/min) or liver insufficiency (serum bilirubin >2 times the upper normal range and/ or serum transamininase (AST,ALT)> 3 times the upper normal range).
History of recent or active prior malignancy, except for cured non melanoma skin cancer, cured insitu cervical carinoma, or other treated malignancies where there has been no evidence of disease for at least tree years.
Previous or current treatment with mitotane or other antineoplastic drugs for ACC.
Previous radiotherapy for ACC.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-007262-38-NL |
| ClinicalTrials.gov | NCT00777244 |
| CCMO | NL29842.015.10 |