Efficacy of Adjuvant Mitotane Treatment (ADIUVO)

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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