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Efficacy of Adjuvant Mitotane Treatment (ADIUVO) (ADIUVO)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified November 2013 by University of Turin, Italy.
Recruitment status was:  Recruiting
Sponsor:
Information provided by (Responsible Party):
Alfredo Berruti, University of Turin, Italy
ClinicalTrials.gov Identifier:
NCT00777244
First received: October 21, 2008
Last updated: November 8, 2013
Last verified: November 2013
  Purpose

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


Condition Intervention Phase
Adrenocortical Carcinoma
Drug: MITOTANE
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy of Adjuvant Mitotane Treatment in Prolonging Recurrence-free Survival in Patients With Adrenocortical Carcinoma at Low-intermediate Risk of Recurrence

Resource links provided by NLM:


Further study details as provided by University of Turin, Italy:

Primary Outcome Measures:
  • Disease Free survival [ Time Frame: six years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: April 2008
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Follow-up
Patients enrolled will undergo strict follow-up
Experimental: Mitotane Drug: MITOTANE
mitotane will be administered at a starting dose of 1.5 g/day and increased in case of good gastrointestinal tolerance on day 2 to 3 g/day, on day 3 to 4.5 g/day, and on day 4 to 6 g/day. A dose of 6 g/day will be administered until first mitotane blood level is assessed. Further adjustment of dosage will be performed according to blood concentrations and tolerability.
Other Name: Mitotane (Lysodren)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00777244

Locations
United States, Maryland
Medical Oncology Branch - Center for Cancer Research - National Cancer Institute
Bethesda, Maryland, United States, 20892-1903
United States, Michigan
Endocrine Oncology - University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0921
Canada
Endocrinologie - Centre hospitalier de l'Université de Montréal (CHUM)
Montreal, Canada, 3840
France
Endocrinologie - CHU Besançon Hôpital Jean Minjoz
Besancon, France, 25000
Endocrinologie - CHU Lyon Hôpital Pierre Wertheimer
Bron, France, 69677
Endocrinologie - Hôpital A. Michallon
La Tronche, France, 38700
Endocrinologie - Cochin, APHP
Paris, France, 75679
Endocrinologie - CHU Toulouse Hôpital Larrey
Toulouse, France
Endocrinologie - Institut de Cancérologie Gustave Roussy
Villejuif, France, 94805
Germany
University Hospital Campus Mitte Charitè, Berlin
Berlin, Germany, 10117
University Hospital of Dresden
Dresden, Germany, 01307
University Hospital of Düsseldorf
Düsseldorf, Germany, 40001
Center for Endocrine Tumors - ENDOC
Hamburg, Germany, 20357
University Medicin Centre of Munchen
München, Germany, 80336
University Hospital Wuerzburg, Endocrinology
Wurzburg, Germany, 97080
Italy
A.O.Universitaria Arcispedale S.Anna Ferrara
Ferrara, Fe, Italy, 44100
UO Oncologia Medica - AO Spedali Civili
Brescia, Italy, 25123
Università degli studi di Firenze
Firenze, Italy
Azienda Ospedaliera di Foggia
Foggia, Italy
Ospedale Cà Granda-Niguarda-Milano
Milano, Italy
Azienda Ospedaliera San Luigi
Orbassano, Italy, 10043
Department of Clinical and Biological Sciences, University of Turin, Internal Medicine 1
Orbassano, Italy, 10043
Azienda Ospedaliera Padova
Padova, Italy
Università degli studi di Palermo
Palermo, Italy
Policlinico Universitario A. Gemelli
Roma, Italy
A.O.U. San Giovanni Battista - Molinette
Torino, Italy
Netherlands
Dept. of Internal Medicine Maxima Medisch Centrum
Eindhoven, Netherlands, 5600 PD
United Kingdom
Cancer Research UK Clinical Trials Unit (CRCTU) - School of Cancer Sciences - University of Birmingham
Birmingham, Edgbaston, United Kingdom, 152TT
Sponsors and Collaborators
University of Turin, Italy
Investigators
Study Chair: Massimo Terzolo, MD Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Italy
Study Director: Martin Fassnacht, MD Department of Internal Medicine, University of Wuerzburg, Germany
Study Chair: Alfredo Berruti, MD Medical Oncology, Department of Clinical and Biological Sciences, University of Turin
Principal Investigator: Eric Baudin, MD Oncologie Endocrinienne et Médecine Nucléaire, Institut Gustave Roussy, Villejuif, France.
Principal Investigator: Harm Haak, MD Department of Internal Medicine, Máxima Medical Centre, Eindhoven, The Netherlands
  More Information

Publications:
Responsible Party: Alfredo Berruti, Prof., University of Turin, Italy
ClinicalTrials.gov Identifier: NCT00777244     History of Changes
Other Study ID Numbers: EudraCT 2007-007262-38 
Study First Received: October 21, 2008
Last Updated: November 8, 2013
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University of Turin, Italy:
mitotane
adjuvant therapy
disease free survival

Additional relevant MeSH terms:
Carcinoma
Adrenocortical Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Adrenal Cortex Neoplasms
Adrenal Gland Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Adrenal Cortex Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Mitotane
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on December 02, 2016