Efficacy of Adjuvant Mitotane Treatment (ADIUVO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University of Turin, Italy
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
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

Contacts
Contact: Paola Perotti +390119026 ext 643 oncotrial.sanluigi@gmail.com
Contact: Paola Sperone +390119026 ext 017 paola.sperone@email.it

Locations
United States, Maryland
Medical Oncology Branch - Center for Cancer Research - National Cancer Institute Recruiting
Bethesda, Maryland, United States, 20892-1903
Contact: Tito Fojo       fojot@mail.nih.gov   
Contact: Maureen Edgerly    301-435 ext 5604    edgerlym@mail.nih.gov   
Principal Investigator: Tito Fojo         
United States, Michigan
Endocrine Oncology - University of Michigan Comprehensive Cancer Center Active, not recruiting
Ann Arbor, Michigan, United States, 48109-0921
Canada
Endocrinologie - Centre hospitalier de l'Université de Montréal (CHUM) Recruiting
Montreal, Canada, 3840
Contact: André Lacroix       andre.lacroix@umontreal.ca   
Principal Investigator: André Lacroix         
France
Endocrinologie - CHU Besançon Hôpital Jean Minjoz Recruiting
Besancon, France, 25000
Contact: Alfred Perforinis       alfred.penfornis@univ-fcomte.fr   
Contact: Annie Clergeot       aclergeot@chu-besancon.fr   
Principal Investigator: Alfred Penfornis         
Endocrinologie - CHU Lyon Hôpital Pierre Wertheimer Recruiting
Bron, France, 69677
Contact: Michel Pugeat       michel.pugeat@chu-lyon.fr   
Contact: Cecilie Nozieres       cecile.nozieres@chu-lyon.fr   
Principal Investigator: Michel Pugeat         
Endocrinologie - Hôpital A. Michallon Recruiting
La Tronche, France, 38700
Contact: Olivier Cabre    33 04 76 76 ext 5175    OlivierChabre@chu-grenoble.fr   
Principal Investigator: Olivier Cabre         
Endocrinologie - Cochin, APHP Recruiting
Paris, France, 75679
Contact: Bertagna Xavier    +330158 ext 411790    xavier.bertagna@cch.aphp.fr   
Contact: Rossella Libè    +330158 ext 413249    Emrossella.libe@cch.aphp.fr   
Principal Investigator: Xavier Bertagna         
Sub-Investigator: Rossella Libè         
Endocrinologie - CHU Toulouse Hôpital Larrey Recruiting
Toulouse, France
Contact: Philippe Caron       caron.p@chu-toulouse.fr   
Contact: Delphine Vezzosi       vezzosi.d@chu-toulouse.fr   
Principal Investigator: Philippe Caron         
Endocrinologie - Institut de Cancérologie Gustave Roussy Recruiting
Villejuif, France, 94805
Contact: Eric Baudin    +330142 ext 114242    eric.baudin@igr.fr   
Contact: Cécile CHOUGNET    +330142 ext 115224    Cecile.chougnet@igr.fr   
Principal Investigator: Eric Baudin         
Germany
University Hospital Campus Mitte Charitè, Berlin Recruiting
Berlin, Germany, 10117
Contact: Marcus PD Quinkler    030-450 ext 514259    marcus.quinkler@charite.de   
Principal Investigator: Marcus Quinkler, MD         
University Hospital of Dresden Recruiting
Dresden, Germany, 01307
Contact: Stefan Bornstein, MD    0351-458 ext 5955    stefan.bornstein@uniklinikum-dresden.de   
Principal Investigator: Stefan Bornstein, MD         
University Hospital of Düsseldorf Not yet recruiting
Düsseldorf, Germany, 40001
Contact: Holger Willenberg, MD       Holger.Willenberg@uni-duesseldorf.de   
Principal Investigator: Holger Willenberg         
Center for Endocrine Tumors - ENDOC Recruiting
Hamburg, Germany, 20357
Contact: Stephan Petersenn, MD    040-401 ext 87985    stephan.petersenn@endoc-med.de   
Principal Investigator: Stephan Petersenn         
University Medicin Centre of Munchen Recruiting
München, Germany, 80336
Contact: Felix Beuschlein, MD    089 -5160 ext 2110    felix.beuschlein@med.uni-muenchen.de   
Contact: Martin Fassnacht       Fassnacht_m@medizin.uni-wuerzburg.de   
Principal Investigator: Felix Beuschlein         
University Hospital Wuerzburg, Endocrinology Recruiting
Wurzburg, Germany, 97080
Contact: Martin MD Fassnacht    0931-201- ext 39021    Fassnacht_M@medizin.uni-wuerzburg.de   
Contact: Patricia Sculler       Schuller_P@medizin.uni-wuerzburg.de   
Principal Investigator: Martin Fassnacht, MD         
Italy
A.O.Universitaria Arcispedale S.Anna Ferrara Recruiting
Ferrara, Fe, Italy, 44100
Contact: Prof. Ettore Degli Uberti         
Principal Investigator: Ettore Degli Uberti         
UO Oncologia Medica - AO Spedali Civili Recruiting
Brescia, Italy, 25123
Contact: Alfredo Berruti       alfredo.berruti@gmail.com   
Contact: Anna Scalvini       annascalvini@gmail.com   
Principal Investigator: Alfredo Berruti         
Università degli studi di Firenze Not yet recruiting
Firenze, Italy
Contact: Massimo Mannelli         
Sub-Investigator: Massimo Mannelli         
Azienda Ospedaliera di Foggia Active, not recruiting
Foggia, Italy
Ospedale Cà Granda-Niguarda-Milano Recruiting
Milano, Italy
Contact: Paola Loli         
Sub-Investigator: Paola Loli         
Azienda Ospedaliera San Luigi Recruiting
Orbassano, Italy, 10043
Contact: Paola Perotti    +390119026 ext 017    oncotrial.sanluigi@gmail.com   
Department of Clinical and Biological Sciences, University of Turin, Internal Medicine 1 Recruiting
Orbassano, Italy, 10043
Contact: Paola Perotti    +390119026 ext 513    oncotrial.sanluigi@gmail.com   
Principal Investigator: Massimo Terzolo, MD         
Azienda Ospedaliera Padova Active, not recruiting
Padova, Italy
Università degli studi di Palermo Not yet recruiting
Palermo, Italy
Contact: Vittorio Gebbia         
Policlinico Universitario A. Gemelli Active, not recruiting
Roma, Italy
A.O.U. San Giovanni Battista - Molinette Recruiting
Torino, Italy
Contact: Enzo Gigo, MD         
Principal Investigator: Enzo Ghigo         
Netherlands
Dept. of Internal Medicine Maxima Medisch Centrum Recruiting
Eindhoven, Netherlands, 5600 PD
Principal Investigator: Harm Haak, MD         
United Kingdom
Cancer Research UK Clinical Trials Unit (CRCTU) - School of Cancer Sciences - University of Birmingham Not yet recruiting
Birmingham, Edgbaston, United Kingdom, 152TT
Contact: Wiebke Arlt       w.arlt@bham.ac.uk   
Contact: Ana Huges       a.i.hughes@bham.ac.uk   
Principal Investigator: Wiebke Arlt         
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

Additional 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:
Adrenocortical Carcinoma
Carcinoma
Adenocarcinoma
Adrenal Cortex Diseases
Adrenal Cortex Neoplasms
Adrenal Gland Diseases
Adrenal Gland Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Mitotane
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014