Efficacy of Adjuvant Mitotane Treatment (ADIUVO) (ADIUVO)
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ClinicalTrials.gov Identifier: NCT00777244 |
Recruitment Status
:
Recruiting
First Posted
: October 22, 2008
Last Update Posted
: May 8, 2017
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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 or disease | Intervention/treatment | Phase |
---|---|---|
Adrenocortical Carcinoma | Drug: MITOTANE | Phase 3 |
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 Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 200 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (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 |
Study Start Date : | April 2008 |
Estimated Primary Completion Date : | December 2018 |
Estimated Study Completion Date : | December 2020 |

Arm | Intervention/treatment |
---|---|
No Intervention: Follow-up
Arm B
|
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Experimental: Mitotane
Arm A
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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)
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- Disease Free survival [ Time Frame: Till the last follow up ]Survival in years

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00777244
Contact: Paola Perotti | +390119026 ext 643 | oncotrial.sanluigi@gmail.com | |
Contact: Paola Sperone | +390119026 ext 017 | paola.sperone@email.it |
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 |
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 |
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 |
First Posted: | October 22, 2008 Key Record Dates |
Last Update Posted: | May 8, 2017 |
Last Verified: | May 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Keywords provided by Alfredo Berruti, University of Turin, Italy:
mitotane adjuvant therapy disease free survival |
Additional relevant MeSH terms:
Adrenal Gland Neoplasms Carcinoma Adrenocortical Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Adrenal Cortex Neoplasms |
Endocrine Gland Neoplasms Neoplasms by Site Adrenal Cortex Diseases Adrenal Gland Diseases Endocrine System Diseases Mitotane Antineoplastic Agents, Hormonal Antineoplastic Agents |