Efficacy of Adjuvant Mitotane Treatment (ADIUVO)

NCT ID: NCT00777244

Last Updated: 2017-05-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-04-30

Study Completion Date

2020-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Adrenocortical Carcinoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Follow-up

Arm B

Group Type NO_INTERVENTION

No interventions assigned to this group

Mitotane

Arm A

Group Type EXPERIMENTAL

MITOTANE

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Mitotane (Lysodren)

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Turin, Italy

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Alfredo Berruti

Prof.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Massimo Terzolo, MD

Role: STUDY_CHAIR

Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Italy

Martin Fassnacht, MD

Role: STUDY_DIRECTOR

Department of Internal Medicine, University of Wuerzburg, Germany

Alfredo Berruti, MD

Role: STUDY_CHAIR

Medical Oncology, Department of Clinical and Biological Sciences, University of Turin

Eric Baudin, MD

Role: PRINCIPAL_INVESTIGATOR

Oncologie Endocrinienne et Médecine Nucléaire, Institut Gustave Roussy, Villejuif, France.

Harm Haak, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Internal Medicine, Máxima Medical Centre, Eindhoven, The Netherlands

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Medical Oncology Branch - Center for Cancer Research - National Cancer Institute

Bethesda, Maryland, United States

Site Status RECRUITING

Endocrine Oncology - University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status ACTIVE_NOT_RECRUITING

Endocrinologie - Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, , Canada

Site Status RECRUITING

Endocrinologie - CHU Besançon Hôpital Jean Minjoz

Besançon, , France

Site Status RECRUITING

Endocrinologie - CHU Lyon Hôpital Pierre Wertheimer

Bron, , France

Site Status RECRUITING

Endocrinologie - Hôpital A. Michallon

La Tronche, , France

Site Status RECRUITING

Endocrinologie - Cochin, APHP

Paris, , France

Site Status RECRUITING

Endocrinologie - CHU Toulouse Hôpital Larrey

Toulouse, , France

Site Status RECRUITING

Endocrinologie - Institut de Cancérologie Gustave Roussy

Villejuif, , France

Site Status RECRUITING

University Hospital Campus Mitte Charitè, Berlin

Berlin, , Germany

Site Status RECRUITING

University Hospital of Dresden

Dresden, , Germany

Site Status RECRUITING

University Hospital of Düsseldorf

Düsseldorf, , Germany

Site Status NOT_YET_RECRUITING

Center for Endocrine Tumors - ENDOC

Hamburg, , Germany

Site Status RECRUITING

University Medicin Centre of Munchen

München, , Germany

Site Status RECRUITING

University Hospital Wuerzburg, Endocrinology

Würzburg, , Germany

Site Status RECRUITING

A.O.Universitaria Arcispedale S.Anna Ferrara

Ferrara, Fe, Italy

Site Status RECRUITING

UO Oncologia Medica - AO Spedali Civili

Brescia, , Italy

Site Status RECRUITING

Università degli studi di Firenze

Florence, , Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliera di Foggia

Foggia, , Italy

Site Status ACTIVE_NOT_RECRUITING

Ospedale Cà Granda-Niguarda-Milano

Milan, , Italy

Site Status RECRUITING

Azienda Ospedaliera San Luigi

Orbassano, , Italy

Site Status RECRUITING

Department of Clinical and Biological Sciences, University of Turin, Internal Medicine 1

Orbassano, , Italy

Site Status RECRUITING

Azienda Ospedaliera Padova

Padua, , Italy

Site Status ACTIVE_NOT_RECRUITING

Università degli studi di Palermo

Palermo, , Italy

Site Status NOT_YET_RECRUITING

Policlinico Universitario A. Gemelli

Roma, , Italy

Site Status ACTIVE_NOT_RECRUITING

A.O.U. San Giovanni Battista - Molinette

Torino, , Italy

Site Status RECRUITING

Dept. of Internal Medicine Maxima Medisch Centrum

Eindhoven, , Netherlands

Site Status RECRUITING

Cancer Research UK Clinical Trials Unit (CRCTU) - School of Cancer Sciences - University of Birmingham

Birmingham, Edgbaston, United Kingdom

Site Status NOT_YET_RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States Canada France Germany Italy Netherlands United Kingdom

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Paola Perotti

Role: CONTACT

+390119026 ext. 643

Paola Sperone

Role: CONTACT

+390119026 ext. 017

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Tito Fojo

Role: primary

Maureen Edgerly

Role: backup

301-435 ext. 5604

André Lacroix

Role: primary

Alfred Perforinis

Role: primary

Annie Clergeot

Role: backup

Michel Pugeat

Role: primary

Cecilie Nozieres

Role: backup

Olivier Cabre

Role: primary

33 04 76 76 ext. 5175

Bertagna Xavier

Role: primary

+330158 ext. 411790

Rossella Libè

Role: backup

+330158 ext. 413249

Philippe Caron

Role: primary

Delphine Vezzosi

Role: backup

Eric Baudin

Role: primary

+330142 ext. 114242

Cécile CHOUGNET

Role: backup

+330142 ext. 115224

Marcus PD Quinkler

Role: primary

030-450 ext. 514259

Stefan Bornstein, MD

Role: primary

0351-458 ext. 5955

Holger Willenberg, MD

Role: primary

Stephan Petersenn, MD

Role: primary

040-401 ext. 87985

Felix Beuschlein, MD

Role: primary

089 -5160 ext. 2110

Martin Fassnacht

Role: backup

Martin MD Fassnacht

Role: primary

0931-201- ext. 39021

Patricia Sculler

Role: backup

Prof. Ettore Degli Uberti

Role: primary

Alfredo Berruti

Role: primary

Anna Scalvini

Role: backup

Massimo Mannelli

Role: primary

Paola Loli

Role: primary

Paola Perotti

Role: primary

+390119026 ext. 017

Paola Perotti

Role: primary

+390119026 ext. 513

Vittorio Gebbia

Role: primary

Enzo Gigo, MD

Role: primary

Wiebke Arlt

Role: primary

Ana Huges

Role: backup

References

Explore related publications, articles, or registry entries linked to this study.

Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, Rossetto R, Buci L, Sperone P, Grossrubatscher E, Reimondo G, Bollito E, Papotti M, Saeger W, Hahner S, Koschker AC, Arvat E, Ambrosi B, Loli P, Lombardi G, Mannelli M, Bruzzi P, Mantero F, Allolio B, Dogliotti L, Berruti A. Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med. 2007 Jun 7;356(23):2372-80. doi: 10.1056/NEJMoa063360.

Reference Type BACKGROUND
PMID: 17554118 (View on PubMed)

Terzolo M, Fassnacht M, Perotti P, Libe R, Kastelan D, Lacroix A, Arlt W, Haak HR, Loli P, Decoudier B, Lasolle H, Quinkler M, Haissaguerre M, Chabre O, Caron P, Stigliano A, Giordano R, Zatelli MC, Bancos I, Fragoso MCBV, Canu L, Luconi M, Puglisi S, Basile V, Reimondo G, Kroiss M, Megerle F, Hahner S, Kimpel O, Dusek T, Nolting S, Bourdeau I, Chortis V, Ettaieb MH, Cosentini D, Grisanti S, Baudin E, Berchialla P, Bovis F, Sormani MP, Bruzzi P, Beuschlein F, Bertherat J, Berruti A. Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study. Lancet Diabetes Endocrinol. 2023 Oct;11(10):720-730. doi: 10.1016/S2213-8587(23)00193-6. Epub 2023 Aug 21.

Reference Type DERIVED
PMID: 37619579 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

EudraCT 2007-007262-38

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

ACT-TIL and ANV419 for Advanced Melanoma.
NCT05869539 ACTIVE_NOT_RECRUITING PHASE1