Efficacy of Adjuvant Mitotane Treatment (ADIUVO)

Adrenocortical Carcinoma Clinical Trial

— ADIUVO  

Official title:

Efficacy of Adjuvant Mitotane Treatment in Prolonging Recurrence-free Survival in Patients With Adrenocortical Carcinoma at Low-intermediate Risk of Recurrence

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00777244
• Other study ID #: EudraCT 2007-007262-38
• Status: Recruiting
• Phase: Phase 3
• First received: October 21, 2008
• Last updated: May 4, 2017
• Start date: April 2008
• Est. completion date: December 2020

Study information

• Verified date: May 2017
• Source: University of Turin, Italy
• Contact: Paola Perotti
• Phone: +390119026
• Email: oncotrial.sanluigi[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2020
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adrenocortical Carcinoma
• Carcinoma

Intervention

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.

Locations

Country	Name	City	State
Canada	Endocrinologie - Centre hospitalier de l'Université de Montréal (CHUM)	Montreal
France	Endocrinologie - CHU Besançon Hôpital Jean Minjoz	Besancon
France	Endocrinologie - CHU Lyon Hôpital Pierre Wertheimer	Bron
France	Endocrinologie - Hôpital A. Michallon	La Tronche
France	Endocrinologie - Cochin, APHP	Paris
France	Endocrinologie - CHU Toulouse Hôpital Larrey	Toulouse
France	Endocrinologie - Institut de Cancérologie Gustave Roussy	Villejuif
Germany	University Hospital Campus Mitte Charitè, Berlin	Berlin
Germany	University Hospital of Dresden	Dresden
Germany	University Hospital of Düsseldorf	Düsseldorf
Germany	Center for Endocrine Tumors - ENDOC	Hamburg
Germany	University Medicin Centre of Munchen	München
Germany	University Hospital Wuerzburg, Endocrinology	Wurzburg
Italy	UO Oncologia Medica - AO Spedali Civili	Brescia
Italy	A.O.Universitaria Arcispedale S.Anna Ferrara	Ferrara	Fe
Italy	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	Department of Clinical and Biological Sciences, University of Turin, Internal Medicine 1	Orbassano
Italy	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
Netherlands	Dept. of Internal Medicine Maxima Medisch Centrum	Eindhoven
United Kingdom	Cancer Research UK Clinical Trials Unit (CRCTU) - School of Cancer Sciences - University of Birmingham	Birmingham	Edgbaston
United States	Endocrine Oncology - University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Medical Oncology Branch - Center for Cancer Research - National Cancer Institute	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
University of Turin, Italy

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Netherlands,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Free survival	Survival in years	Till the last follow up

External Links

•   study website