Recruiting
Phase 3

Mitotane

Sponsor:

University of Turin, Italy

Code:

NCT00777244

Conditions

Adrenocortical Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

MITOTANE

Study Details

Brief 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

Conditions

Adrenocortical Carcinoma

Study ID

NCT00777244

Start date

Apr, 2008

Status verified date

May, 2017

Completion date

Dec, 2020

Anticipated

Primary completion date

Dec, 2018

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not 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.

Study Design

Enrollment

200 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

no intervention: Follow-up

Arm B

experimental: Mitotane

Arm A

Interventions

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.

Primary outcome measure

  • Disease Free survival [ Time Frame: Till the last follow up ]

Central Contacts and Locations

Central contacts

Paola Perotti

+390119026oncotrial.sanluigi@gmail.com

Paola Sperone

+390119026paola.sperone@email.it

Locations

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

Recruiting

Bethesda, Maryland, United States, 20892-1903

Contacts

Tito Fojo

fojot@mail.nih.gov

Maureen Edgerly

301-435edgerlym@mail.nih.gov

Principal Investigator:

Tito Fojo

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

Recruiting

Montreal, Canada, 3840

Contacts

André Lacroix

andre.lacroix@umontreal.ca

Principal Investigator:

André Lacroix

More Information

Sponsor

University of Turin, Italy

Last update posted

May 8, 2017

Last verified

May, 2017

Keywords

  • mitotane
  • adjuvant therapy
  • disease free survival

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Turin, Italy on 2017-05-08.