Mitotane With or Without Cisplatin and Etoposide After Surgery in Treating Patients With Stage I-III Adrenocortical Cancer With High Risk of Recurrence
A Randomized Registry Trial of Adjuvant Mitotane vs. Mitotane With Cisplatin/Etoposide After Primary Surgical Resection of Localized Adrenocortical Carcinoma With High Risk of Recurrence (ADIUVO-2 Trial)
2 other identifiers
interventional
240
4 countries
25
Brief Summary
This phase III trial studies how well mitotane alone works compared to mitotane with cisplatin and etoposide when given after surgery in treating patients with adrenocortical cancer that has a high risk of coming back (recurrence). Cortisol can cause the growth of adrenocortical tumor cells. Antihormone therapy, such as mitotane, may lessen the amount of cortisol made by the body. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether mitotane alone or mitotane with cisplatin and etoposide after surgery works better in treating patients with adrenocortical carcinoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2018
Longer than P75 for phase_3
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 28, 2018
CompletedFirst Posted
Study publicly available on registry
July 11, 2018
CompletedStudy Start
First participant enrolled
August 20, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2029
January 30, 2026
January 1, 2026
10.4 years
June 28, 2018
January 28, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Recurrence-free survival (RFS)
Starting from the date of randomization until documentation of radiological evidence of local recurrence, radiological evidence of distant recurrence, or death from any cause (whichever occurs first), RFS will be compared using the log-rank test between the two arms.
From the time of randomization up to 2 years
Local recurrence of adrenocortical carcinoma (ACC)
Up to 6 months
Distant recurrence of ACC
Up to 6 months
Secondary Outcomes (1)
Overall survival (OS)
From the time of randomization up to 2 years
Study Arms (2)
Arm A (mitotane)
EXPERIMENTALPatients receive mitotane PO daily on days 1-21. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.
Arm B (mitotane, etoposide, cisplatin)
EXPERIMENTALPatients receive mitotane as in Arm A. Patients also receive cisplatin IV over 2 hours on day 1 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Ancillary studies
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- Have a histologically confirmed diagnosis of ACC (Weiss score of \>= 3). (LinWeiss-Bisceglia system will be used for oncocytic ACC).
- Have a high risk of relapse defined as: Stage I-III ACC (according to the European Network for the Study of Adrenal Tumors \[ENSAT\] classification) within 90 days of surgical resection of primary tumor with curative intent with either microscopically complete resection (R0, defined as no evidence of microscopic residual disease according to surgical reports, histopathology, and perioperative imaging), microscopically positive margins (R1), or undetermined margins (RX, based on surgical or pathological reports without unequivocal evidence of metastasis in the perioperative imaging). Each participating center will determine the pathological stages and resection margins AND Ki67 \> 10% (to be determined by an experienced pathologist in each participating center and preferably via quantitative imaging analysis).
- Have perioperative imaging (computed tomography \[CT\] with contrast, magnetic resonance imaging \[MRI\] of the chest/abdomen/pelvis, or fluorodeoxyglucose positron emission tomography \[FDG-PET\] CT) without unequivocal evidence of disease within 8 weeks before randomization. Patients with indeterminate non-specific nodules (\< 1 cm for soft tissue lesions and \< 1.5 cm in the short dimension for lymph nodes) will be permitted to participate in this study.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Be able to comply with the protocol procedures.
- Provide written informed consent.
You may not qualify if:
- The time between primary surgery and randomization \> 90 days.
- Gross residual disease after surgery (R2 resection)
- High suspicion for metastatic disease on perioperative imaging
- They have undergone repeated surgery for recurrence of disease.
- They have a history of recent or active prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, breast ductal carcinoma in situ, or other treated malignancies where there has been no evidence of disease for at least 2 years.
- They have renal insufficiency (estimated glomerular filtration rate \[GFR\] \< 50 mL/min/1.73 m\^2).
- They have significant liver insufficiency (serum bilirubin \> 2 times the upper normal range)
- They have significant liver insufficiency (serum alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] \> 3 times the upper normal range)
- Impaired bone marrow reserve (neutrophils \< 1000/mm\^3)
- Impaired bone marrow reserve (platelets \< 100,000/mm\^3)
- Pregnancy or breast feeding.
- They have known congestive heart failure (ejection fraction \< 45%). The extent of cardiac testing will depend on the judgment of the local principal investigator (PI). In general, in patients with a history of cardiac disease, it is recommended to obtain a baseline two-dimensional echocardiogram as standard of care to document ejection fraction. In patients without prior cardiac disease, a baseline electrocardiogram (EKG) is sufficient if there is no evidence of acute ischemic changes or prior evidence of myocardial infarction. If EKG results are abnormal (ischemic changes, significant arrhythmia, or suggestion of prior myocardial infarction), a two-dimensional echocardiogram will be obtained to assess ejection fraction. Cardiac imaging and EKG may not be needed in patients assigned to mitotane who do not have prior cardiac history and have low suspicion for cardiac symptoms to reflect standards of clinical practice. Similarly, utilizing cardiac imaging and EKG within the past 12 months is permitted if there is no suspicion for cardiac issues.
- They have preexisting grade 2 peripheral neuropathy.
- They underwent previous or current treatment with mitotane or other antineoplastic drugs for ACC.
- They underwent previous radiotherapy for ACC.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)collaborator
- M.D. Anderson Cancer Centerlead
Study Sites (25)
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Siteman Cancer Center at Washington University
St Louis, Missouri, 63110, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Institut de Cancérologie de l'Ouest (ICO)
Angers, 49055, France
CHU Angers, Hôpital Larrey
Angers, 49933, France
CHU Besançon, Hôpital Jean Minjoz
Besançon, 25000, France
CHU Brest, Hôpital La Cavale Blanche
Brest, 29200, France
Centre Georges François Leclerc
Dijon, 25000, France
HCL Hôpital Louis Pradel
Lyon, 69877, France
CHU Nantes, Hôpital René et Guillaume Laënnec
Nantes, 44093, France
CHU Nantes, Hôpital René et Guillaume Laënnec
Nantes, 44093, France
Hôpital Cochin, AP-HP
Paris, 75014, France
Hôpital Cochin, AP-HP
Paris, 75014, France
CHU Bordeaux - Hôpital Haut Lévèque
Pessac, 33600, France
CHU Poitiers
Poitiers, 86000, France
CHU Reims
Reims, 51092, France
HUS, Hôpital Hautepierre
Strasbourg, 67000, France
ICANS Institut de cancérologie Strasbourg Europe
Strasbourg, 67200, France
CHU Toulouse, Hôpital Larrey
Toulouse, 31059, France
CHU Toulouse, Hôpital Rangueil
Toulouse, 31400, France
Gustave Roussy
Villejuif, 94805, France
Maria Sklodowska-Curie National Research Institute of Oncology
Gliwice, 44-102, Poland
Sahlgrenska University Hospital
Gothenburg, Sweden
Karolinska University Hospital
Stockholm, Sweden
Akademiska Sjukhuset
Uppsala, Sweden
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jeena Varghese
M.D. Anderson Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 28, 2018
First Posted
July 11, 2018
Study Start
August 20, 2018
Primary Completion (Estimated)
January 1, 2029
Study Completion (Estimated)
January 1, 2029
Last Updated
January 30, 2026
Record last verified: 2026-01