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ENSAT Stage I Adrenal Cortex CarcinomaPhase 3NCT03583710

Mitotane With or Without Cisplatin and Etoposide After Surgery in Treating Patients With Stage I-III Adrenocortical Cancer With High Risk of Recurrence

A Phase 3 study testing Cisplatin, Etoposide and Mitotane in people with ENSAT Stage I Adrenal Cortex Carcinoma and ENSAT Stage II Adrenal Cortex Carcinoma, run by M.D. Anderson Cancer Center at 33 sites in 5 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cisplatin, Etoposide and Mitotane
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
240 participants
Where
33 sitesin 5 countries
Study dates
20 Aug 2018to 1 Jan 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
Show all 16Show fewer
  • 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.
  • They have any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would, in the judgment of the investigator, pose excess risk associated with study participation or administration of the involved drugs or that, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Trial locations and contacts

33 sites in 5 countries. Contact the study team or a site near you to ask about taking part.

Jeena Varghese contact

713-792-2841

jvarghese@mdanderson.org

33 sites in 5 countries

France23 sites, 16 recruiting

  • Institut de Cancérologie de l'Ouest (ICO)

    Angers, 49055

    Active, not recruiting

  • CHU Angers, Hôpital Larrey

    Angers, 49933

    Sandrine Laboureau, MD, +33 2 41.35.45.93, salaboureau@chu-angers.fr

    Sandrine Laboureau, MD

    Recruiting

  • CHU Besançon, Hôpital Jean Minjoz

    Besançon, 25000

    Emmanuel N'Guyen, MD, +33 3 70 63 24 03, doctnguyen@hotmail.com

    Emmanuel N'Guyen, MD

    Recruiting

  • CHU Brest, Hôpital La Cavale Blanche

    Brest, 29200

    Active, not recruiting

  • Centre Georges François Leclerc

    Dijon, 25000

    Sylvie Zanetta, MD, +33 3.80.73.75.06, szanetta@cgfl.fr

    Sylvie Zanetta, MD

    Recruiting

  • Lyon HCL

    Lyon, 69002

    Hélène Lasolle, MD, 04.27.85.66.66, Helene.lasolle@chu-lyon.fr

    Hélène Lasolle, MD

    Recruiting

  • HCL Hôpital Louis Pradel

    Lyon, 69877

    Hélène Lasolle, MD, +33 4.27.85.66.66, Helene.lasolle@chu-lyon.fr

    Hélène Lasolle, MD

    Not yet recruiting

  • Marseille Hôpital Nord

    Marseille, 13015

    Marie-Eve Garcia, MD, 04.91.96.59.01, marie-eve.garcia@ap-hm.fr

    Marie-Eve Garcia, MD

    Recruiting

  • Marseille Hôpital de la Conception

    Marseille

    Pr Fréderic Castinetti, MD, 04.91.38.34.79, Frederic.castinetti@ap-hm.fr

    Pr Fréderic Castinetti, MD

    Recruiting

  • CHU Nantes, Hôpital René et Guillaume Laënnec

    Nantes, 44093

    Active, not recruiting

  • CHU Nantes, Hôpital René et Guillaume Laënnec

    Nantes, 44093

    Alexandre Lugat, MD, +33 2 40 16 56 30, alexandre.lugat@chu-nantes.fr

    Alexandre Lugat, MD

    Recruiting

  • Hôpital Cochin, AP-HP

    Paris, 75014

    Rossella Libé, MD, +33 1 58 41 32 49, rossella.libe@aphp.fr

    Rossella Libé, MD

    Recruiting

  • Hôpital Cochin, AP-HP

    Paris, 75014

    Active, not recruiting

  • Hôpital Cochin

    Paris, 75014

    Rossella LIBÉ, MD, 01 58 41 32 49, Rossella.libe@aphp.fr

    Rossella LIBÉ LIBÉ, MD

    Recruiting

  • Hôpital COCHIN

    Paris, 75014

    Active, not recruiting

  • CHU Bordeaux - Hôpital Haut Lévèque

    Pessac, 33600

    Magalie Haissaguerre, MD, +33 5.57.65.60.78, magalie.haissaguerre@chu-bordeaux.fr

    Magalie Haissaguerre, MD

    Recruiting

  • CHU Poitiers

    Poitiers, 86000

    Aurélie Miot, MD, +33 5.49.44.40.34, aurelie.miot@chu-poitiers.fr

    Aurélie Miot, MD

    Recruiting

  • CHU Reims

    Reims, 51092

    Bénédicte Decoudier, MD, +33 3 26 78 71 56, bdecoudier@chu-reims.fr

    Bénédicte Decoudier, MD

    Recruiting

  • HUS, Hôpital Hautepierre

    Strasbourg, 67000

    Philippe Baltzinger, MD, +33 3.88.12.76.40, philippe.baltzinger@chru-strasbourg.fr

    Philippe Baltzinger, MD

    Not yet recruiting

  • Strasbourg HUS Hautepierre

    Strasbourg, 67000

    Active, not recruiting

  • CHU Toulouse, Hôpital Larrey

    Toulouse, 31059

    Delphine Vezzosi, MD, +33 5.67.77.17.01, vezzosi.d@chu-toulouse.fr

    Delphine Vezzosi, MD

    Recruiting

  • CHU Toulouse, Hôpital Rangueil

    Toulouse, 31400

    Active, not recruiting

  • Gustave Roussy

    Villejuif, 94805

    Eric Baudin, MD, +33 1 42 11 42 42, Eric.baudin@gustaveroussy.fr

    Eric Baudin, MD

    Recruiting

Other trials in France

Sweden4 sites, 4 recruiting

  • Sahlgrenska University Hospital

    Gothenburg

    Andreas Hallqvist, +46313421000, andreas.hallqvist@vgregion.se

    Andreas Hallqvist

    Recruiting

  • Skånes Universitetssjukhus

    Lund

    Carl Fredrik Warfvinge, MD, carl_fredrik.warfvinge@med.lu.se

    Carl Fredrik Warfvinge, MD

    Recruiting

  • Karolinska University Hospital

    Stockholm

    David Goldstein, +46 8 123 70 000, david.goldstein@regionstockholm.se

    David Goldstein

    Recruiting

  • Akademiska Sjukhuset

    Uppsala

    +46186110000, Joakim.crona@akademiska.se

    Joakim Crona

    Recruiting

Other trials in Sweden

United States3 sites, 2 recruiting

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

    Francis P. Worden, fworden@umich.edu

    Francis P. Worden

    Recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Jeena Varghese, 713-792-2841, jvarghese@mdanderson.org

    Jeena Varghese

    Recruiting

  • Siteman Cancer Center at Washington University

    St Louis, Missouri, 63110

    Active, not recruiting

Other trials in United States

Germany2 sites, 2 recruiting

  • LMU Klinikum München

    Munich, 80336

    Nicole Reisch, MD, +49 89 4400 52110, Nicole.Reisch@med.uni-muenchen.de

    Nicole Reisch, MD

    Recruiting

  • Universitätsklinikum Würzburg

    Würzburg, 97080

    Martin Fassnacht, MD, +49 931 201 39200, Fassnacht_M@ukw.de

    Martin Fassnacht, MD

    Recruiting

Other trials in Germany

Poland1 site

  • Maria Sklodowska-Curie National Research Institute of Oncology

    Gliwice, 44-102

    Active, not recruiting

Other trials in Poland

About this study

Official title: 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)

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare the effect of adjuvant mitotane treatment alone (arm A) with that of adjuvant mitotane combined with four 21-day cycles of etoposide/cisplatin (arm B) on recurrence-free survival (RFS) in patients with high-risk adrenocortical carcinoma (ACC) after initial surgical resection.

SECONDARY OBJECTIVES:

  1. Assess overall survival (OS), defined as the time interval between the date of randomization and the date of death from any cause.

II. Assess the effect of serum mitotane levels, disease stage, and surgical resection margins on clinical outcomes.

III. Assess the effect of early start (1-6 weeks from surgery) versus (vs.) late start (> 6 weeks from surgery) of adjuvant therapy on clinical outcomes.

IV. Assess serious adverse events. V. Measure quality of life at baseline, 6 weeks, 6 months after the initiation of adjuvant therapy, and at the end of study participation (recurrence or completing study treatments) using a validated quality of life questionnaire (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30).

EXPLORATORY OBJECTIVES:

  1. Perform molecular profiling on available tissue specimens obtained at the time of initial surgical resection (formalin-fixed paraffin-embedded or frozen tissues) to identify genomic alterations in primary tumors that are associated with the clinical end points.

II. Evaluate markers to detect ACC recurrence or predict response to therapy (including steroid hormones and precursors, circulating tumor cells, and micro ribonucleic acid [microRNA]).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive mitotane orally (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: Patients receive mitotane as in Arm A. Patients also receive cisplatin intravenously (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.

After completion of study treatment, patients are followed up every 6 months.

Being tested
Cisplatin, Etoposide, Mitotane, Quality-of-Life Assessment

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • MitotaneDrug

    Also called (o,p)-DDD, 1, 1-Dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane, 1-Chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene, 2, 2-Bis(2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane

    Given PO

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT03583710
Study groupRoleWhat they receive
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.
Receives: Drug: Mitotane; Other: Quality-of-Life Assessment
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.
Receives: Drug: Cisplatin; Drug: Etoposide; Drug: Mitotane; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From the time of randomization up to 2 years

  2. Local recurrence of adrenocortical carcinoma (ACC)

    Measured: Up to 6 months

  3. Distant recurrence of ACC

    Measured: Up to 6 months

Secondary outcomes (1)

  1. Overall survival (OS)

    Overall survival will be compared using the log-rank test.

    Measured: From the time of randomization up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2018
  2. Study start20 Aug 2018
  3. Primary completion1 Jan 2029 (estimated)
  4. Study completion1 Jan 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
240 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03583710
Sponsor's protocol ID
2017-0948
Other IDs
NCI-2018-01101, 2017-0948
Status last verified
Jul 2026
First submitted
28 Jun 2018
Last updated
16 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cisplatin, Etoposide and Mitotane in people with ENSAT Stage I Adrenal Cortex Carcinoma and ENSAT Stage II Adrenal Cortex Carcinoma, run by M.D. Anderson Cancer Center at 33 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in France, Sweden, United States, Germany, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jeena Varghese (713-792-2841, jvarghese@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recurrence-free survival (RFS) (time frame: From the time of randomization up to 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03583710.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2026.

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