Recruiting
Phase 3

Mitotane with Cisplatin & Etoposide

Sponsor:

M.D. Anderson Cancer Center

Code:

NCT03583710

Conditions

ENSAT Stage I Adrenal Cortex Carcinoma

ENSAT Stage II Adrenal Cortex Carcinoma

ENSAT Stage III Adrenal Cortex Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Cisplatin

Etoposide

Mitotane

Quality-of-Life Assessment

Study Details

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.

Conditions

ENSAT Stage I Adrenal Cortex Carcinoma

ENSAT Stage II Adrenal Cortex Carcinoma

ENSAT Stage III Adrenal Cortex Carcinoma

Study ID

NCT03583710

Start date

Aug 20, 2018

Status verified date

Jul, 2026

Completion date

Jan 1, 2029

Anticipated

Primary completion date

Jan 1, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Study Design

Enrollment

240 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A (mitotane)

Patients 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.

experimental: Arm B (mitotane, etoposide, cisplatin)

Patients 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

Cisplatin

Given IV

Etoposide

Given IV

Mitotane

Given PO

Quality-of-Life Assessment

Ancillary studies

Primary outcome measure

  • Recurrence-free survival (RFS) [ Time Frame: From the time of randomization up to 2 years ]
  • Local recurrence of adrenocortical carcinoma (ACC) [ Time Frame: Up to 6 months ]
  • Distant recurrence of ACC [ Time Frame: Up to 6 months ]

Central Contacts and Locations

Central contacts

Jeena Varghese

713-792-2841jvarghese@mdanderson.org

Locations

University of Michigan Comprehensive Cancer Center

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Francis P. Worden

fworden@umich.edu

Principal Investigator:

Francis P. Worden

M D Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Jeena Varghese

713-792-2841jvarghese@mdanderson.org

Principal Investigator:

Jeena Varghese

More Information

Sponsor

M.D. Anderson Cancer Center

Last update posted

Jul 16, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by M.D. Anderson Cancer Center on 2026-07-16.