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Adjuvant therapy in high risk adrenocortical carcinoma (ADIUVO-2)
EU CTIS ID: 2022-500013-32-01
What this study is testing
The primary objective is 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 RFS in patients with high-risk ACC after initial surgical resection.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Histologically confirmed diagnosis of ACC (Weiss score of ≥ 3). Lin-Weiss-Bisceglia system will be used for oncocytic ACC.
- High risk of relapse defined as: Stage I–III ACC (according to the ENSAT classification) within 90 days of surgical resection of primary tumour 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 centre will determine the pathological stages and resection margins; AND, Ki67>10% (to be determined by an experienced pathologist in each participating centre and preferably via quantitative imaging analysis).
- Perioperative imaging (CT with contrast, MRI of the chest/abdomen/pelvis, or FDG-PET CT) without unequivocal evidence of metastatic disease within 6 weeks before randomisation (ideally within 4 weeks). 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.
- 18 years of age or older
- Eastern Cooperative Oncology Group performance status 0–2
- Women of childbearing potential and men should use appropriate contraceptive measures to avoid pregnancy during therapy.
You likely can't join if
- The time between primary surgery and randomisation is >90 days
- Contraindication to mitotane, etoposide or cisplatin, as reported in the respective SmPC
- Gross residual disease after surgery (R2 resection)
- High suspicion for metastatic disease on perioperative imaging
- Patients that have undergone repeated surgery for recurrence of disease
- History of recent or active prior malignancy, except for cured non-melanoma skin cancer, or cured in situ cervical carcinoma, or breast ductal carcinoma in situ, or other treated malignancies where there has been no evidence of disease for at least 2 years.
See the full eligibility criteria
Who can join
- Histologically confirmed diagnosis of ACC (Weiss score of ≥ 3). Lin-Weiss-Bisceglia system will be used for oncocytic ACC.
- High risk of relapse defined as: Stage I–III ACC (according to the ENSAT classification) within 90 days of surgical resection of primary tumour 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 centre will determine the pathological stages and resection margins; AND, Ki67>10% (to be determined by an experienced pathologist in each participating centre and preferably via quantitative imaging analysis).
- Perioperative imaging (CT with contrast, MRI of the chest/abdomen/pelvis, or FDG-PET CT) without unequivocal evidence of metastatic disease within 6 weeks before randomisation (ideally within 4 weeks). 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.
- 18 years of age or older
- Eastern Cooperative Oncology Group performance status 0–2
- Women of childbearing potential and men should use appropriate contraceptive measures to avoid pregnancy during therapy.
- Ability to comply with the protocol procedures
- Provide written informed consent
- [France] Affiliation with a mode of social security (profit or being entitled).
What rules you out
- The time between primary surgery and randomisation is >90 days
- Contraindication to mitotane, etoposide or cisplatin, as reported in the respective SmPC
- Gross residual disease after surgery (R2 resection)
- High suspicion for metastatic disease on perioperative imaging
- Patients that have undergone repeated surgery for recurrence of disease
- History of recent or active prior malignancy, except for cured non-melanoma skin cancer, or cured in situ cervical carcinoma, or breast ductal carcinoma in situ, or other treated malignancies where there has been no evidence of disease for at least 2 years.
- Protected adults (including individual under guardianship by court order) and persons deprived of their liberty by a judicial or administrative decision.
- Renal insufficiency (estimated glomerular filtration rate [GFR]<50 mL/min/1.73m2) or significant liver insufficiency (serum bilirubin>2 times the upper normal range and/or serum alanine aminotransferase [ALT] or aspartate aminotransferase [AST]>3 times the upper normal range). GFRs will be calculated according to the validated formula (MDRD).
- Impaired bone marrow reserve (neutrophils< 1000/mm3 and/or platelets < 100,000/mm3)
- Breast feeding
- Congestive heart failure defined as having moderate or severe systolic left ventricular dysfunction (ejection fraction<40%). The extent of cardiac testing will depend on the judgment of the local 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 randomised to mitotane who do not have prior cardiac history and have low suspicion for cardiac symptoms to reflect standards of clinical practice. Similarly, utilising cardiac imaging and EKG within the past 12 months is permitted if there is no suspicion for cardiac issues.
- 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.
- Preexisting grade 2 peripheral neuropathy
- Patients that underwent previous or current treatment with mitotane or other antineoplastic drugs for ACC
- Patients that underwent previous radiotherapy for ACC
The study team makes the final eligibility decision.
Where it's taking place
- United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.