2022-500013-32-01招募中3 期
Adjuvant mitotane vs. mitotane with cisplatin/etoposide after primary surgical resection of localised adrenocortical carcinoma with high risk of recurrence (ADIUVO-2 Trial): A pragmatic, randomised, low-intervention phase III, clinical trial with an observational arm.
Uppsala University Hospital, Universitaetsklinikum Wuerzburg AöR, Assistance Publique Hopitaux De Paris23 个研究点 分布在 3 个国家目标入组 120 人开始时间: 2022年12月19日最近更新:
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 23
- 主要终点
- RFS will be defined as the time between the date of randomisation until documentation of radiological evidence of local recurrence, radiological evidence of distant recurrence or date of death from any cause, whichever occurs first. Patients will be censored at the date of their last evaluation in which they were known to be alive and recurrence-free, regardless of whether recurrence status was verified during that contact (e.g., phone contact).
研究概览
简要总结
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.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •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 12 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).
排除标准
- •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
研究组 & 干预措施
-
Auxiliary
Participants receiving -
干预措施: - (Drug)
结局指标
主要结局
RFS will be defined as the time between the date of randomisation until documentation of radiological evidence of local recurrence, radiological evidence of distant recurrence or date of death from any cause, whichever occurs first. Patients will be censored at the date of their last evaluation in which they were known to be alive and recurrence-free, regardless of whether recurrence status was verified during that contact (e.g., phone contact).
RFS will be defined as the time between the date of randomisation until documentation of radiological evidence of local recurrence, radiological evidence of distant recurrence or date of death from any cause, whichever occurs first. Patients will be censored at the date of their last evaluation in which they were known to be alive and recurrence-free, regardless of whether recurrence status was verified during that contact (e.g., phone contact).
次要结局
- Overall survival is defined as the time interval between the date of randomisation and the date of death from any cause.
- Assessment of the effect of serum mitotane levels, disease stage, Ki67 index and status of resection margins on clinical outcomes based on physical examination, complete blood count with differential, serum chemistry profile, endocrine assessment and serum mitotane measurement at baseline and until ACC recurrence. The effect will also be assessed using cross-sectional imaging (CT with contrast medium, MRI) of the chest/abdomen/pelvis or FDG PET-CT every 12 weeks until ACC recurrence.
- The effect of early vs. late start of adjuvant therapy on clinical outcomes will be assessed in a similar manner as above.
- Quality of life will be measured at baseline, 6 weeks and 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 (EORTC QLQ-C30).
- Serious adverse events, grade 3 and above, will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0) until one year after end of treatment.
研究者
Department of Endocrine Oncology
Scientific
Uppsala University Hospital
研究点 (23)
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