Activity of Abiraterone Acetate in the Management of Cushing's Syndrome in Patients With Adrenocortical Carcinoma (ABACUS)
Cushing Syndrome, Adrenocortical Carcinoma
About this trial
This is an interventional treatment trial for Cushing Syndrome focused on measuring Abiraterone Acetate, Cushing Syndrome, Adrenocortical Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Histologically-confirmed diagnosis of ACC
- CT or MRI evidence of metastatic or locally advanced ACC (ENSAT stage III-IV) unsuitable for radical surgery
- Age ≥ 18 years
- Confirmed diagnosis of Cushing's syndrome validated by:
- two 24 h urinary collections for UFC at least 1.5 times the upper the normal levels, within 2 weeks prior to enrollment;
- serum ACTH levels lower than the normal range;
- ECOG performance status ≤ 2
- Effective contraception
- Patients must provide verbal and written informed consent to be enrolled in the study
Exclusion Criteria:
- Life expectancy less than 3 months
- Liver disease, such as cirrhosis, chronic or persistent active hepatitis or AST/ALT > 2 x ULN, bilirubin >2 x ULN
- Heart failure (NYHA class III or IV), unstable angina, severe arrhythmia or clinically significant impairment of heart function
- Major surgical procedure within one month prior entering the study
- Renal impairment (creatinine clearance < 40 ml/min).
- WBC <3 x 109 /L; Hb <13 g/dL for men and <12 g/dL for women; platelets <100 x 109 /L
- Any other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- Pregnant or breast-feeding women
- History of alcohol or drug abuse
- History of recent or active prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least three years)
- Acute or chronic uncontrolled infections
- Patient non-compliance
Sites / Locations
- U.O Oncologia Medica
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Cohort 1
Cohort 2
Patients locally advanced/metastatic ACC patients with uncontrolled Cushing's syndrome despite Mitotane +/- chemotherapy. Treatment with single agent Abiraterone Acetate (AA) until progression
Mitotane-naïve patients with newly diagnosis of ACC associated with Cushing's syndrome not amenable to surgical resection. Treatment with single agent Abiraterone Acetate (AA) for 4 weeks followed by AA + Mitotane +/- first-line chemotherapy. AA in association with Mitotane will be administered for 3 months. If the primary endpoint is obtained before 1 month, then Mitotane +/- chemotherapy can be started upon the clinician's decision.