Activity of Abiraterone Acetate in the Management of Cushing's Syndrome in Patients With Adrenocortical Carcinoma

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT03145285
• Date of registration: 26/04/2017
• Prospective Registration: No
• Primary sponsor: Azienda Ospedaliera Spedali Civili di Brescia
• Public title: Activity of Abiraterone Acetate in the Management of Cushing's Syndrome in Patients With Adrenocortical Carcinoma ABACUS
• Scientific title: Activity of Abiraterone Acetate in the Management of Cushing's Syndrome in Patients With Adrenocortical Carcinoma
• Date of first enrolment: April 18, 2017
• Target sample size: 10
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03145285
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Italy

Contacts

• Name: Salvatore Grisanti, MD, PhD
• Affiliation: ASST Spedali Civili di Brescia

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cushing Syndrome

Adrenocortical Carcinoma

Intervention(s)

Drug: Abiraterone Acetate

Primary Outcome(s)

To assess the activity of AA in attaining normalization of 24-h urinary free cortisol (UFC) excretion relative to baseline within 1 month from treatment start [Time Frame: 1 month]

Secondary Outcome(s)

safety and tolerability of oral assumption of AA [Time Frame: Weekly, from date of treatment start, for the first month; once a month for the first 3 months; thereafter every 2 months up to 48 months]

treatment response (according to RECIST criteria) [Time Frame: every 3 months or earlier upon clinician's decision, up to 48 months]

improvement of quality of life [Time Frame: every visit up to 48 months]

improvement of the clinical signs associated to hypercortisolism [Time Frame: every visit up to 48 months]

time to syndrome relapse [Time Frame: every visit up to 48 months]

effect of AA on levels of serum cortisol, UFC, salivary cortisol, ACTH, aldosterone, PRA, DHEA-S, total testosterone, and steroid precursors [Time Frame: Monthly, from date of treatment start, for the first 3 months; thereafter every 2 months up to 48 months]

time to reduction of UFC (compared to screening values) [Time Frame: Weekly, from date of treatment start, for the first month; thereafter every 2 months up to 48 months.]

progression-free survival [Time Frame: every visit up to 48 months]

overall survival [Time Frame: every visit up to 48 months]

to assess the activity of AA in attaining 50% reduction of 24-h UFC excretion within 1 month of treatment [Time Frame: 1 month]

Secondary ID(s)

2016-000945-29

ASSTBS-ONCO-ABACUS-16

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Niguarda Hospital

San Camillo Hospital, Rome

San Luigi Gonzaga Hospital