RecruitingPhase 2NCT05913427

Evaluation of the Efficacy of Addition of Progesterone to Standard Chemotherapy in Adrenocortical Carcinoma (ACC)

Prospective, Phase II Study to Evaluate the Efficacy of Addition of Progesterone to Standard Chemotherapy According to Etoposide-Doxorubicin-Cisplatin Scheme Plus Mitotane (EDP-M) in Patients With Advanced Adrenocortical Carcinoma (ACC)

Sponsor

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Enrollment

80 participants

Start Date

Jun 8, 2022

Study Type

INTERVENTIONAL

Conditions

Adrenocortical Carcinoma

Summary

This is a prospective randomized, double blind, placebo controlled phase II study planned in patients with advanced ACC. The study will be conducted at ASST Spedali Civili Hospital and University of Brescia in Brescia.

Eligibility

Min Age: 18 Years

Inclusion Criteria8

Histologically confirmed diagnosis of ACC
Locally advanced or metastatic disease not amenable to radical surgery resection
ECOG performance status 0-2
Effective contraception
Life expectancy \> 3 months
Age \> 18 years
Adequate bone marrow reserve (neutrophils \>1,000/mm3 and/or platelets \>80,000/mm3) and organ function (including renal, liver and cardiac function)
Be able to comply with the protocol procedures and provide written informed consent.

Exclusion Criteria8

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
Renal insufficiency (estimated glomerular filtration rate \[GFR\]\<50 mL/min/1.73 m2) 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)
Pregnancy or breast feeding
Congestive heart failure (ejection fraction\<45%)
Preexisting grade 2 peripheral neuropathy
Previous or current treatment with mitotane or other antineoplastic drugs for ACC
Previous radiotherapy for ACC
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 that, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Interventions

DRUGEtoposide, doxorubicin, cisplatin and Mitotane plus Megestrol Acetate 160 MG

EDP will be administered at the following doses: doxorubicin 40 mg/m2 on day 1, etoposide 100 mg/m2 days 2-4, cisplatin 40 mg/m2 days 3-4, every 28 days. Megestrol acetate will be prepared and packaged by the authorized external contract development and manufacturing organization (CDMO) Doppel Farmaceutici s.r.l. (Cortemaggiore, PC), that, according to the GMP and applicable law (FU XII ed) will also prepare the related placebo, in accordance with GMP (annex 13) and applicable law (FU XII ed.).

DRUGEtoposide, doxorubicin, cisplatin and Mitotane plus Placebo

EDP will be administered at the following doses: doxorubicin 40 mg/m2 on day 1, etoposide 100 mg/m2 days 2-4, cisplatin 40 mg/m2 days 3-4, every 28 days. Placebo 160 mg tablets will be developed by the CDMO to have the same appearance and taste as the tablet containing the active drug.