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.
As no effective second-line therapies are available for patients with disease progression to EDPM, including modern molecular target therapies and immunotherapy, it is reasonable to expect that no newer drugs or combination regimens will be able to replace EDPM in the next 5 years. Since EDP-M is destined to remain the standard first line therapy, research strategies aimed to improve the efficacy of this regimen are of relevance. In this study, investigators will address the hypotheses that progesterone has a synergistic and/or additive effect to EDP-M in inducing cytotoxicity in ACC cells in vitro and the antineoplastic activity of EDP-M in locally advanced/metastatic ACC patients could be improved by the addition of megestrol acetate.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
80
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.).
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.
Alfredo Berruti
Brescia, Italy
RECRUITINGEvaluation of the activity of the combination regimen (EDP-M plus progesterone (EDP-MP) versus EDP-M plus placebo) in advanced/ metastatic patients with ACC.
Comparison of proportion of patients attaining an Objective Response (Objective Response Rate, ORR), evaluated by RECIST criteria between the 2 treatment arms.
Time frame: 18 months
Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;
Changes in serum cortisol from baseline in the two treatment arms;
Time frame: 18 months
Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;
Changes in serum UFC from baseline in the two treatment arms;
Time frame: 18 months
Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;
Changes in serum salivary cortisol from baseline in the two treatment arms;
Time frame: 18 months
Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;
Changes in ACTH from baseline in the two treatment arms;
Time frame: 18 months
Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;
Changes in serum 11-deoxycortisol from baseline in the two treatment arms;
Time frame: 18 months
Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;
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Changes in serum aldosterone from baseline in the two treatment arms;
Time frame: 18 months
Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;
Changes in serum PRA from baseline in the two treatment arms;
Time frame: 18 months
Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;
Changes in serum androstenedione from baseline in the two treatment arms;
Time frame: 18 months
Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;
Changes in serum DHEA-S from baseline in the two treatment arms;
Time frame: 18 months
Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;
Changes in serum progesterone from baseline in the two treatment arms;
Time frame: 18 months
Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;
Changes in serum total testosterone from baseline in the two treatment arms;
Time frame: 18 months