Neoplasms

All Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Adrenocortical Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Adrenal Cortex Neoplasms

Adrenal Gland Neoplasms

Endocrine Gland Neoplasms

Adrenal Cortex Diseases

Adrenal Gland Diseases

Endocrine System Diseases

Antineoplastic Agents

All Drugs and Chemicals

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Central Nervous System Stimulants

Anti-Infective Agents

Etoposide

Doxorubicin

Liposomal doxorubicin

Cisplatin

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Megestrol Acetate

Etoposide phosphate

Progesterone

Mitotane

Anti-Bacterial Agents

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Enzyme Inhibitors

Contraceptive Agents

Contraceptives, Oral

Contraceptives, Oral, Hormonal

Contraceptive Agents, Female

Contraceptive Agents, Hormonal

Antineoplastic Agents, Hormonal

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. Concomitant mitotane therapy will be administered continuously. Megestrole 160 mg 2 tablets will be administered once daily (in the morning) and will be stopped 21 days after the last administration of the EDP.

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. Concomitant mitotane therapy will be administered continuously. Placebo 2 tablets will be administered once daily (in the morning) and will be stopped 21 days after the last administration of the EDP.

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.).

Etoposide, 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. Placebo 160 mg tablets will be developed by the CDMO to have the same appearance and taste as the tablet containing the active drug.

Etoposide, doxorubicin, cisplatin and Mitotane plus Placebo

Aldo Roccaro

Alfredo Berruti

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.

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)

Comparison of proportion of patients attaining an Objective Response (Objective Response Rate, ORR), evaluated by RECIST criteria between the 2 treatment arms.

Changes in serum cortisol from baseline in the two treatment arms;

Changes in serum UFC from baseline in the two treatment arms;

Changes in serum salivary cortisol from baseline in the two treatment arms;

Changes in ACTH from baseline in the two treatment arms;

Changes in serum 11-deoxycortisol from baseline in the two treatment arms;

Changes in serum aldosterone from baseline in the two treatment arms;

Changes in serum PRA from baseline in the two treatment arms;

Changes in serum androstenedione from baseline in the two treatment arms;

Changes in serum DHEA-S from baseline in the two treatment arms;

Changes in serum progesterone from baseline in the two treatment arms;

Changes in serum total testosterone from baseline in the two treatment arms;

Spots Global Cancer Trial Database for etoposide, doxorubicin, cisplatin and mitotane plus placebo