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

NCT05913427 | Recruiting Phase 2 DMC

• 1 other identifier: ASSTBS-FARONCO- PESETA-20
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Adrenocortical Carcinoma

Outcome Measures

Primary Outcomes (1)

• Evaluation 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.

  18 months

Secondary Outcomes (11)

• Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;

  18 months

• Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;

  18 months

• Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;

  18 months

• Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;

  18 months

• Evaluation of the impact of the combination of the two treatments on hormone response in patients with secreting ACC;

  18 months

Study Arms (2)

EDP-M plus MEGESTROL ACETATE 160 mg

EXPERIMENTAL

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.

Drug: Etoposide, doxorubicin, cisplatin and Mitotane plus Megestrol Acetate 160 MG

EDP-M plus PLACEBO

PLACEBO COMPARATOR

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.

Drug: Etoposide, doxorubicin, cisplatin and Mitotane plus Placebo

Interventions

Etoposide, doxorubicin, cisplatin and Mitotane plus Megestrol Acetate 160 MG DRUG

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.).

Also known as: Megace

EDP-M plus MEGESTROL ACETATE 160 mg

Etoposide, doxorubicin, cisplatin and Mitotane plus Placebo DRUG

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.

Also known as: placebo

EDP-M plus PLACEBO

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead

Study Sites (1)

Alfredo Berruti

Brescia, 25123, Italy

RECRUITING

Related Publications (5)

• Fassnacht M, Assie G, Baudin E, Eisenhofer G, de la Fouchardiere C, Haak HR, de Krijger R, Porpiglia F, Terzolo M, Berruti A; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Nov;31(11):1476-1490. doi: 10.1016/j.annonc.2020.08.2099. Epub 2020 Aug 27. No abstract available.

  PMID: 32861807 RESULT

• Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, Welin S, Schade-Brittinger C, Lacroix A, Jarzab B, Sorbye H, Torpy DJ, Stepan V, Schteingart DE, Arlt W, Kroiss M, Leboulleux S, Sperone P, Sundin A, Hermsen I, Hahner S, Willenberg HS, Tabarin A, Quinkler M, de la Fouchardiere C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Muller HH, Skogseid B; FIRM-ACT Study Group. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012 Jun 7;366(23):2189-97. doi: 10.1056/NEJMoa1200966. Epub 2012 May 2.

  PMID: 22551107 RESULT

• Fiorentini C, Fragni M, Perego P, Vezzoli S, Bonini SA, Tortoreto M, Galli D, Claps M, Tiberio GA, Terzolo M, Missale C, Memo M, Procopio G, Zaffaroni N, Berruti A, Sigala S. Antisecretive and Antitumor Activity of Abiraterone Acetate in Human Adrenocortical Cancer: A Preclinical Study. J Clin Endocrinol Metab. 2016 Dec;101(12):4594-4602. doi: 10.1210/jc.2016-2414. Epub 2016 Sep 14.

  PMID: 27626976 RESULT

• Fragni M, Fiorentini C, Rossini E, Fisogni S, Vezzoli S, Bonini SA, Dalmiglio C, Grisanti S, Tiberio GAM, Claps M, Cosentini D, Salvi V, Bosisio D, Terzolo M, Missale C, Facchetti F, Memo M, Berruti A, Sigala S. In vitro antitumor activity of progesterone in human adrenocortical carcinoma. Endocrine. 2019 Mar;63(3):592-601. doi: 10.1007/s12020-018-1795-x. Epub 2018 Oct 26.

  PMID: 30367443 RESULT

• Rossini E, Tamburello M, Abate A, Beretta S, Fragni M, Cominelli M, Cosentini D, Hantel C, Bono F, Grisanti S, Poliani PL, Tiberio GAM, Memo M, Sigala S, Berruti A. Cytotoxic Effect of Progesterone, Tamoxifen and Their Combination in Experimental Cell Models of Human Adrenocortical Cancer. Front Endocrinol (Lausanne). 2021 Apr 26;12:669426. doi: 10.3389/fendo.2021.669426. eCollection 2021.

  PMID: 33981288 RESULT

MeSH Terms

Conditions

Adrenocortical Carcinoma

Interventions

Etoposide; Doxorubicin; Cisplatin; Mitotane; Megestrol Acetate

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Hydrocarbons, Chlorinated; Hydrocarbons, Halogenated; Megestrol; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Alfredo Berruti

  ASST Spedali Civili di Brescia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aldo Roccaro

CONTACT

+390303996851; coordinamento.ricerca@asst-spedalicivili.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: March 7, 2023
• First Posted: June 22, 2023
• Study Start: June 8, 2022
• Primary Completion (Estimated): June 8, 2027
• Study Completion (Estimated): June 8, 2027
• Last Updated: August 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)