Cabazitaxel Activity in Patients With Advanced AdrenoCortical-Carcinoma Progressing After Previous Chemotherapy Lines

NCT03257891 | Unknown Phase 2 DMC

• 1 other identifier: NP2729
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Adrenocortical cancer (ACC) is a rare aggressive tumor. The treatment of metastatic ACC is challenging and the current available treatments are mitotane, chemotherapy or the combination of both. Prognosis in locally advanced inoperable and metastatic ACC patients still remains poor, the 5-year overall survival being \<15%. New treatment strategies are therefore needed. The taxanes are a class of drugs targeting the microtubules that have shown to be effective in the treatment of several malignancies but have not been fully developed in patients with ACC. Cabazitaxel is a new taxoid which promotes the tubulin assembly in vitro and stabilizes microtubules against cold-induced depolymerization as efficiently as docetaxel. Cabazitaxel was selected for development based on a better antiproliferative activity on resistant cell lines than docetaxel. The activity of the drug against several malignancies is currently tested in ongoing prospective studies, but to our knowledge neither preclinical nor clinical studies are currently testing cabaztaxel in ACC. This study is aimed to demonstrate that cabazitaxel is active in ACC, but the drug was never tested before in this clinical setting. A prospective, non-randomized, multicentre, open label, single arm, phase II study will be conducted in patients with advanced ACC. The phase II study will be conducted in 2 different Italian Institutions that are reference centers for ACC.

Conditions

Adrenocortical Carcinoma

Keywords

Adrenocortical Carcinoma; Cabazitaxel

Outcome Measures

Primary Outcomes (1)

• To assess the clinical benefit after 4 months of the cabazitaxel in patients with locally advanced or metastatic ACC who progressed after cytotoxic therapy.

  CT scan evaluated according to RECIST 1.1 criteria

  4 months

Secondary Outcomes (5)

• Assessment of Objective Response Rates (ORR)

  Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year

• Assessment of overall survival

  Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year

• Assessment of quality of life

  Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year

• Assessment of toxicity

  Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year

• Assessment of hormone response

  Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year

Study Arms (1)

Arm 1

EXPERIMENTAL

patients with advanced Adrenocortical- Carcinoma progressing after previous chemotherapy lines will be treated with Cabazitaxel

Drug: Cabazitaxel

Interventions

Cabazitaxel DRUG

Cabazitaxel will be administered every 21 days

Arm 1

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
• Radiologically monitorised disease
• Progressing disease after one to three cytotoxic chemotherapy regimes (including a platin-based protocol)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy ≥ 3 months
• Age ≥ 18 years
• Adequate bone marrow reserve (neutrophils ≥ 1500/mm³ and platelets \> 100.000/mm³)
• Effective contraception in pre-menopausal female and male patients
• Patient´s written informed consent
• Ability to comply with the protocol procedures
• Mitotane intake should be stopped one months before the study entry

You may not qualify if:

• History of 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.
• Serum creatinine \> 1.5 x ULN or hepatic insufficiency, Hemoglobin \<10.0 g/dL;
• Total bilirubin \>1x ULN, Creatinine \< 1.5 ULN;
• Decompensated heart failure (ejection fraction \<45%), myocardial infarction or revascularization procedure during the last 6 months, unstable angina pectoris, uncontrolled cardiac arrhythmia
• Pregnancy or breast feeding
• 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
• Patients with serum levels of mitotane (evaluated one week before the study start) in the therapeutic range (14-20 mcg/ml).History of severe hypersensitivity reaction (≥grade 3) to docetaxel
• History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs
• Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)
• Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments) (see Annex 1 and Annex 2)
• Concomitant vaccination with yellow fever vaccine

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead
• San Luigi Gonzaga Hospital: collaborator

Study Sites (1)

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, 25123, Italy

RECRUITING

Related Publications (15)

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• Lagana M, Grisanti S, Ambrosini R, Cosentini D, Abate A, Zamparini M, Ferrari VD, Gianoncelli A, Turla A, Canu L, Terzolo M, Tiberio GAM, Sigala S, Berruti A. Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma. ESMO Open. 2022 Apr;7(2):100422. doi: 10.1016/j.esmoop.2022.100422. Epub 2022 Mar 7.

  PMID: 35272132 DERIVED

MeSH Terms

Conditions

Adrenocortical Carcinoma

Interventions

cabazitaxel

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

Study Officials

• Alfredo Berruti, MD

  Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alfredo Berruti, MD

CONTACT

030399; alfredo.berruti@gmail.com

Salvatore Grisanti, MD, PhD

CONTACT

030399; grisanti.salvatore@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: A prospective, non-randomized, multicentre, open label, single arm, phase II study will be conducted in patients with advanced ACC treated with Cabazitaxel

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: August 22, 2017
• Study Start: January 25, 2018
• Primary Completion: January 24, 2021
• Study Completion: January 24, 2022
• Last Updated: April 11, 2018

Record last verified: 2018-04

Locations

IT (1)