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

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ClinicalTrials.gov Identifier: NCT03257891
Recruitment Status : Recruiting
First Posted : August 22, 2017
Last Update Posted : April 11, 2018
Sponsor:
Collaborator:
San Luigi Gonzaga Hospital
Information provided by (Responsible Party):
Alfredo Berruti, Azienda Ospedaliera Spedali Civili di Brescia

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.

Condition or disease Intervention/treatment Phase
Adrenocortical Carcinoma Drug: Cabazitaxel Phase 2

Detailed Description:

CABAZITAXEL ADMINISTRATION Cabazitaxel will be administered at dose of 25 mg/m2 every 3 weeks, administered by IV route in 1 hour, for a maximum of 6 total cycles. The drug will be provided by Sanofi -Aventis S.p.A. Concomitant mitotane therapy will not be permitted however mitotane will be maintained in patients with hormone secreting tumors. Cycle length for cabazitaxel is 3 weeks. New cycles of therapy may not begin until Absolute Neutrophil Count (ANC) ≥1500/mm3, platelet count ≥75 000/mm3, and non-hematological toxicities (except alopecia) have recovered to baseline.

A maximum of 2 weeks delay is allowed between 2 treatment cycles.

PHARMACOKINETIC STUDY Another study aims will be to assess the toxicity of cabazitaxel therapy in ACC patients. As mitotane notoriously interfere with the metabolism of several drugs (11), an ancillary study will be conducted to assess the pharmacokinetic profile of cabazitaxel in the patient population with hormone secreting tumors that will maintain mitotane administration vs patients with non secreting ACC in which mitotane will be stopped. Blood samples will be collected in lithium heparinized tubes at fixed time points before and after drug infusion: Cycles 1 on Day 1 just before infusion, 30 min after start of infusion, 5 min before the end of 1-hour infusion (Tmax), 24 h, 48h and 96 h post-infusion. Cabazitaxel serum concentrations will be measured in plasma using a validated liquid chromatography-tandem mass spectrometry method: the Agilent 1260 Infinity LC equipped with an Agilent 6460 Triple Quadrupole Mass Spectrometer (QQQ) in electrospray mode systems.

STATISTICAL ANALYSIS All data collected at baseline, including recorded and derived variables will be described on all patients by means of summary descriptive statistics: mean, standard deviation, median, min, max, 25th and 75th percentiles for continuous variables; absolute and relative frequency for categorical variables. The relative frequencies will be calculated on the total patients with and without missing data. Whenever possible the data will be described by visit.

Chi square ore Fisher test, when applicable will be employed to compare categorical variables. Student T-test and analysis of variance for parametric or Wilcoxon's matched pairs signed-rank test and Friedman analysis of variance for non parametric data will be used to compare paired data. Simple correlation analysis will be performed by Spearman rho (coefficient of Spearman's rank correlation) for nonparametric distribution. Two-tailed tests will be used for all comparisons and p <0.05. All survival functions will computed using the Kaplan-Meier method. Survival curves will be compared with the log rank test.

CONCOMITANT MEDICATION Concurrent treatment with strong inhibitors and strong inducers of cytochrome P450 3A4 is not permitted. For patients who were receiving treatment with such agents, a 2-week washout period is required prior to randomization. Concurrent participation in another clinical trial or treatment with any other anti-cancer therapy is also not permitted. The Investigator may prescribe any other concomitant medications as deemed necessary.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Intervention Model Description: A prospective, non-randomized, multicentre, open label, single arm, phase II study will be conducted in patients with advanced ACC treated with Cabazitaxel
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Prospective, Non-randomized, Phase II Trial Designed to Evaluate the Activity of Cabazitaxel in Patients With Advanced Adreno-Cortical- Carcinoma Progressing After Previous Chemotherapy Lines
Actual Study Start Date : January 25, 2018
Estimated Primary Completion Date : January 24, 2021
Estimated Study Completion Date : January 24, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Cabazitaxel

Arm Intervention/treatment
Experimental: Arm 1
patients with advanced Adrenocortical- Carcinoma progressing after previous chemotherapy lines will be treated with Cabazitaxel
Drug: Cabazitaxel
Cabazitaxel will be administered every 21 days




Primary Outcome Measures :
  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. [ Time Frame: 4 months ]
    CT scan evaluated according to RECIST 1.1 criteria


Secondary Outcome Measures :
  1. Assessment of Objective Response Rates (ORR) [ Time Frame: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year ]
    ORR evaluated by RECIST criteria

  2. Assessment of overall survival [ Time Frame: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year ]
    defined as the time from the date of the study start to date of death due to any cause

  3. Assessment of quality of life [ Time Frame: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year ]
    EORTC quality of life questionnaire (QLQ)-C30 will be administered to patients

  4. Assessment of toxicity [ Time Frame: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year ]
    evaluated by NCI CTCAE V4.03 criteria

  5. Assessment of hormone response [ Time Frame: Every cycle (21 days) for a maximum of 6 cycles and for 6 months follow up. Total 1 year ]
    Evaluation of adrenocorticotropic hormone (ACTH), Testosterone, Progesterone, Cortisol, (Deidroepiandrosterone) DHEA-S, 17-hydroxide- progesterone, Androstenedione in serum. Evaluation of 24 hours urinary cortisol.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03257891


Contacts
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Contact: Alfredo Berruti, MD 030399 ext 5410 alfredo.berruti@gmail.com
Contact: Salvatore Grisanti, MD, PhD 030399 ext 5260 grisanti.salvatore@gmail.com

Locations
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Italy
Azienda Ospedaliera Spedali Civili di Brescia Recruiting
Brescia, Italy, 25123
Sponsors and Collaborators
Azienda Ospedaliera Spedali Civili di Brescia
San Luigi Gonzaga Hospital
Investigators
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Principal Investigator: Alfredo Berruti, MD Azienda Ospedaliera Spedali Civili di Brescia

Publications of Results:

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Responsible Party: Alfredo Berruti, MD, Azienda Ospedaliera Spedali Civili di Brescia
ClinicalTrials.gov Identifier: NCT03257891     History of Changes
Other Study ID Numbers: NP2729
First Posted: August 22, 2017    Key Record Dates
Last Update Posted: April 11, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alfredo Berruti, Azienda Ospedaliera Spedali Civili di Brescia:
Adrenocortical Carcinoma
Cabazitaxel
Additional relevant MeSH terms:
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Carcinoma
Adrenocortical Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Adrenal Cortex Neoplasms
Adrenal Gland Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Adrenal Cortex Diseases
Adrenal Gland Diseases
Endocrine System Diseases