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

April 10, 2018 updated by: Alfredo Berruti, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Brescia, Italy, 25123
        • Recruiting
        • Azienda Ospedaliera Spedali Civili di Brescia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
4 months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Collaborators

San Luigi Gonzaga Hospital

Investigators

  • Principal Investigator: Alfredo Berruti, MD, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 25, 2018

Primary Completion (Anticipated)

January 24, 2021

Study Completion (Anticipated)

January 24, 2022

Study Registration Dates

First Submitted

August 17, 2017

First Submitted That Met QC Criteria

August 19, 2017

First Posted (Actual)

August 22, 2017

Study Record Updates

Last Update Posted (Actual)

April 11, 2018

Last Update Submitted That Met QC Criteria

April 10, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NP2729

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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