Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02882178 |
Other study ID # |
IB2012-CABOBS |
Secondary ID |
|
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
November 2013 |
Est. completion date |
April 2015 |
Study information
Verified date |
January 2021 |
Source |
Institut Bergonié |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
Cabazitaxel is a second line chemotherapy drug recently approved for the treatment of
metastatic castration-resistant prostate cancer. To investigate whether the precautions for
the use of cabazitaxel (contraindications, hepatic function, premedication for
hypersensitivity, prophylactic treatments, dose and dose adjustment, as well as conditions of
administration) are respected in routine practice, an observational cohort study will be
implemented in 32 oncology centres of South-West region of France (CABOBS study). The primary
objective of this cohort is to evaluate the conformity of cabazitaxel prescriptions with the
Summary of Product haracteristics (SPC) in clinical practice (indications and monitoring
methods) and according to the conditions of use. Panel of experts were convened to assess the
conformity of prescription of cabazitaxel with a Delphi consensus method. The Delphi method
is most suited to areas where a limited number of evidences are available to enable a
recommendation or guidelines to be drawn. Moreover, all the evaluated items came from an
official document provided by the EMA, the SPC of cabazitaxel. Thus, it is expected from the
experts to select the most relevant items. In the frame of the CABOBS study, this method will
allow to select items of the SPC list according to their importance, and to define the
primary objective of conformity to cabazitaxel conditions of use.
Description:
For metastatic castration-resistant prostate cancer (mCRPC) patients, treatment usually
consists in a first line chemotherapy with docetaxel followed by a second line treatment with
either second generation hormonal therapies (abiraterone acetate or enzalutamide) or the new
taxane derivative cabazitaxel. Cabazitaxel (Jevtana) is a semi-synthetic taxane with a
mechanism of action different to that of docetaxel and paclitaxel. It is an antineoplastic
agent that stabilises the microtubules network via its binding to tubulins and the inhibition
of microtubules disassembly. Cabazitaxel has demonstrated a broad spectrum of antitumour
activity against advanced human tumours xenografted in mice. It is active in
docetaxel-sensitive tumours and in tumour models resistant to chemotherapy, including
docetaxel. The efficacy of cabazitaxel has been demonstrated in the pivotal clinical trial
TROPIC, a randomized, open-label, phase III study that compared cabazitaxel (n = 378) to
mitoxantrone (n = 377), both associated with prednisone or prednisolone in patients with
hormone-refractory metastatic prostate cancer previously treated with a docetaxel containing
regimen. The median overall survival (OS) was significantly increased in the
cabazitaxel-treated group compared to the mitoxantrone-treated group. Most common adverse
event that can lead to a treatment discontinuation are haematological (neutropenia 82%),
gastrointestinal (diarrhoea 6%) and general disorders (asthenia 5%). A recent study analysed
the data of the TROPIC study on efficacy and toxicity observed in the subgroup of patients
included in French centres. These results are comparable to those reported for the overall
population and the safety profile remains favourable without any toxic death related to
cabazitaxel.
Following TROPIC trial, cabazitaxel (in combination with prednisone or prednisolone) was
approved by the U.S. Food and Drug Administration (FDA) on June 2010 and by the European
Medicines Agency (EMA) on March 2011 for the treatment of hormone-refractory prostate cancer.
In France cabazitaxel was approved in 2012 but made available only in 2014.
To investigate whether the precautions for the use of cabazitaxel (contraindications, hepatic
function, premedication for hypersensitivity, prophylactic treatments, dose and dose
adjustment, as well as conditions of administration) are respected in routine practice, an
observational cohort study will be implemented in 32 oncology centres of South-West region of
France (CABOBS study). The primary objective of this cohort is to evaluate the conformity of
cabazitaxel prescriptions with the Summary of Product Characteristics (SPC) in clinical
practice (indications and monitoring methods) and according to the conditions of use.
Based on the SPC, Specifications for prescription include 26 items divided into "baseline"
(14) criteria and "cycle 2" (12) criteria, which include requirements for the second and all
following cycles. Because of such high number of specific items, strict adherence to
prescription indications might be unsatisfactory or not appropriate from the clinical point
of view, each criterion has a different relevance on the appropriateness of prescription;
therefore, it is necessary to select the criteria based on their relevance and according to
the opinion of the clinical experts.
For this purpose, two independent panels of experts in the field of uro-oncology, one French
panel and a European panel from EORTC, were solicited in order to define the importance of
each criterion of the SPC and to allow a qualitative assessment of conformity using a formal
consensus method.
Consensus methods provide means of synthesising information and compare contradictory
opinions or evidences on a specific issue. Their purpose is to assess the extent of agreement
and to resolve disagreement among a group of selected individuals by identifying and
selecting, through iterative ratings with feedback, specific points on which there is
disagreement or uncertainty.
The Delphi method, a consensus method which originated in 1948, is an attempt to obtain
expert opinion in a systematic manner. The survey is conducted over "rounds" in which
questionnaires are administered to the experts individually and anonymously. After each
round, the results are listed and reported to the group. A Delphi is considered complete when
there is a convergence of opinion. In a modified Delphi usually a predefined number of rounds
and a final round, in which experts meet to resolve and summarise the results of the
consensus, are held.
The Sponsor relied on the Delphi method as it is most suited to areas where a limited number
of evidences are available to enable a recommendation or guidelines to be drawn. Moreover,
all the evaluated items came from an official document provided by the EMA, the SPC of
cabazitaxel. Thus, it is expected from the experts to select the most relevant items. In the
frame of the CABOBS study, this method will allow to select each of the 26 items of the SPC
list according to their importance, and to define the primary objective of conformity to
cabazitaxel conditions of use.