Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03676218 |
| Other study ID # |
IB2016-DATECAN-elderly |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2017 |
| Est. completion date |
December 2023 |
Study information
| Verified date |
July 2023 |
| Source |
Institut Bergonié |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Context and hypothesis: In cancer randomized controlled trials (RCT), the validated and most
objective criterion to assess treatment efficacy is overall survival (OS). In the elderly
population, OS presents limitations as it can be affected by factors other than treatment
such as comorbidity or severe toxicity. Although mortality reduction is important for
patients of all ages, alternative outcomes such as the ability to live independently or with
a better quality of life, may be more important for older patients.
Reviews of RCT have highlighted (i) the heterogeneity of such alternative efficacy outcomes
and (ii) an absence of standardized definitions for these endpoints. As a result, this may
limit the quality of RCT as well as the comparison of results across trials. Our objective is
to provide guidelines for standardized definitions of such alternative endpoints to assess
treatment efficacy in cancer RCT in elderly populations.
The development of guidelines will follow a formal consensus method (questionnaires +
in-person meetings). A large panel of international experts will participate.
Guidelines are awaited due to the heterogeneity of endpoints and absence of standardized
definitions. Standardizing definitions will improve the quality and design of future trials
and enhance comparison between trials.
Description:
In cancer randomized controlled trials (RCT), the validated and most objectively defined
evaluation criterion is overall survival (OS - delay between randomization and death).
Therapeutic progress, the current context of strategic trials, and the multiplication of
lines of treatment have resulted in the necessity to identify evaluation criteria other than
OS, which can be observed more frequently and sooner. Endpoints such as progression-free
survival (PFS) or disease-free survival (DFS) are commonly used instead of OS in RCT. The
priority for patients, however, is to live longer or better, and ideally both, which raises
the question as to the suitability of these tumor-specific endpoints to assess the
benefit/risk balance associated to a new therapy in elderly patients with cancer. Older
patients may die from causes other than cancer, and relapse does not necessarily shorten
survival. Instead, cancer therapy can sometimes cause severe acute or chronic toxicities and
affect functional status or health-related quality of life (HRQoL), and as such these
patient-centered outcomes (e.g. autonomy, quality of life) should be given more attention. On
the basis of these considerations, OS may not be the most appropriate outcome to measure
treatment benefit in the elderly cancer population.
Geriatric oncology experts and task forces including the International Society of Geriatric
Oncology, the European Organization for Research and Treatment Cancer (EORTC) and the DIALOG
research group (Dialogue Intergroupe pour la personnALisation de la prise en charge en
OncoGériatrie), have acknowledged the heterogeneity of primary endpoints used in RCT
conducted in elderly cancer patients. This heterogeneity, in terms of dimension
(tumor-centered outcomes, patient-centered outcomes including autonomy, nutrition, etc.) and
definitions limits the comparison of results across trials. In addition, this can make the
design of trials particularly complex since estimation of sample size is usually based on
results from past trials. Acknowledging the specificities of the elderly population, the
DATECAN-Elderly project is aimed at providing guidelines for the definition of efficacy
endpoints that will permit to assess new treatments/interventions in this population.
The DATECAN-Elderly project is a continuation of the development of guidelines within the
DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer
trials). This international initiative was launched in 2009 to elaborate standardized
definitions for survival endpoints in RCT, based on a rigorous and validated consensus
methodology. This work has resulted in the publication of guidelines to define time-to-event
endpoints to be used in randomized trials for specific cancer sites: sarcomas, pancreas,
breast, and other. These guidelines however were not developed for the elderly cancer
patients. Events specifically accounted for included exclusively tumor-oriented events (e.g.
local, regional, metastatic progressions, or deaths due to various causes).
Based on our past experience and expertise within the DATECAN initiative, we will rely on the
same methodology to develop guidelines for the definitions of endpoints to assess treatment
efficacy in elderly cancer RCT. The development of the definitions of the endpoints will be
based on a rigorous and validated consensus methodology (formal modified Delphi consensus
process). We will focus on (i) the dimensions to be accounted for when assessing treatment
efficacy (OS, HRQoL, autonomy, etc), (ii) the quantification of dimensions (selection of the
questionnaires), and (iii) the incorporation of these dimensions into trial design.
DATECAN-Elderly guidelines will be developed in cooperation with many experts (30 to 50) in
the field of geriatric oncology and clinical trials from different scientific backgrounds
(medical oncologists, geriatricians, biostatisticians, etc.) and groups/societies (DIALOG,
SIOG, EORTC, etc.), favouring the acceptability of the resulting recommendations.
Recommendations developed through international collaborations and through a formal and
validated consensus process can increase chances of becoming widely adopted through a
democratic process to reach consensus, and, as such, help in the standardization process of
the definitions.
Results of the DATECAN-Elderly project are expected to address the heterogeneity regarding
efficacy endpoints used as primary endpoints in elderly cancer trials. Providing definitions
for endpoints should lead to the evaluation of treatment more consistent with patient's
experiences and expectations about treatment outcome. Overall, the project should help
provide trials' results which are more relevant for the elderly patients, improves the
recruitment of elderly patient in RCT, and finally enhance trials' comparison and design.
