Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03462888 |
| Other study ID # |
RMS-AJA-1701 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 2, 2018 |
| Est. completion date |
December 2024 |
Study information
| Verified date |
February 2024 |
| Source |
Centre Oscar Lambret |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Rhabdomyosarcoma (RMS) stands for the most frequent soft tissue sarcoma in children and,
adolescents and young adults (AYA, 15-25-year-old population), accounting for approximately
half of the whole soft tissue sarcomas in these populations.. Conversely, RMS represents a
very small proportion of the soft tissue sarcomas in adults (3%), that is less than 1% of all
solid cancers of adults.
To date, previous studies undertaken among the paediatric population have pointed out several
prognostic factors such as tumor localisation, tumor invasiveness at diagnosis, tumor size,
histological subset, and treatment plans. Age at diagnosis remains an independent prognostic
factor.
RMS management is consensual in Europe for paediatric population, essentially based on the
protocol RMS 2005 within the framework of the European Paediatric Soft tissue sarcoma Study
Group (EpSSG). Care in AYAs remain heterogeneous and are either achieved in paediatric
department, according to EpSSG guidelines, or in oncology department, known as "adult unit",
depending on ESMO (European Society for Medical Oncology), which are non-specific
recommendations for the management of rhabdomyosarcoma.
No consensus has been published yet for RMS in AYA despite the growing interest in cancers in
AYA population - topic.supported by the French National Cancer Institute (INCa) - and the
increasing network between paediatricians and adult-oncologists. Thus management of RMS in
AYA remains patchy/unequal depending on the type of care unit.
Herein, with the support of the Oscar Lambret Center, we aim at assessing and identifying
clinico-biological prognostic factors of rhabdomyosarcoma in AYA. Eventually, we hope to
offer a standardized treatment to this population. Data collected from medical file will be
anonymised in a confidential database of which the recipient is the sponsor of the study.
The ancillary study will aim at characterizing the molecular profile of the
difficult-to-classify RMS subtypes (fusiform or pleomorphic subsets) in molecular biology for
ambiguous cases.
From a scientific point of view, this study aims at understanding the parameters that may
influence the prognosis of RMS in AYAs by evaluating various clinical and biological factors.
Biologically, molecular profiling of RMS in AYA may improve the characterization of this
tumour in this age group.
At the clinical level, the completeness of the data collected will lead to a better
description of RMS in AYAs. We hope to harmonize their therapeutic management by providing
therapeutic adjustments according to population subsets.
Finally, these results could also help to adapt the therapeutic management of AYAs within the
framework of the European protocol that is currently under construction, and will involve
both children and adults.
Description:
Rhabdomyosarcoma (RMS) is a rare tumor, with an incidence rate estimated at 4.5-6.9/1,000,000
in paediatric and, adolescent and young adult (AYA, 15 -25 years old) populations. RMS stands
for the most frequent soft tissue sarcoma in children and adolescents, accounting for
approximately half of the whole soft tissue sarcomas in these populations. Conversely, RMS
represents a very small proportion of the soft tissue sarcomas in adults (3%), that is less
than 1% of the solid cancers of the adult. To date, previous studies undertaken among the
paediatric population have pointed out several prognostic factors such as tumor localisation,
tumor invasiveness at diagnosis, tumor size, histological subset, and treatment plans. Age at
diagnosis remains an independent prognostic factor. MYOD1 gene expression profile, more
common in AYA, also seems to impair the prognosis.
RMS management is consensual in Europe for paediatric population, essentially based on the
protocol RMS 2005 within the framework of the European Paediatric Soft tissue sarcoma Study
Group (EpSSG). Care in AYAs remain heterogeneous and are either achieved in paediatric
department, according to EpSSG guidelines, or in oncology department, known as "adult unit",
depending on ESMO (European Society for Medical Oncology), which are non-specific
recommendations for the management of rhabdomyosarcoma.
No consensus has been published yet for RMS in AYA despite the growing interest in cancers in
AYA population - topic.supported by the French National Cancer Institute (INCa) - and the
increasing network between paediatricians and adult-oncologists. Thus management of RMS in
AYA remains patchy/unequal depending on the type of care unit.
Principal study
- To evaluate the prognostic value in terms of Progression Free Survival (PFS), in AYA
patients with RMS, of clinical factors known as prognostic in children, and of
biological factors (MYOD1 mutation in non-alveolar tumor; FOXO1).
- To describe clinical, histological and biological characteristics of RMS in AYA.
- To describe the therapeutic strategy according to the type of department (pediatric, AYA
or adults):
- To evaluate the impact on PFS of treatment strategy
- To estimate the Overall Survival (OS) in AYA with RMS
- To estimate the OS curve after relapse for patients who achieved complete remission
during first line of treatment
Exploratory study Molecular profiling of RMS with the following subtypes: with fusiform cells
(Embryonal RMS with fusiform cells vs adult RMS with fusiform cells or sclerosing) or
pleomorphic (Embryonal RMS with anaplasia vs adult pleomorphic RMS) by RNAseq, and by CGH for
ambiguous cases.
Methodology Clinical data from the different databases will be merged using a standardized
format.
A pathology review of the slides is planned as well as a molecular characterization in
borderline cases and unusual subtypes. MYOD1 mutations and molecular profile will be
investigated for embryonal RMS.
Patient and treatment characteristics will be described with median, range, mean and standard
deviation for continuous variables and in terms of frequency and percent of each modality for
categorical variables.
PFS will be estimated using Kaplan-Meier method from diagnosis until relapse, progression or
death from any cause. Patients alive without progression will be censored at the date of last
news.
OS will be estimated using Kaplan-Meier method from diagnosis until death from any cause.
OS after relapse will be estimated using Kaplan-Meier method from the date of first relapse
until the death whatever the cause. Patients alive will be censored at the date of last news.
Prognostic factors of PFS will be analyzed using Cox models after check of the proportional
hazard assumption. The following factors will be evaluated:
- age: continuous or 15-18 vs 18-25
- tumor size: ≤ 5cm vs > 5cm
- primary tumor site according to the EPSSG classification: favorable (orbit, head and non
parameningeal neck, paratesticular, vagina, uterus) vs unfavorable (head and
parameningeal, vesico -prostatic, limb, other)
- IRS stage for primary tumor
- nodal and metastatic involvement at diagnostic
- histology (alveolar vs embryonic vs pleomorphic vs other)
- PAX3-FOXO1 and PAX7-FOXO1 fusion gene status, MYOD1 mutation The impact of treatment
intervention on PFS will be evaluated using a Cox model stratified or adjusted over
prognostic factors identified at the previous step.
