Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03252717 |
| Other study ID # |
ICM-URC-2014/22 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 2014 |
| Est. completion date |
August 2022 |
Study information
| Verified date |
October 2020 |
| Source |
Institut du Cancer de Montpellier - Val d'Aurelle |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
To confirm the protein expression level in radiation-induced late effects patients and to
determine the performance value, in particular the positive predictive value, of a blood test
based on the dosage of a panel of five proteins, it is necessary to validate these
preliminary results by a prospective study on a large cohort of patients.
Description:
Molecular mechanisms involved in radiation-induced responses are complex, and proteomic
approaches can be used to better understand the overall reaction process of ionizing
radiation and to identify potential radio-sensitive predictive markers. Until now, few
publications have addressed the determination of radiosensitive patients.
Based on our previous results and in order to improve the positive predictive value of the
radiation induced late effect assay, we developed a quantitative proteomic approach to
identify predictive radiobiological markers in patients with severe toxicity. First, four
patients were selected with a low RILA value from the prospective studies mentioned above.
Two patients had no toxicity at least four years after the end of treatment whereas two
others patients developed a severe toxicity greater than grade 2. T-lymphocytes have been
isolated from whole blood and half of them have been irradiated in vitro. It will then
performed a quantitative proteomics workflow using an 8-plex iTRAQ labeling and after several
fractionations to optimize resolution of analysis (off gel fractionation followed by
nanoliquid chromatography), proteins were identified by tandem mass spectrometry (4800 plus
MALDI TOF/TOF). More than 1300 total proteins were identified with high confidence (95%, one
unique peptide). At 0 Gy, 135 proteins were differentially expressed between patients with or
without severe radio-induced toxicity. In irradiated T-lymphocytes (8 Gy), 107 proteins were
differentially expressed between patients with or without severe radio-induced toxicity.
Among them, five proteins (AK2, adenylate kinase 2; IDH2, isocitrate dehydrogenase 2 (NADP+);
ANX1, annexin 1; APEX1, DNA-(apurinic or apyrimidinic site) lyase, and HSC70, Heat shock
cognate 71 kDa) with the highest protein expression ratio (>1.5) and that showed no
difference expression ratio in 0 Gy controls, were selected for consecutive validation. These
proteins are involved in several mechanisms including metabolism and energy production,
apoptosis, calcium binding protein, and DNA damages repair. These five proteins are currently
the subject of patent application.
Then,10 other patients will be recruited (5 patients with grade ≥ 2 breast fibrosis and 5
patients without toxicity) who presented a low RILA value to validate proteins expression by
western-blotting. Results showed that all proteins were overexpressed in irradiated
T-lymphocytes patients with severe toxicity comparatively to patients without toxicity.
However, to confirm the protein expression level in radiation-induced late effects patients
and to determine the performance value, in particular the positive predictive value, of a
blood test based on the dosage of a panel of five proteins, it is necessary to validate these
preliminary results by a prospective study on a large cohort of patients
