The circulating tumoral biomarkers in the blood are the object of numerous researches for several decades. The potential clinical interests of these circulating biomarkers are diagnostic, prognostic, predictive of the efficiency of targeted therapies (according to the mutational profile of the cancer), and could allow the study of the mechanisms of resistance under process. In the multiplicity of these blood potential biomarkers joins a permanent evolution of the technological means used to detect them/to quantify, as well as to estimate their clinical utility.
The new major challenge in the research concerns the circulating biomarkers, which aim at replacing the molecular analyses on tumour tissue obtained by biopsy (for example the search for somatic mutations of cancer) by a simple blood test (liquid biopsy). The other current important challenge is to have an idea of the interest to analyse the kinetics of blood markers, in particular in answer to a clinical "event", either through the chemotherapy, a biopsy and / or surgery. There is almost no data in the literature on this aspect. It is very likely that the liberation in the blood of the blood tumoral markers is strongly dependent on medical interventions on the tumour. The study ALCINA 2 rests exactly on the principle of small cohorts, which correspond each to a clinical situation and/or a technique of different implemented detection, so as to generate data of feasibility and proof of concept. In case of success, statistical hypotheses will be necessary for the implementation of wider studies (being then the object of a specific approval by competent authorities).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
992
blood sampling time : cycle 1 day 15 and cycle 2 day 15 : one sample (6ml) by time
Blood samples will be collected at four key time points: * baseline (T1), * first scan assessment (T2), * second scan assessment (T3), * and progression (T4).
Blood samples will be collected before any treatment
Blood samples will be collected at four key time points: * At the inclusion (T1) * Before the beginning of the treatment (cycle 1 day 1) (T2) * After the first cycle of T-DXd (cycle 2 day 1) (T3) * At progression or at the end of the follow-up (after 3 years) (T4)
Blood samples will be collected at three key time points: * At the inclusion (T1) * For patients starting treatment at the time of inclusion (T2): * Chemotherapy: 3 months after inclusion, * Concurrent chemoradiotherapy with Temozolomide: 4-6 weeks after completion of radiotherapy, * For patients starting treatment at the time of inclusion: at the time of tumor progression if occurring within one year of inclusion, or 12 months after inclusion in the absence of progression (T3).
Blood samples will be collected at five key time points: * At the inclusion * At follow-up visit 2 to 6, every 3 months
Blood samples will be collected at four key time points: * At the inclusion before the beginning of the treatment (Cycle 1 Day 1) * After the first cycle of the first chemo-immunotherapy sequence (Cycle 2 Day 1) * After the first cycle of the second chemotherapy sequence (Cycle 2b Day 1) * After the end of the whole neo-adjuvant chemo-immunotherapy protocol, before surgery
Blood samples will be collected at five key time points: * At the inclusion (T1) * At first clinical evaluation (T2): 4th week after start of treatment * At first scan evaluation (T3a): 8th week after start of treatment * At the Nth scan evaluation (T3b, c, ...) * At progression (T4) Tumor sampling : * At the inclusion * At tumor progression
Blood samples will be collected at several points : * Inclusion: at the time of suspected leptomeningeal metastases, prior to any specific treatment, * Every 4 weeks until meningeal progression, or for a maximum of 4 months, * Then every 3 months beyond 4 months until meningeal progression.
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
Montpellier, France
RECRUITINGICM
Montpellier, France
RECRUITINGEstimation of the feasibility of the various blood tumoral biomarkers analysis
Success rate of the tested detection techniques. The success rate of a given detection technique is calculated by the ratio " detection success " / " number of screened patients"
Time frame: 4 YEARS
COHORT 1 and 2 : rate of patients with a grade 3-4 of neutropenia Ciclib-related
Number of participants with treatment-related neutropenia as assessed by CTCAE v4.03
Time frame: 4 YEARS
COHORT 1 and 2 : rate of patients with a hepatic toxicity Ciclib-related
Number of participants with treatment-related hepatic toxicity as assessed by CTCAE v4.03
Time frame: 4 YEARS
COHORT 3 : Correlation between response to immunotherapy (progressive versus non-progressive) and the number of circulating tumour cells (CTC) expressing the PDL1 marker at T1 (baseline)
Number of CTCs expressing PDL1 at T1
Time frame: 4 years
COHORT 4 : To compare the expression of the circulating MS9 mRNA biomarker between healthy subjects and treatment-naive patients with metastatic colorectal cancer
Expression of the MS9 mRNA biomarker
Time frame: 1 year
COHORT 5 : to study the impact of baseline HER2+ CTCs detection on PFS under T-DXd treatment
Progression-Free Survival (the primary outcome measure being the HR between CTC+ and CTC- patients, using the HER2+ CTC count at baseline)
Time frame: 4 years
COHORT 6 : To develop a computerised procedure for diagnosing glioma based on a nucleoside profile obtained by mass spectroscopy, using Artificial Intelligence
Positive predictive value and negative predictive value of the signature to discriminate glioma vs. no glioma
Time frame: 4 years
COHORT 7 : to optimise the culture of circulating tumour cells (CTCs)
Median number of CTCs 1 month after inclusion
Time frame: 4 years
COHORT 8 : to evaluate the concordance of CTC-AXL measurement (at inclusion) using the innovative EPIDROP technique and the CellSearch technique
Concordance rate of CTC-AXL measurement (at inclusion) by EPIDROP technique (AXL(-): 0 vs AXL(+): ≥1) and CellSearch technique (AXL(-): 0 vs AXL(+): ≥1)
Time frame: 4 years
COHORT 9 : to evaluate the predictive value of circulating immune populations for response to neo-adjuvant chemo-immunotherapy (according to pCR) in patients with early TNBCs, by performing an immunomonitoring before, during and after the treatment.
Response to treatment is defined as a pathological complete response (i.e. no residual invasive tumor in breast and axillary lymph nodes (ypT0ypN0)) after neo-adjuvant therapy.
Time frame: 4 years
COHORT 10 : to identify a new non-invasive biological test for the diagnosis of LPS by measuring MDM2 DNA in circulating vesicles
Sensibility and specificity of circulating MDM2 DNA in circulating vesicles for LPS diagnosis
Time frame: 4 years
COHORT 11 : to demonstrate a correlation between tumour progression under targeted therapy against EGFR (DEL19; L858R), KRAS G12C and the number of CTCs expressing the HES 1 marker at progression (T4)
Number of CTCs expressing HES 1 to T4
Time frame: 4 years
COHORT 12 : to assess the sensitivity of the hepcidin assay in blood for the diagnosis of leptomeningeal metastases of breast cancer, the gold standard being cytological examination of CSF (up to 3 samples).
Sensitivity of the hepcidin value in the 1st blood sample for the diagnosis of leptomeningeal metastases
Time frame: 4 years
COHORT 13 : to validate the stability of the RILA at 24hrs (D1), 48hrs (D2), 72hrs (D3) and 96hrs (D4)
The mean RILA at 24h (D1), 48h (D2), 72h (D3) and 96h (D4) will be compared. Equivalences between conditions ((1) 24h and 48h, (2) 24h and 72h, (3) 24h and 96h) will be assessed using Passing \& Bablok regression and/or paired t-test. Also, linear regressions between 24h, 48h, 72h and 96h for the same patients will be evaluated in order to determine, if necessary, a conversion formula.
Time frame: 1 year
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