Analysis of Circulating Tumor Markers in Blood

Not Applicable

Recruiting

• Conditions: Cancer; Breast Cancer; Sarcoma; Lung Cancers; Colon Cancer; Glioma
• Interventions: Biological: Blood sampling; Biological: Blood sampling C3; Biological: Blood sampling C4/7/10/13; Biological: Blood sampling C5; Biological: Blood sampling C6; Biological: Blood sampling C8; Biological: Blood sampling C9; Biological: Blood sampling C11 + FFPE; Biological: Blood sampling C12

• Registration Number: NCT04025541
• Lead Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle

Brief Summary

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.

Detailed Description

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 Timeline

• Study Start: 2018-05-29
• Study First Submitted: 2019-06-05
• Study First Submitted QC: 2019-07-16
• Study First Posted: 2019-07-19
• Status Verified: 2025-02
• Last Update Submitted: 2025-03-27
• Last Update Posted: 2025-04-02
• Primary Completion: 2026-05-29
• Study Completion: 2029-05-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 992

Inclusion Criteria

1. Patient presenting an invasive tumoral pathology (proved or suspected), whatever is the location or the stage,
2. Man or woman ≥ 18 years,
3. Obtaining of the informed consent signed before any procedure of specific preselection on approval.

Exclusion Criteria

1. Private persons of freedom or under guardianship,
2. Patient whose regular follow-up is impossible for psychological, family, social or geographical reasons,
3. Pregnant woman and/or breast-feeding,
4. Unaffiliated patient to Social Protection System,

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
COHORT 1 BREAST TUMOR/PALBOCICLIB	Blood sampling	Patient with a locally Advanced tumor or metastatic tumor RH+/HER 2 - , treated by palbociclib BLOOD SAMPLING
COHORT 2 BREAST TUMOR / RIBOCICLIB	Blood sampling	Patient with a locally Advanced tumor or metastatic tumor RH+/HER 2 - , treated by ribociclib BLOOD SAMPLING
COHORT 3 - LUNG CANCER	Blood sampling C3	Patients with histologically proven metastatic bronchial carcinoma eligible for immunotherapy
COHORT 4 - CCRm	Blood sampling C4/7/10/13	Patient with metastatic colorectal adenocarcinoma
COHORT 5 - T-DXd	Blood sampling C5	Patient with HER2 + metastatic breast cancer, requiring treatment with T-DXd
COHORT 6 - Glioma	Blood sampling C6	Patient with grade II, III or IV diffuse glioma
COHORT 7 - CIRCUS 2	Blood sampling C4/7/10/13	Patients with non-metastatic colon cancer
COHORT 8 - CTC-AXL Breast	Blood sampling C8	Patients with treatment-naive metastatic breast cancer with distant metastases
COHORT 9 - ImmunoTNBC	Blood sampling C9	Patients newly diagnosed with non-metastatic stage II - III early TNBC, requiring neoadjuvant treatment and previously untreated.
COHORT 10 - LPS	Blood sampling C4/7/10/13	Patients with well differentiated (WD) liposarcoma, dedifferentiated (DD) liposarcoma or sarcoma other than liposarcoma
COHORT 11 - LUNG DRIVER	Blood sampling C11 + FFPE	Patients with Metastatic bronchial carcinoma activating alterations in EGFR (del 19; L858R) or KRAS G12C
COHORT 12 - LMD	Blood sampling C12	Patient with breast cancer and suspected with leptomeningeal metastases
COHORT 13 - RILA STAB	Blood sampling C4/7/10/13	Patients with breast cancer requiring radiotherapy, whatever the tumor stage

Primary Outcome Measures

Name	Time	Method
Estimation of the feasibility of the various blood tumoral biomarkers analysis	4 YEARS	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"

Secondary Outcome Measures

Name	Time	Method
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.	4 years	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.
COHORT 10 : to identify a new non-invasive biological test for the diagnosis of LPS by measuring MDM2 DNA in circulating vesicles	4 years	Sensibility and specificity of circulating MDM2 DNA in circulating vesicles for LPS diagnosis
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)	4 years	Number of CTCs expressing HES 1 to T4
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).	4 years	Sensitivity of the hepcidin value in the 1st blood sample for the diagnosis of leptomeningeal metastases
COHORT 13 : to validate the stability of the RILA at 24hrs (D1), 48hrs (D2), 72hrs (D3) and 96hrs (D4)	1 year	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.
COHORT 1 and 2 : rate of patients with a grade 3-4 of neutropenia Ciclib-related	4 YEARS	Number of participants with treatment-related neutropenia as assessed by CTCAE v4.03
COHORT 1 and 2 : rate of patients with a hepatic toxicity Ciclib-related	4 YEARS	Number of participants with treatment-related hepatic toxicity as assessed by CTCAE v4.03
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)	4 years	Number of CTCs expressing PDL1 at T1
COHORT 4 : To compare the expression of the circulating MS9 mRNA biomarker between healthy subjects and treatment-naive patients with metastatic colorectal cancer	1 year	Expression of the MS9 mRNA biomarker
COHORT 5 : to study the impact of baseline HER2+ CTCs detection on PFS under T-DXd treatment	4 years	Progression-Free Survival (the primary outcome measure being the HR between CTC+ and CTC- patients, using the HER2+ CTC count at baseline)
COHORT 6 : To develop a computerised procedure for diagnosing glioma based on a nucleoside profile obtained by mass spectroscopy, using Artificial Intelligence	4 years	Positive predictive value and negative predictive value of the signature to discriminate glioma vs. no glioma
COHORT 7 : to optimise the culture of circulating tumour cells (CTCs)	4 years	Median number of CTCs 1 month after inclusion
COHORT 8 : to evaluate the concordance of CTC-AXL measurement (at inclusion) using the innovative EPIDROP technique and the CellSearch technique	4 years	Concordance rate of CTC-AXL measurement (at inclusion) by EPIDROP technique (AXL(-): 0 vs AXL(+): ≥1) and CellSearch technique (AXL(-): 0 vs AXL(+): ≥1)

Trial Locations

Locations (2)

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle; 🇫🇷 Montpellier, France

ICM; 🇫🇷 Montpellier, France