Analysis of Circulating Tumor Markers in Blood

Overview

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).

Interventions

• Biological Blood sampling
  blood sampling time : cycle 1 day 15 and cycle 2 day 15 : one sample (6ml) by time
• Biological Blood sampling C3
  Blood samples will be collected at four key time points: * baseline (T1), * first scan assessment (T2), * second scan assessment (T3), * and progression (T4).
• Biological Blood sampling C4/7/10/13
  Blood samples will be collected before any treatment
• Biological Blood sampling C5
  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)
• Biological Blood sampling C6
  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).
• Biological Blood sampling C8
  Blood samples will be collected at five key time points: * At the inclusion * At follow-up visit 2 to 6, every 3 months
• Biological Blood sampling C9
  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
• Biological Blood sampling C11 + FFPE
  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
• Biological Blood sampling C12
  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.

Primary outcome measures

• Estimation of the feasibility of the various blood tumoral biomarkers analysis [Time frame: 4 YEARS]

Secondary outcome measures (12)

• COHORT 1 and 2 : rate of patients with a grade 3-4 of neutropenia Ciclib-related [Time frame: 4 YEARS]
• COHORT 1 and 2 : rate of patients with a hepatic toxicity Ciclib-related [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) [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 [Time frame: 1 year]
• COHORT 5 : to study the impact of baseline HER2+ CTCs detection on PFS under T-DXd treatment [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 [Time frame: 4 years]
• COHORT 7 : to optimise the culture of circulating tumour cells (CTCs) [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 [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. [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 [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) [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). [Time frame: 4 years]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

France · 2 centers

• Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle — Montpellier
• ICM — Montpellier

Publications

• Bardol T, Eslami-S Z, Masmoudi D, Alexandre M, Duboys de Labarre M, Bobrie A, D'Hondt V, Guiu S, Kurma K, Cayrefourcq L, Jacot W, Alix-Panabieres C. First evidence of AXL expression on circulating tumor cells in metastatic breast cancer patients: A proof-of-concept study. Cancer Med. 2024 Jan;13(1):e6843. doi: 10.1002/cam4.6843. Epub 2023 Dec 22. PMID 38132919
• Leenhardt F, Fiteni F, Gauthier L, Alexandre M, Guiu S, Firmin N, Pouderoux S, Viala M, Lossaint G, Gautier C, Mollevi C, Gracia M, Gongora C, Mbatchi L, Evrard A, Jacot W. Pharmacokinetic Variability Drives Palbociclib-Induced Neutropenia in Metastatic Breast Cancer Patients: Drug-Drug Interactions Are the Usual Suspects. Pharmaceutics. 2022 Apr 11;14(4):841. doi: 10.3390/pharmaceutics14040841. PMID 35456675
• Leenhardt F, Alexandre M, Guiu S, Pouderoux S, Beaujouin M, Lossaint G, Philibert L, Evrard A, Jacot W. Impact of pharmacist consultation at clinical trial inclusion: an effective way to reduce drug-drug interactions with oral targeted therapy. Cancer Chemother Pharmacol. 2021 Oct;88(4):723-729. doi: 10.1007/s00280-021-04331-0. Epub 2021 Jul 20. PMID 34286354
• Leenhardt F, Gracia M, Perrin C, Muracciole-Bich C, Marion B, Roques C, Alexandre M, Firmin N, Pouderoux S, Mbatchi L, Gongora C, Jacot W, Evrard A. Liquid chromatography-tandem mass spectrometric assay for the quantification of CDK4/6 inhibitors in human plasma in a clinical context of drug-drug interaction. J Pharm Biomed Anal. 2020 Sep 5;188:113438. doi: 10.1016/j.jpba.2020.113438. Epub 2020 Ju PMID 32623316
• Leenhardt F, Jacot W, Lellouche L, Guiu S, Viala M, Firmin N, Payen A, Mbatchi LC, Fiteni F, Evrard A. Antacid co-treatment and pregnane X receptor genetic polymorphisms are survival determinants in patients treated with palbociclib. Breast Cancer Res Treat. 2026 Jul 28;218(2):20. doi: 10.1007/s10549-026-08041-0. PMID 42521839
• Kurma K, Bardol T, Mollevi C, Eslami-S Z, Garima F, Alexandre M, Bobrie A, Lossaint G, Massemin B, D'Hondt V, Guiu S, Cayrefourcq L, Jacot W, Alix-Panabieres C. Liquid biopsy reveals the immune status and protein profiles linked to CTC burden and clinical outcomes in metastatic breast cancer. J Exp Clin Cancer Res. 2026 Apr 18;45(1):111. doi: 10.1186/s13046-026-03709-3. PMID 42001180

Identifiers

NCT: NCT04025541 · PROICM 2017-05 BAL

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗