Analysis of Circulating Tumor Markers in Blood (ALCINA2)

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.

Study Overview

• Status: Recruiting
• Conditions: Glioma; Sarcoma; Cancer; Breast Cancer; Colon Cancer; Lung Cancers
• Intervention / Treatment: 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

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 Type: Interventional
• Enrollment (Estimated): 992
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: texier emmannuelle; Phone Number: 0467613102; Email: emmanuelle.texier@icm.unicancer.fr

Study Locations

• France
  • Montpellier, France, 34298
    • Recruiting
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
    • Contact: Marc Ychou, MD, PhD; Phone Number: 33-4-6761-3066; Email: mychou@valdorel.fnclcc.fr
    • Contact: Aurore MOUSSION; Phone Number: +33 0467613102; Email: aurore.moussion@icm.unicancer.fr
  • Montpellier, France, 34298
    • Recruiting
    • ICM
    • Contact: WILLIAM JACOT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: COHORT 1 BREAST TUMOR/PALBOCICLIB; Patient with a locally Advanced tumor or metastatic tumor RH+/HER 2 - , treated by palbociclib BLOOD SAMPLING	Biological: Blood sampling; blood sampling time : cycle 1 day 15 and cycle 2 day 15 : one sample (6ml) by time; Other Names: Tumor sampling
Other: COHORT 2 BREAST TUMOR / RIBOCICLIB; Patient with a locally Advanced tumor or metastatic tumor RH+/HER 2 - , treated by ribociclib BLOOD SAMPLING	Biological: Blood sampling; blood sampling time : cycle 1 day 15 and cycle 2 day 15 : one sample (6ml) by time; Other Names: Tumor sampling
Other: COHORT 3 - LUNG CANCER; Patients with histologically proven metastatic bronchial carcinoma eligible for immunotherapy	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).
Other: COHORT 4 - CCRm; Patient with metastatic colorectal adenocarcinoma	Biological: Blood sampling C4/7/10/13; Blood samples will be collected before any treatment
Other: COHORT 5 - T-DXd; Patient with HER2 + metastatic breast cancer, requiring treatment with T-DXd	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)
Other: COHORT 6 - Glioma; Patient with grade II, III or IV diffuse glioma	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).
Other: COHORT 7 - CIRCUS 2; Patients with non-metastatic colon cancer	Biological: Blood sampling C4/7/10/13; Blood samples will be collected before any treatment
Other: COHORT 8 - CTC-AXL Breast; Patients with treatment-naive metastatic breast cancer with distant metastases	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
Other: COHORT 9 - ImmunoTNBC; Patients newly diagnosed with non-metastatic stage II - III early TNBC, requiring neoadjuvant treatment and previously untreated.	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
Other: COHORT 10 - LPS; Patients with well differentiated (WD) liposarcoma, dedifferentiated (DD) liposarcoma or sarcoma other than liposarcoma	Biological: Blood sampling C4/7/10/13; Blood samples will be collected before any treatment
Other: COHORT 11 - LUNG DRIVER; Patients with Metastatic bronchial carcinoma activating alterations in EGFR (del 19; L858R) or KRAS G12C	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
Other: COHORT 12 - LMD; Patient with breast cancer and suspected with leptomeningeal metastases	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.
Other: COHORT 13 - RILA STAB; Patients with breast cancer requiring radiotherapy, whatever the tumor stage	Biological: Blood sampling C4/7/10/13; Blood samples will be collected before any treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimation 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"	4 YEARS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	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)	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	4 years
COHORT 7 : to optimise the culture of circulating tumour cells (CTCs)	Median number of CTCs 1 month after inclusion	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)	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.	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	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	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	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.	1 year

Collaborators and Investigators

• Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle

Publications and helpful links

General 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.
• 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.
• 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.
• 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 Jun 22.

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2018
• Primary Completion (Estimated): May 29, 2026
• Study Completion (Estimated): May 29, 2029

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 19, 2019

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Neoplasms, Connective and Soft Tissue; Colonic Neoplasms; Sarcoma
• Other Study ID Numbers: PROICM 2017-05 BAL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No