Analysis of Circulating Tumor mArkers in Blood 4 - ALCINA 4

NCT05088395 | Recruiting

• 1 other identifier: IC 2020-11
• Study Type: interventional
• Target: 2,050
• Locations: 1 country
• Sites: 2

Brief Summary

Multi-cohort exploratory prospective study. Participation in the ALCINA 4 study does not change the standard management of the patient, including the treatments administered. A sampling schedule will be set up for each cohort. Depending on the clinical context studied and the biomarkers studied and/or sought, the timing of blood samples will vary between cohorts. There may be up to 4 samples (or more) taken per patient for up to 18, 24 or 36 months. If a specific tumor sample is required, it will be collected only once during the study.

Conditions

Cancer

Keywords

circulating biomarkers; Cohort

Outcome Measures

Primary Outcomes (15)

• Detection rate of circulating biomarkers in cohort 1

  Positivity rate of the detection technique (in %)

  Baseline

• Detection rate of circulating biomarkers in cohort 2

  Positivity rate of the detection technique (in %)

  Baseline

• Detection rate of circulating biomarkers in cohort 2

  Positivity rate of the detection technique (in %)

  Before treatment

• Detection rate of circulating biomarkers in cohort 2

  Positivity rate of the detection technique (in %)

  At 3 weeks of treatment

• Detection rate of circulating biomarkers in cohort 2

  Positivity rate of the detection technique (in %)

  At 9 weeks of treatment

• Detection rate of circulating biomarkers in cohort 2

  Positivity rate of the detection technique (in %)

  At disease progression

• Detection rate of circulating biomarkers in cohort 1

  Positivity rate of the detection technique (in %)

  Before surgery

• Detection rate of circulating biomarkers in cohort 1

  Positivity rate of the detection technique (in %)

  After surgery (from 3 to 5 weeks)

• Detection rate of circulating biomarkers in cohort 1

  Positivity rate of the detection technique (in %)

  After surgery (from 2 to 3 months)

• Detection rate of circulating biomarkers in cohort 3

  Positivity rate of the detection technique (in %)

  Baseline

• Detection rate of circulating biomarkers in cohort 3

  Positivity rate of the detection technique (in %)

  At the end of cycle 1 (each cycle is 21 days)

• Detection rate of circulating biomarkers in cohort 3

  Positivity rate of the detection technique (in %)

  After surgery (from 2 to 3 months)

• Detection rate of circulating biomarkers in cohort 3

  Positivity rate of the detection technique (in %)

  At disease progression

• Detection rate of circulating biomarkers in cohort 4

  Positivity rate of the detection technique (in %)

  At pre-surgery or before starting treatment

• Detection rate of circulating biomarkers in cohort 4

  Positivity rate of the detection technique (in %)

  At 6 weeks after surgery or after start of treatment

Study Arms (12)

Cohort 1: "SENOLOC"

OTHER

Detecting residual disease after surgery is absolutely crucial in oncology, as this detection could allow the personalisation of post-operative treatments based on the presence of residual disease. The laboratory wishes to develop a new technique for the detection of circulating tumour DNA, based on the recognition of translocation fragments in circulating DNA by shallow whole genome sequencing. This is an original approach, which to our knowledge has not been tested so far with the envisaged bioinformatics approach and could potentially be more sensitive than the techniques currently used to detect residual disease after surgical removal of localised (non-metastatic) breast cancer. The analysis will therefore focus on the search for tumour chromosomal translocations, which will need to be differentiated from possible germline chromosomal translocations. The collection of constitutional DNA is therefore planned in this cohort.

Other: Blood sample

Cohort 2: "Immuno-TNBC "

OTHER

The aim for this cohort is to study the role that variations in circulating tumour DNA might have as a marker associated with response during chemoimmunotherapy. A fresh biopsy (subsequently stored frozen) is required for mutational profiling analysis (which will be used to track circulating tumour DNA in the blood). In addition, it will be used to analyse currently recognised biological tissue factors of response to chemoimmunotherapy (PD-L1 labelling, mutational load, ...) and to identify possible associations with circulating tumour DNA variations. Constitutional DNA analysis is necessary for the determination of point mutations present in the tumour (to be differentiated from polymorphisms present at the constitutional level), as the determination of these mutations is essential to monitor circulating tumour DNA and will therefore be collected.

Other: Blood sample; Other: Biopsy

Cohort 3: "Trans-TNBC"

OTHER

The objective of this cohort is the development of new plasma tests, for example based on the detection of chromosomal translocations of circulating tumor DNA. The hypothesis is that these tests would allow the detection of relapse, the prediction of treatment efficacy and the monitoring of treatment efficacy at different stages of cancer in patients with triple-negative breast cancer, either in the non-metastatic phase with planned neo-adjuvant treatment, or in the metastatic phase. The number of inclusions between these 2 populations (neo-adjuvant and metastatic) will be monitored at the operational level to avoid an excessive imbalance towards one group.

Other: Blood sample

Cohort 4: "Treg"

OTHER

The purpose of this cohort, based on the previous results, is to: 1. quantify the expression level of target genes on tumor Regulatory T (Tregs) at the protein level, 2. perform multiparametric FACS analysis on blood and tumor samples from patients treated at the Institut Curie, with breast or ovary cancer and to understand the potential of these targets as biomarkers of disease. In the context of this ALCINA-4 cohort n°4, for breast and ovary patients, 40 ml of blood will be collected and tumor fragments obtained from surgery (50 breast patients) or therapeutically required biopsy (30 ovary patients). No additional biopsy than the ones belonging to the therapeutic process will be performed in this protocol. Biopsies performed as part of standard of care will be used if sufficient material is available.

Other: Blood sample; Other: Biopsy

Cohort 5: "Pembro Neo"

OTHER

The purpose of this cohort is to determine the detection rate of circulating tumour DNA (ctDNA) before and after surgery in the blood of patients who received neoadjuvant treatment with chemoimmunotherapy for early triple-negative breast cancer (TNBC). There will be two subgroups : patients who have not yet started neoadjuvant treatment (subcohort 1) and patients who have already started neoadjuvant treatment (subcohort 2). Biopsy of a tumour lesion will be performed before the start of neoadjuvant treatment (only for subcohort 1). The collection of constitutional DNA, plasma and circulating tumour DNA are planned in this cohort at different time points.

Other: Blood sample; Other: Biopsy

Cohort 6: "THL"

OTHER

The main objective of this exploratory cohort is to characterize the detection rate of ctDNA before and during therapy with T-DXd (Trastuzumab deruxtecan) for patients with HER2-low metastatic breast cancer, requiring treatment with T-DXd. Tumor biopsy will be performed after inclusion and before the start of treatment on cycle 1 day 1 for at least 30 patients. The collection of constitutional DNA, is planned in this cohort at different time points : T1 and T2 (before treatment start) are critical to evaluate the intra-patient reproducibility of liquid biomarkers. T3 will investigate the response to therapy while T4 will focus on resistance mechanisms.

Other: Blood sample; Other: Biopsy

Cohort 7:"CDK4/6 adjuvant"

OTHER

The purpose of this cohort is to determine the prognostic impact of circulating tumor DNA detection and monitoring in patients receiving a CDK4/6 inhibitor in adjuvant breast cancer. 50 ml of blood will be collected in EDTA tubes for constitutional DNA and plasma for research of circulating biomarkers at different time points (4 time points).

Other: Blood sample

Cohort 8:"ctDNA adjuvant "

OTHER

The purpose of this cohort is to estimate the incidence of ctDNA detection in patients with early-stage breast cancer during follow-up to detect metastatic relapse earlier in asymptomatic patients. ctDNA analysis will be performed using various techniques, including next-generation sequencing (NGS), with or without analysis of tumor tissue, taken as part of the standard care. 40 ml of blood samples will be collected at four time points: * enrollment, * 6 months (+/- 15 days), * 12 months (+/- 15 days), * 18 months (+/- 15 days) after inclusion.

Other: Blood sample; Other: Biopsy

Cohort 9:"ADN-CIRC-Poumon "

OTHER

The purpose of this cohort is to: * Generate data on the levels and nature of circulating tumor DNA under chemo-immunotherapy. * Monitor the evolution of the circulating immune response under systemic chemo-immunotherapy. Tumor biopsy will be performed after inclusion and before the start of treatment. 50 ml of blood samples will be collected at four time points: * At inclusion, before starting neoadjuvant treatment * At the start of cycle 3 (C3J1) of neoadjuvant treatment * At the time of surgery (after neoadjuvant treatment) * At the start of monitoring, i.e. 3 months (+/- 1 month) after surgery.

Other: Blood sample; Other: Biopsy

Cohort 10: "UM TENEO"

OTHER

The purpose of this cohort is to : * Evaluate recurrence-free survival (RFS) after R0/R1 surgery * Assess effectiveness of Tebentafusp associated with surgery for patients with uveal melanoma metastases. 3 sub-cohorts : * Sub-cohort 1: HLA-A\*02:01-positive patients, eligible for R0 surgery and Tebentafusp (n=20) * Sub-cohort 2: HLA-A\*02:01-negative patients, eligible for R0 surgery and immunotherapy at next relapse (n=20) * Sub-cohort 3: HLA-A\*02:01 positive patients, not eligible for R0 surgery but eligible for Tebentafusp (n=20). Tumor biopsy will be performed during surgery (sub-cohorts n°1 and 2) or after inclusion (sub-cohort n°3). 40 ml of blood will be collected in EDTA tubes for constitutional DNA and circulating DNA in plasma for research of biomarkers at 4 time points.

Other: Blood sample; Other: Biopsy

Cohort 11: L1 CDK4/6

OTHER

The purpose of this cohort is to : * Characterize the kinetics of ctDNA during treatment with a CDK4/6 inhibitor. * Study the links between ctDNA and common serum markers. * Study the links between ctDNA and markers derived from metabolic imaging. 40 to 50 ml of blood will be collected in STRECK tubes for constitutional DNA and circulating DNA in plasma for research of biomarkers at different time points.

Other: Blood sample

Cohort 12: PDX

OTHER

The purpose of this cohort is to correlate the circulating biomarkers with molecular analysis of patients-derived xenografts (PDX) established from breast cancers. 10 ml of blood will be collected in EDTA tubes for constitutional DNA at inclusion. Tumor tissue samples (for PDX) will be taken at inclusion for PDX establishment.

Other: Blood sample; Other: Biopsy

Interventions

Blood sample OTHER

Depending on the clinical context studied and the biomarkers studied and/or sought, the timing of blood samples will vary between cohorts. There may be up to 4 samples (or more) taken per patient for up to 18, 24 or 36 months according to the cohorts.

Cohort 10: "UM TENEO"; Cohort 11: L1 CDK4/6; Cohort 12: PDX; Cohort 1: "SENOLOC"; Cohort 2: "Immuno-TNBC "; Cohort 3: "Trans-TNBC"; Cohort 4: "Treg"; Cohort 5: "Pembro Neo"; Cohort 6: "THL"; Cohort 7:"CDK4/6 adjuvant"; Cohort 8:"ctDNA adjuvant "; Cohort 9:"ADN-CIRC-Poumon "

Biopsy OTHER

If a specific tumor sample is required, it will be collected only once during the study

Cohort 10: "UM TENEO"; Cohort 12: PDX; Cohort 2: "Immuno-TNBC "; Cohort 4: "Treg"; Cohort 5: "Pembro Neo"; Cohort 6: "THL"; Cohort 8:"ctDNA adjuvant "; Cohort 9:"ADN-CIRC-Poumon "

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient treated for cancer at one of the participating center
• years old or higher
• Signed informed consent form
• Patient not deprived of their liberty or under guardianship (including temporary guardianship)
• Patient covered by social security scheme
• Patient with no compliance issue (related to geographical, social or psychological reasons) for study follow up
• Other additional criteria will be defined (defining tumor type and clinical setting), by cohort
• If a biopsy tumor sample is to be taken:
• Tumor considered as accessible by biopsy (at the investigator's discretion).
• Normal blood coagulation tests (if applicable, and in case of a non-superficial tumor lesion).
• No anticoagulant or antiaggregant treatment for the biopsy.

You may not qualify if:

• Pregnant and/or breast-feeding women depending on cohort.

Sponsors & Collaborators

• Institut Curie: lead

Study Sites (2)

Institut Curie

Paris, 75005, France

RECRUITING

Institut Curie

Saint-Cloud, 92210, France

RECRUITING

MeSH Terms

Conditions

Neoplasms

Interventions

Blood Specimen Collection; Biopsy

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical

Study Officials

• Francois-Clement BIDARD

  Institut Curie

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie-Emmanuelle LEGRIER

CONTACT

0033156245649; drci.promotion@curie.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Interventional study (blood collections and possibly tumor sample collection depending on cohort type) on single group cohorts (each cohort is defined in the arms below). Detection study of blood tumor biomarkers and correlation with clinicopathological characteristics.

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: October 21, 2021
• Study Start: May 19, 2022
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

Locations

FR (2)