Clinical trial

Chemotherapy Monitoring by Circulating Tumor DNA (ctDNA) in HER2 (Human Epidermal Growth Factor Receptor-2)- Metastatic Breast Cancer (MONDRIAN): a Phase 2 Study

NCT04720729

Name

IC 2020-10

Description

This is a one-arm, single site, open-label phase II study. Patients will be enrolled in the screening step at the start of the second line of chemotherapy, and will undergo blood draws for ctDNA detection. Patients for whom ctDNA was successfully detected and found informative by the study executive board could then be included in the interventional step when starting a new line of therapy. ctDNA will be quantified using the customized test, at baseline and day 15 (+/- 3 working day) of cycle #1, and results will be made available before the cycle 2 Day 1, together with a treatment management recommendation by the Study Executive Board (continuation or discontinuation of the corresponding chemotherapy)

Trial arms

Trial start

2021-04-21

Estimated PCD

2026-10-01

Trial end

2026-10-01

Status

Recruiting

Phase

Early phase I

Treatment

Chemotherapy monitoring by circulating tumor DNA analysis

During the screening step (2nd chemotherapy line, cycle 1) : at each time point (L2C1D1 \& L2C1D15), 30 ml of blood will be drawn on special tubes with conservative suited for ctDNA analyses (e.g. STRECK® tubes).Then cell-free circulating DNA (cfcDNA) will be extracted from plasma following the manufacturer recommendations. cfcDNA will be quantified, and minimum 500-1000 copies will be analyzed by droplet digital PCR (ddPCR). Analyses will define if ctDNA could be detected during L2. For the interventional step, from L3 (3rd chemotherapy line) : 20 ml of blood will be drawn at L3C1D1 and L3C1D15. If ctDNA at D15 shows a major drop (\> 40%) from D1, treatment will be continued. If ctDNA at D15 shows no major drop from D1, chemotherapy will be changed.

Arms:

Single arm

Size

214

Primary endpoint

L3C1 : ctDNA quantification

At the Day 1 of Cycle 1 (each cycle is 21 days)

L3C1 : ctDNA quantification

At the Day 15 of Cycle 1 (each cycle is 21 days)

L3C1 : chemotherapy efficacy

ctDNA difference between Day 15 and Day 1

LxC1 : ctDNA quantification

At the Day 1 of the Cycle 1 (each cycle is 21 days)

LxC1 : ctDNA quantification

At the Day 15 of the Cycle 1 (each cycle is 21 days)

LxC1 : chemotherapy efficacy

ctDNA difference between Day 15 and Day 1

Progression Free Survival (PFS)

From date of inclusion until the date of first documented progression or date of death from any cause, whichever came first, assessed every 8-weeks up to 18 months

Eligibility criteria

Inclusion criteria : * Written informed consent * Woman ≥ 18 years old * Performance status 0-2 * Advanced HER2-negative metastatic breast cancer on the last tumor tissue assessed (ASCO-CAP (College of American Pathologists) guidelines) * Eligible to a second line of chemotherapy for MBC (Metastatic Breast Cancer) * Evaluable disease (per RECIST v1.1) * Organ functions compatible with the use of chemotherapies (as decided by the investigator) * No isolated CNS progression or leptomeningeal carcinomatosis * No concurrent stage IV malignancy * No concurrent severe and/or uncontrolled medical or psychological condition that would contraindicate participation in this study Additional criteria for the screening step : Presence of a known somatic mutation deemed trackable in circulating cell-free DNA. If the tumoral genetic landscape is unknown at inclusion, its characterization should be requested (or ongoing) at inclusion Additional criteria for the interventional step : * Satisfactory ctDNA detection and changes during the 2nd line, as determined by the Study Executive Board (SEB) * Patient eligible to a third line of chemotherapy Exclusion criteria : none

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Single arm phase 2 study, Chemotherapy monitoring based on ctDNA early changes', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 214, 'type': 'ESTIMATED'}}

Updated at

2024-06-10

1 organization

1 product

1 indication

Organization

Institut Curie

Product

Chemotherapy monitoring by circulating tumor DNA analysis

Indication

HER2-negative Metastatic Breast Cancer