Chemotherapy Monitoring by ctDNA in HER2- Metastatic Breast Cancer

NCT04720729 | Terminated Phase 2 DMC

• 1 other identifier: IC 2020-10
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

HER2-negative Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (7)

• L3C1 : ctDNA quantification

  ctDNA quantification (Mutant Allelic Frequency (MAF) %) during 3rd chemotherapy Line, 1st cycle (L3C1)

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

• L3C1 : ctDNA quantification

  ctDNA quantification (Mutant Allelic Frequency (MAF) %) during 3rd chemotherapy Line, 1st cycle (L3C1)

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

• L3C1 : chemotherapy efficacy

  ctDNA change : if major drop from D1 to D15 (MAF\>40%), no change on treatment. If no major drop from D1 to D15, change of chemotherapy

  ctDNA difference between Day 15 and Day 1

• LxC1 : ctDNA quantification

  ctDNA quantification (MAF %) during 4th chemotherapy line and following : Line x, 1st cycle (LxC1)

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

• LxC1 : ctDNA quantification

  ctDNA quantification (MAF %) during 4th chemotherapy line and following : Line x, 1st cycle (LxC1)

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

• LxC1 : chemotherapy efficacy

  ctDNA change : if major drop from D1 to D15 (MAF\>40%), no change on treatment recommanded If no major drop from D1 to D15, change of chemotherapy recommanded

  ctDNA difference between Day 15 and Day 1

• Progression Free Survival (PFS)

  Tumor assessment (MRI and/or CT) by RECIST 1.1

  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

Study Arms (1)

Single arm

EXPERIMENTAL

Patients with HER2-negative metastatic breast cancer, starting a second line of chemotherapy

Biological: Chemotherapy monitoring by circulating tumor DNA analysis

Interventions

Chemotherapy monitoring by circulating tumor DNA analysis BIOLOGICAL

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.

Single arm

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Breast cancer,
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 :
• 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

You may not qualify if:

• none

Sponsors & Collaborators

• Institut Curie: lead

Study Sites (1)

Institut Curie

Paris, 75005, France

Location

Study Officials

• François-Clément BIDARD, PR

  INSTITUT CURIE - Medical Oncology

  STUDY DIRECTOR

• Steven LE GOUILL, PR, MD

  INSTITUT CURIE - Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm phase 2 study, Chemotherapy monitoring based on ctDNA early changes

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: January 22, 2021
• Study Start: April 21, 2021
• Primary Completion: April 21, 2025
• Study Completion: April 21, 2025
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)