Chemotherapy Monitoring by ctDNA in HER2- Metastatic Breast Cancer

Phase 2

Recruiting

• Conditions: HER2-negative Metastatic Breast Cancer
• Interventions: Biological: Chemotherapy monitoring by circulating tumor DNA analysis

• Registration Number: NCT04720729
• Lead Sponsor: Institut Curie

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)

Detailed Description

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:

That second line of treatment will be managed by clinical and radiological evaluations (RECIST); ctDNA will not be released to clinician and patient in real time.

While the included patient is being treated by second line therapy, a customized ctDNA detection based on tumor mutations (droplet-digital PCR) will be developed. Once set up, the two blood above-mentioned samples will be subjected to ctDNA detection. The SEB will then retrospectively assess whether ctDNA levels changes during the second line of treatment were indicative of the efficacy of the second line therapy. Patients for whom ctDNA was successfully detected and found informative by the SEB (Steering Executive Board) could then be included in the interventional step when starting a new line of therapy.

The third blood draw for ctDNA detection will be used to compare results to the tumor evaluation performed by imaging.

In the interventional step, ctDNA analyses and interpretation will be performed in real time; results made available before the cycle 2. Quantitative results will be interpreted by the laboratory committee, with two possible recommendations:

* ctDNA changes at day 15 display a major drop (Mutant Allelic Frequency (MAF) or copies/ml) reduced by 40% or more compared to baseline: continuing the same chemotherapy will be recommended;

* ctDNA changes at day 15 display no major drop (MAF or copies/ml) either increased, stable or reduced by less than 40% compared to baseline: changing chemotherapy will be recommended; In light of ctDNA levels changes observed during the second line for each included patient, the above-mentioned thresholds might be modified, on a case-by-case basis, by the SEB (to keep into account individual characteristics).

The test will be repeated for any new line of therapy that may be initiated during the first 6 months following the accrual of each patient in the interventional step. If this strategy is considered efficient (on an individual basis), further ctDNA tests will be made available on request for the next six months. Consequently, the patients who will change chemotherapy line after the recommendation following result from C1D15 ctDNA results will have a new ctDNA test at C1D1 and C1D15 of the new chemotherapy line.

Study Timeline

• Study First Submitted: 2021-01-12
• Study First Submitted QC: 2021-01-20
• Study First Posted: 2021-01-22
• Study Start: 2021-04-21
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-07
• Last Update Posted: 2024-06-10
• Primary Completion: 2026-10
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 214

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single arm	Chemotherapy monitoring by circulating tumor DNA analysis	Patients with HER2-negative metastatic breast cancer, starting a second line of chemotherapy

Primary Outcome Measures

Name	Time	Method
LxC1 : chemotherapy efficacy	ctDNA difference between Day 15 and Day 1	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
LxC1 : ctDNA quantification	At the Day 15 of the Cycle 1 (each cycle is 21 days)	ctDNA quantification (MAF %) during 4th chemotherapy line and following : Line x, 1st cycle (LxC1)
L3C1 : ctDNA quantification	At the Day 15 of Cycle 1 (each cycle is 21 days)	ctDNA quantification (Mutant Allelic Frequency (MAF) %) during 3rd chemotherapy Line, 1st cycle (L3C1)
L3C1 : chemotherapy efficacy	ctDNA difference between Day 15 and Day 1	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
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	Tumor assessment (MRI and/or CT) by RECIST 1.1

Trial Locations

Locations (1)

Institut Curie; 🇫🇷 Paris, France