HER2-negative Metastatic Breast CancerPhase 2MONDRIANNCT04720729
Chemotherapy Monitoring by ctDNA in HER2- Metastatic Breast Cancer
A Phase 2 study testing Chemotherapy monitoring by circulating tumor DNA analysis in people with HER2-negative Metastatic Breast Cancer, run by Institut Curie at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- HER2-negative Metastatic Breast Cancer
- What is being tested?
- Chemotherapy monitoring by circulating tumor DNA analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteFrance
- Study dates
- 21 Apr 2021to 21 Apr 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- none
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Chemotherapy Monitoring by Circulating Tumor DNA (ctDNA) in HER2 (Human Epidermal Growth Factor Receptor-2)- Metastatic Breast Cancer (MONDRIAN): a Phase 2 Study
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)
Read the 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.
- Conditions
- HER2-negative Metastatic Breast Cancer
- Being tested
- Chemotherapy monitoring by circulating tumor DNA analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chemotherapy monitoring by circulating tumor DNA analysisBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Patients with HER2-negative metastatic breast cancer, starting a second line of chemotherapy Receives: Biological: Chemotherapy monitoring by circulating tumor DNA analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
L3C1 : ctDNA quantification
ctDNA quantification (Mutant Allelic Frequency (MAF) %) during 3rd chemotherapy Line, 1st cycle (L3C1)
Measured: 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)
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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
Measured: ctDNA difference between Day 15 and Day 1
Progression Free Survival (PFS)
Tumor assessment (MRI and/or CT) by RECIST 1.1
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2021
- Study start21 Apr 2021
- Primary completion21 Apr 2025
- Study completion21 Apr 2025
Why it stopped: insufficient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-negative Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm phase 2 study, Chemotherapy monitoring based on ctDNA early changes
- Masking
- None (open label)
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Curie
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- François-Clément BIDARD, PR, Study director, INSTITUT CURIE - Medical OncologySteven LE GOUILL, PR, MD, Study chair, INSTITUT CURIE - Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04720729
- Sponsor's protocol ID
- IC 2020-10
- Acronym
- MONDRIAN
- Status last verified
- Jun 2025
- First submitted
- 12 Jan 2021
- Last updated
- 22 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chemotherapy Monitoring by Circulating Tumor DNA (ctDNA) in HER2 (Human Epidermal Growth Factor Receptor-2)- Metastatic Breast Cancer (MONDRIAN): a Phase 2 Study
- ClinicalTrials.gov ID
- NCT04720729
- Acronym / sponsor ID
- MONDRIAN / IC 2020-10
- Conditions
- HER2-negative Metastatic Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient recruitment
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Institut CurieUniversity, hospital or other
- Study start
- 21 Apr 2021 (actual)
- Primary completion
- 21 Apr 2025 (actual)
- Study completion
- 21 Apr 2025 (actual)
- First posted
- 22 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm phase 2 study, Chemotherapy monitoring based on ctDNA early changes
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Biological: Chemotherapy monitoring by circulating tumor DNA analysisPatients with HER2-negative metastatic breast cancer, starting a second line of chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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)
Key exclusion criteria (1 listed)
- none
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chemotherapy monitoring by circulating tumor DNA analysisDuring 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. | Biological | Single arm |
Primary outcome
L3C1 : ctDNA quantification
Time frame: At the Day 1 of Cycle 1 (each cycle is 21 days)
ctDNA quantification (Mutant Allelic Frequency (MAF) %) during 3rd chemotherapy Line, 1st cycle (L3C1)
L3C1 : ctDNA quantification
Time frame: 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
Time frame: 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
LxC1 : ctDNA quantification
Time frame: At the Day 1 of the Cycle 1 (each cycle is 21 days)
ctDNA quantification (MAF %) during 4th chemotherapy line and following : Line x, 1st cycle (LxC1)
LxC1 : ctDNA quantification
Time frame: 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)
LxC1 : chemotherapy efficacy
Time frame: 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
Progression Free Survival (PFS)
Time frame: 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
Results and safety
The study was stopped early (reason given: insufficient recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
François-Clément BIDARD, PR study director
INSTITUT CURIE - Medical Oncology
Steven LE GOUILL, PR, MD study chair
INSTITUT CURIE - Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Chemotherapy monitoring by circulating tumor DNA analysis in people with HER2-negative Metastatic Breast Cancer, run by Institut Curie at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: insufficient recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
L3C1 : ctDNA quantification (time frame: At the Day 1 of Cycle 1 (each cycle is 21 days)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2025.