Metastatic Breast CancerGIM21NCT05735392

Liquid Biopsy: Intercepting Mutational Trajectories of HER2 (Human Epidermal Growth Factor Receptor 2) Breast Cancer (GIM21 Trial)

A study testing Both blood and tissues collection for patients with metastatic breast cancer HER2+ pretreated with no more than one line of anti-HER2 therapy for advanced breast cancer. in people with Metastatic Breast Cancer, run by Consorzio Oncotech at 9 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is an open, interventional, non-pharmacological, prospective study. Patients will receive trastuzumab emtansine (T-DM1) at 3.6 mg/kg intravenously every 21 days, as per Summary of Product Characteristics (SmPC). This is a no-profit study. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Metastatic Breast Cancer
What is being tested?: Both blood and tissues collection for patients with metastatic breast cancer HER2+ pretreated with no more than one line of anti-HER2 therapy for advanced breast cancer.
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 48 participants
Where: 9 sitesItaly
Study dates: 7 Nov 2018to 12 Jan 2022
Phase: Interventional
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

Male and female patients with a documented diagnosis of metastatic HER2-positive breast cancer (BC) as defined by an immunohistochemistry (IHC) score of 3+, alternatively score 2+ and HER2 amplification ratio ≥ 2.0
All patients eligible to treatment with T-DM1, according to SmPC previously treated with a taxane and trastuzumab. Patients who previously underwent first-line treatment with an association of TTZ with PTZ are also eligible. No more than one line of anti-HER2 treatment for advanced disease are allowed.
Available tissue from the primary tumor. If possible, newly obtained core or excisional biopsy on metastatic site at baseline (this biopsy won't impact on timing for patient enrollment and not leading to patient exclusion). High quality genomic DNA from the above for NGS mutational analysis.
Patients with both measurable and non-measurable disease (according to modified RECIST 1.1 criteria) are eligible.
18 years of age on day of signing informed consent.
a left ventricular ejection fraction of 50% or more (determined by echocardiography or multiple-gated acquisition [MUGA] scanning);

Show all 15Show fewer

an Eastern Cooperative Oncology Group performance status of 0 or 1.
Adequate organ function (obtained within 14 days prior to treatment study) as evidenced by:
Absolute neutrophil count (ANC) 1.5 X 109/L without myeloid growth factor support for 7 days preceding the lab assessment;
Haemoglobin (Hgb) 9 g/dL (90 g/L); < 9 g/dL (< 90 g/L) is acceptable if hemoglobin is corrected to 9 g/dL (90 g/L) ;
Platelet count 75 X 109/L without blood transfusions for 7 days preceding the lab assessment;
Bilirubin 1.5 X upper limit of normal (ULN), except for patients with a documented history of Gilbert's disease;
Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) 2.5 X ULN (for patients with liver metastases 5 X ULN);
Life expectancy > 12 weeks;
Written informed consent obtained before any screening procedure and according to local guidelines.

Who cannot join

Prior treatment with T-DM1.
Symptomatic central nervous system (CNS) metastases, or treatment for these metastases within the 2 months preceding enrollment.
Current participation in study therapy, or previous participation in a study involving the administration of an investigational agent within 4 weeks of administration of the first dose of treatment.
History of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment; a history of myocardial infarction or unstable angina within 6 months before.
Female patients who are pregnant or lactating, who plan to get pregnant, or who have a positive serum pregnancy test prior to first dose of study treatment.
Prior malignancy (other than breast cancer) except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 5 years prior to enrollment.
Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation.
Patients with psychiatric illness, social situation or geographical situation that would preclude informed consent or limit compliance with study requirements, as determined by the Investigator.

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

Italy9 sites

A.O. Ospedale Papa Giovanni XXIII - Oncologia
Bergamo
I.R.C.C.S. A.O.U San Martino - IST
Genova
A.O.U. Policlinico di Modena
Modena
Azienda Ospedaliera Universitaria Federico II
Naples
Ospedale S. Cuore Don Calabria
Negrar
Fondazione Policlinico Universitario A. Gemelli - Oncologia Medica
Roma
Fondazione Policlinico Universitario A. Gemelli - Senologia Oncologica
Roma
Istituto Nazionale Tumori "Regina Elena"
Roma
Policlinico Umberto I
Rome

Other trials in Italy

About this study

Official title: Liquid Biopsy: Intercepting Mutational Trajectories of HER2 Breast Cancer Inpatients Under T-DM1 Treatment

Read the detailed description

T-DM1 effects will be monitored by a combination of Next Generation Sequencing (NGS, tumor tissue) and Liquid Biopsy (LB, blood), as described below, to capture molecular events (gene aberrations, mainly mutations) associated with (or causative of) relapse as well as primary/adaptive resistance to HER2 blockade.

This study will prospectively monitor these events throughout the clinical history of the patients (archival tissues, blood collection, aimed biopsies). No investigational drugs will be administered.

This protocol is classified as "interventional" for two reasons:

dedicated, additional blood drawings (liquid biopsies)are collected in addition to the routine bloodtests being requested as per standard clinical practice;
the study involves occasional fine-needle biopsy on accessible (e.g. cutaneous) metastatic foci in selected patients to confirm their HER2 status, as per good medical practice.

These will represent an additional opportunity of targeted NGS.

Both blood (a) and tissues (b) will be obtained during T-DM1 treatment of enrolled patients at the participating Sites at the study specific timelines.

Conditions: Metastatic Breast Cancer
Being tested: Both blood and tissues collection for patients with metastatic breast cancer HER2+ pretreated with no more than one line of anti-HER2 therapy for advanced breast cancer.
Keywords: LiqERBcept, Trastuzumab emtansine, Liquid Biopsy
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Both blood and tissues collection for patients with metastatic breast cancer HER2+ pretreated with no more than one line of anti-HER2 therapy for advanced breast cancer.Other
Both blood and tissues will be obtained duringT-DM1 treatment of enrolled patients at the participating Sites at the study specific timelines.

Study groups in NCT05735392
Study group	Role	What they receive
Trastuzumab emtansine as per SmPC for liquid biopsy and tissue collection	Other	Patients will receive trastuzumab emtansine (T-DM1) at 3.6 mg/kg intravenously every 21 days, as perSummary of Product Characteristics (SmPC). Peripheral blood samples will be taken by venipuncture prior to initiation of study therapy (T0), and at designated time-points after the first (T1) the second (T2), the third(T3)and after the sixth(T6), the ninth(T9), until the 12thcycle of T-DM1(see Fig.1) on-treatment and finally at progression. Receives: Other: Both blood and tissues collection for patients with metastatic breast cancer HER2+ pretreated with no more than one line of anti-HER2 therapy for advanced breast cancer.

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of index mutations
1. Number of index mutations and resistance-associated mutations in the bloodstream. Index mutations are defined as the number of mutation detected in tissue biopsies from either or both the primary lesions and the most recent recurrence, whenever available. Resistance mutations known to arise during non-T-DM1 HER2-blockade include mutations of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1), AKT1 (AKT1 AKT serine/threonine kinase 1), and EGF1R (Epidermal Growth Factor Receptor 1).These may be a special case of index mutations. Other known genomic aberrations occurring under HER2 blockade and potentially testable in bloodier PTEN (Phosphatase and tensin homolog) loss and overexpression of p95HER2 (p95HER2/611 carboxy terminal fragment), MUC4 (Mucin 4, Cell Surface Associated), and PDK1 (3-Phosphoinositide-dependent kinase 1)
Measured: About 4 years
Rate of response/anticipation of relapse
1. Changes form baseline in thr response rate. First detection of index mutations in blood will be compared with first imaging and medical evidence of relapse (response rate) to determine whether and how the LiqERBcept protocol can lead to earlier detection and improvement in medical care.
Measured: About 4 years
Number of de novo mutations
1. Number of de novo mutations arising during T-DM1 treatment. Few mutations and gene aberrations (see above) are known to associate with primary and acquired resistance to Trastuzumab (TTZ) and Pertuzumab (PTZ), and none is specifically associated with T-DM1 escape, to our knowledge. Possibly, this is due to the rather recent introduction of this antibody-drug conjugate in human therapy.
Measured: About 4 years

Secondary outcomes (1)

Number of actionable mutations
Number of actionable mutations occur during treatment with T-DM1 .
Measured: About 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Nov 201812 Jan 2022

First posted21 Feb 2023
Study start7 Nov 2018
Primary completion12 Jan 2022
Study completion12 Jan 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for 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 N/A
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05735392
Sponsor's protocol ID: GIM21 - LiqERBcept
Acronym: GIM21
Status last verified: Jan 2023
First submitted: 31 Jan 2023
Last updated: 21 Feb 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Fabi A, Giordani E, Ricciardi E, Arpino G, Allegretti M, Ferretti G, Omarini C, Zambelli A, Mandoj C, Botticelli A, Bria E, Gori S, Carbognin L, Paris I, Scambia G, Cognetti F, Giannarelli D, Giacomini P. Circulating tumor DNA and Response Evaluation Criteria In Solid Tumors: ctDNA-RECIST proof-of-concept in HER2-positive metastatic breast cancer. J Exp Clin Cancer Res. 2026 Jan 20;45(1):67. doi: 10.1186/s13046-025-03605-2.
PubMed 41559726
Giordani E, Allegretti M, Sinibaldi A, Michelotti F, Ferretti G, Ricciardi E, Ziccheddu G, Valenti F, Di Martino S, Ercolani C, Giannarelli D, Arpino G, Gori S, Omarini C, Zambelli A, Bria E, Paris I, Buglioni S, Giacomini P, Fabi A. Monitoring changing patterns in HER2 addiction by liquid biopsy in advanced breast cancer patients. J Exp Clin Cancer Res. 2024 Jun 29;43(1):182. doi: 10.1186/s13046-024-03105-9.
PubMed 38951853

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Metastatic Breast Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Liquid Biopsy: Intercepting Mutational Trajectories of HER2 Breast Cancer Inpatients Under T-DM1 Treatment
ClinicalTrials.gov ID: NCT05735392
Acronym / sponsor ID: GIM21 / GIM21 - LiqERBcept
Conditions: Metastatic Breast Cancer
Keywords: LiqERBcept, Trastuzumab emtansine, Liquid Biopsy
Study type: Interventional
Recruitment status: Completed
Enrolment: 48 participants (actual)
Lead sponsor: Consorzio OncotechUniversity, hospital or other
Study start: 7 Nov 2018 (actual)
Primary completion: 12 Jan 2022 (actual)
Study completion: 12 Jan 2022 (actual)
First posted: 21 Feb 2023 (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.

Detailed description

This study will prospectively monitor these events throughout the clinical history of the patients (archival tissues, blood collection, aimed biopsies). No investigational drugs will be administered.

This protocol is classified as "interventional" for two reasons:

dedicated, additional blood drawings (liquid biopsies)are collected in addition to the routine bloodtests being requested as per standard clinical practice;
the study involves occasional fine-needle biopsy on accessible (e.g. cutaneous) metastatic foci in selected patients to confirm their HER2 status, as per good medical practice.

These will represent an additional opportunity of targeted NGS.

Both blood (a) and tissues (b) will be obtained during T-DM1 treatment of enrolled patients at the participating Sites at the study specific timelines.

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Trastuzumab emtansine as per SmPC for liquid biopsy and tissue collection	Other	Other: Both blood and tissues collection for patients with metastatic breast cancer HER2+ pretreated with no more than one line of anti-HER2 therapy for advanced breast cancer.Patients will receive trastuzumab emtansine (T-DM1) at 3.6 mg/kg intravenously every 21 days, as perSummary of Product Characteristics (SmPC). Peripheral blood samples will be taken by venipuncture prior to initiation of study therapy (T0), and at designated time-points after the first (T1) the second (T2), the third(T3)and after the sixth(T6), the ninth(T9), until the 12thcycle of T-DM1(see Fig.1) on-treatment and finally at progression.

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)

Male and female patients with a documented diagnosis of metastatic HER2-positive breast cancer (BC) as defined by an immunohistochemistry (IHC) score of 3+, alternatively score 2+ and HER2 amplification ratio ≥ 2.0
All patients eligible to treatment with T-DM1, according to SmPC previously treated with a taxane and trastuzumab. Patients who previously underwent first-line treatment with an association of TTZ with PTZ are also eligible. No more than one line of anti-HER2 treatment for advanced disease are allowed.
Available tissue from the primary tumor. If possible, newly obtained core or excisional biopsy on metastatic site at baseline (this biopsy won't impact on timing for patient enrollment and not leading to patient exclusion). High quality genomic DNA from the above for NGS mutational analysis.
Patients with both measurable and non-measurable disease (according to modified RECIST 1.1 criteria) are eligible.
18 years of age on day of signing informed consent.

Key exclusion criteria (8 listed)

Prior treatment with T-DM1.
Symptomatic central nervous system (CNS) metastases, or treatment for these metastases within the 2 months preceding enrollment.
Current participation in study therapy, or previous participation in a study involving the administration of an investigational agent within 4 weeks of administration of the first dose of treatment.
History of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment; a history of myocardial infarction or unstable angina within 6 months before.
Female patients who are pregnant or lactating, who plan to get pregnant, or who have a positive serum pregnancy test prior to first dose of study treatment.

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
Both blood and tissues collection for patients with metastatic breast cancer HER2+ pretreated with no more than one line of anti-HER2 therapy for advanced breast cancer.Both blood and tissues will be obtained duringT-DM1 treatment of enrolled patients at the participating Sites at the study specific timelines.	Other	Trastuzumab emtansine as per SmPC for liquid biopsy and tissue collection

Primary outcome

Number of index mutations
Time frame: About 4 years
1. Number of index mutations and resistance-associated mutations in the bloodstream. Index mutations are defined as the number of mutation detected in tissue biopsies from either or both the primary lesions and the most recent recurrence, whenever available. Resistance mutations known to arise during non-T-DM1 HER2-blockade include mutations of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1), AKT1 (AKT1 AKT serine/threonine kinase 1), and EGF1R (Epidermal Growth Factor Receptor 1).These may be a special case of index mutations. Other known genomic aberrations occurring under HER2 blockade and potentially testable in bloodier PTEN (Phosphatase and tensin homolog) loss and overexpression of p95HER2 (p95HER2/611 carboxy terminal fragment), MUC4 (Mucin 4, Cell Surface Associated), and PDK1 (3-Phosphoinositide-dependent kinase 1)
Rate of response/anticipation of relapse
Time frame: About 4 years
2. Changes form baseline in thr response rate. First detection of index mutations in blood will be compared with first imaging and medical evidence of relapse (response rate) to determine whether and how the LiqERBcept protocol can lead to earlier detection and improvement in medical care.
Number of de novo mutations
Time frame: About 4 years
3. Number of de novo mutations arising during T-DM1 treatment. Few mutations and gene aberrations (see above) are known to associate with primary and acquired resistance to Trastuzumab (TTZ) and Pertuzumab (PTZ), and none is specifically associated with T-DM1 escape, to our knowledge. Possibly, this is due to the rather recent introduction of this antibody-drug conjugate in human therapy.

1 secondary outcome

Number of actionable mutations
Time frame: About 4 years

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
Derived from this study: PubMed 41559726Fabi A, Giordani E, Ricciardi E, Arpino G, Allegretti M, Ferretti G, Omarini C, Zambelli A, Mandoj C, Botticelli A, Bria E, Gori S, Carbognin L, Paris I, Scambia G, Cognetti F, Giannarelli D, Giacomini P. Circulating tumor DNA and Response Evaluation Criteria In Solid Tumors: ctDNA-RECIST proof-of-concept in HER2-positive metastatic breast cancer. J Exp Clin Cancer Res. 2026 Jan 20;45(1):67. doi: 10.1186/s13046-025-03605-2.
Derived from this study: PubMed 38951853Giordani E, Allegretti M, Sinibaldi A, Michelotti F, Ferretti G, Ricciardi E, Ziccheddu G, Valenti F, Di Martino S, Ercolani C, Giannarelli D, Arpino G, Gori S, Omarini C, Zambelli A, Bria E, Paris I, Buglioni S, Giacomini P, Fabi A. Monitoring changing patterns in HER2 addiction by liquid biopsy in advanced breast cancer patients. J Exp Clin Cancer Res. 2024 Jun 29;43(1):182. doi: 10.1186/s13046-024-03105-9.

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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.

Alessandra Fabi, MD principal investigator

Clinical issues - Fondazione Policlinico Gemelli

Patrizio Giacomini principal investigator

Central laboratory assesment and liquid biopsy - Oncogenomics and Epigenetics - Istituto Nazionale Tumori "Regina Elena"

Francesco Cognetti study chair

Chairman - Istituto Nazionale Tumori "Regina Elena"

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 8 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: finished, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Italy. 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.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Number of index mutations (time frame: About 4 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05735392, which also lists 2 linked publications.

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 21 Feb 2023.