HER2-positive Breast CancerBiOnHERNCT05912062
Early On-treatment Transcriptional Profiling as Predictor of Response in Early-stage HER2-positive Breast Cancer
An observational study of HER2-positive Breast Cancer and Neoplasms, run by Institut Català d'Oncologia at 1 site in Spain.
Trial summary
Non-randomized, open label, translational research study in women with early HER2-positive invasive breast carcinoma eligible for neoadjuvant treatment. The aim of BIONHER is to assess the impact of short-term neoadjuvant dual HER2-blockade on HER2-positive breast cancer transcriptomic profile and to evaluate whether… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-positive Breast Cancer, Neoplasms, Breast Cancer
- What is being tested?
- Trastuzumab (neoadjuvant), Pertuzumab (neoadjuvant) and Paclitaxel (neoadjuvant)
- How many people
- 80 participants
- Where
- 1 siteSpain
- Study dates
- 22 Mar 2021to 1 Dec 2024
- Phase
- Observational
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients enrolled in this study will be patients with early-stage HER2-positive breast cancer treated with neoadjuvant trastuzumab, pertuzumab (HP) and paclitaxel within standard clinical practice at the Catalan Institute of Oncology (ICO) Hospitalet.
Who may be able to join
- Written informed consent prior to beginning specific protocol procedures
- Untreated invasive breast carcinoma eligible for neoadjuvant treatment
- Histologically or cytologically confirmed human epidermal growth factor receptor 2 positive (HER2) Breast Cancer defined by ASCO/CAP guidelines based on the most recent analyzed biopsy or other pathology specimen; independently for estrogen receptor (ER) and progesterone receptor (PR)
- Female and male patients
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Show all 10Show fewer
- Adequate organ function defined as: Absolute neutrophil count (ANC) ≥1.5 × 109/L, Hemoglobin (Hgb) ≥10 g/dL, Platelets >100 000/mm3, Creatinine ≤1.6 mg/dL, ALT and AST ≤2.5 × ULN, Alkaline phosphatase ≤5 ULN, Total bilirubin ≤1.5 mg/dL
- Baseline LVEF ≥50% measured by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan
- Negative β-HCG pregnancy test (serum) for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after the menopause. All subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control from 2 weeks before administration of the first dose of investigational product until 28 days after last dose of investigational product
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Who cannot join
- Known metastatic disease
- Known or suspected hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances
- Concurrent congestive heart failure or LVEF <50%
- History of significant comorbidities that, in the judgment of the investigator, may interfere with the conduction of the study, the evaluation of response, or with informed consent
- Use of any investigational agent or participation in another therapeutic clinical trial concurrently or in the previous 30 days before the enrollment
- Patients who are pregnant or breast-feeding
Show all 9Show fewer
- Women of child-bearing potential who are unable or unwilling to use contraceptive measures
- Inability or unwillingness to abide by the study protocol or cooperate fully with the investigator
- Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy other than the trial therapies)
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Institut Català d'Oncologia l'Hospitalet
L'Hospitalet de Llobregat, Barcelona, 08908
Sonia Pernas, MD PhD, +34932607744, contactfortrials_lh@iconcologia.net
+34677382072, contactfortrials_lh@iconcologia.net
About this study
Official title: Early On-treatment Transcriptional Profiling as Predictor of Response in Early-stage HER2-positive Breast Cancer (BiOnHER)
Non-randomized, open label, translational research study in women with early HER2-positive invasive breast carcinoma eligible for neoadjuvant treatment.
The aim of BIONHER is to assess the impact of short-term neoadjuvant dual HER2-blockade on HER2-positive breast cancer transcriptomic profile and to evaluate whether early on treatment tumor biopsy can improve the accuracy of predicting response over the pre-treatment alone.
Read the detailed description
This is a prospective study of paired tumor samples from patients with newly diagnosed HER2-positive breast cancer eligible for neoadjuvant treatment to evaluate whether early on-treatment biomarkers can improve the accuracy of predicting response over pre-treatment samples alone.
Sequential tumor biopsies will be obtained at two time points: before initiation of neoadjuvant dual HER2-blockade (pre-treatment, day 1) and 1 week later (day 8), before introduction of paclitaxel to the neoadjuvant treatment.
Following the completion of neoadjuvant paclitaxel, trastuzumab and pertuzumab (THP) for 16 weeks, patients will proceed to surgery. After surgery, adjuvant treatment (including need for Anthracyclines) will be followed as per clinical practice.
The study will comprise two phases: a discovery phase (n=60) where sequential paired tumor biopsies will be used for RNA-Seq analysis and assessment of tumor infiltrating lymphocytes (TILs) and CelTIL score. Radiomic characteristics of MRI, HER2Dx® and spatial transcriptomics (using GeoMx®) will be also evaluated.
This phase will be followed by a validation phase (n=20) in which prediction accuracy observed in the discovery phase will be validated by Nanostring gene expression analysis using a new cohort of patients with HER2-positive breast cancer eligible for neoadjuvant therapy.
- Conditions
- HER2-positive Breast Cancer, Neoplasms, Breast Cancer
- Being tested
- Trastuzumab (neoadjuvant), Pertuzumab (neoadjuvant), Paclitaxel (neoadjuvant)
- Keywords
- Neoadjuvant HER2-positive Breast Cancer, Human Epidermal Growth Factor Receptor 2, Biomarker, Radiomic, Transcriptomics, Spatial transcriptomics, HER2Dx
- Medical subject headings
- Neoplasms, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab (neoadjuvant)Drug
Trastuzumab loading dose at 8mg/kg at day 1 followed by Trastuzumab at 6mg/kg in a 21-day cycle for six cycles
Pertuzumab (neoadjuvant)Drug
Pertuzumab loading dose at 840mg at day 1 followed by Pertuzumab at 420mg in a 21-day cycle for six cycles
Paclitaxel (neoadjuvant)Drug
Paclitaxel starting at day 8 at 80mg/m2, days 1, 8, and 15 of a 21-day cycle for up to fifteen weeks
| Study group | Role | What they receive |
|---|---|---|
| early-stage HER2-positive breast cancer neoadjuvant treatment | For a total of 16 weeks, patients will be given dual antiHER2 blockade consisting of Cycle 1 Day 1 Pertuzumab 840mg + Trastuzumab 8mg/kg loading dose, followed by Paclitaxel starting at Cycle 1 day 8 and 15 at 80mg/m2. Followed by Pertuzumab 420mg + Trastuzumab 6mg/kg every three weeks and Paclitaxel days 1, 8, and 15 of a 21-day cycle for up to fifteen weeks.
Adjuvant treatment (including the need of Anthracyclines) will be administered according clinical practice. Receives: Drug: Trastuzumab (neoadjuvant); Drug: Pertuzumab (neoadjuvant); Drug: Paclitaxel (neoadjuvant) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in gene expression (by RNA-seq technology) induced by a single dose of dual HER2-blockade with pertuzumab and trastuzumab.
Measured: Between day 1 and day 8
Secondary outcomes (5)
Gene expression patterns (by RNA-seq technology) induced by a single dose of dual HER2-blockade with pertuzumab and trastuzumab to better predict pathological complete response (pCR) in HER2-positive breast cancer
Measured: Between day 1 and day 8
Characterize the immune component of the tumor microenvironment (TME) using Spatial transcriptomics.
Measured: Between day 1 and day 8
Changes in the immune component of TME induced early by treatment after the first dose of dual anti-HER2 blockade that are associated with pCR.
Measured: Between day 1 and day 8
Clinical and radiomic characteristics of MRI together with machine learning for a better prediction of which patients will achieve a pCR and which will not
Measured: Between MRI at diagnosis and pre-surgery
Machine learning for a construction and validation of (by Nanostring technology) an early predictor of response to the neoadjuvant treatment to distinguish between responders and nonresponders.
Measured: Between day 1 and day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2023
- Study start22 Mar 2021
- Primary completion1 Jun 2024 (estimated)
- Study completion1 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HER2-positive 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Català d'Oncologia
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto de Salud Carlos III, Fundación Sociedad Española de Oncologia Médica, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Reveal Genomics (Registered trademark)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05912062
- Sponsor's protocol ID
- PI20/00544
- Acronym
- BiOnHER
- Status last verified
- Sep 2023
- First submitted
- 12 Jun 2023
- Last updated
- 29 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pernas S, Guerriero JL, Naumenko S, Goel S, Regan MM, Hu J, Harrison BT, Lynce F, Lin NU, Partridge A, Morikawa A, Hutchinson J, Mittendorf EA, Sokolov A, Overmoyer B. Early on-treatment transcriptional profiling as a tool for improving pathological response prediction in HER2-positive inflammatory breast cancer. Ther Adv Med Oncol. 2022 Jul 30;14:17588359221113269. doi: 10.1177/17588359221113269. eCollection 2022.
PubMed 35923923
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early On-treatment Transcriptional Profiling as Predictor of Response in Early-stage HER2-positive Breast Cancer (BiOnHER)
- ClinicalTrials.gov ID
- NCT05912062
- Acronym / sponsor ID
- BiOnHER / PI20/00544
- Conditions
- HER2-positive Breast Cancer, Neoplasms, Breast Cancer
- Keywords
- Neoadjuvant HER2-positive Breast Cancer, Human Epidermal Growth Factor Receptor 2, Biomarker, Radiomic, Transcriptomics, Spatial transcriptomics, HER2Dx
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Institut Català d'OncologiaUniversity, hospital or other
- Collaborators
- Instituto de Salud Carlos III, Fundación Sociedad Española de Oncologia Médica, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Reveal Genomics (Registered trademark)
- Study start
- 22 Mar 2021 (actual)
- Primary completion
- 1 Jun 2024 (estimated)
- Study completion
- 1 Dec 2024 (estimated)
- First posted
- 22 Jun 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.
Non-randomized, open label, translational research study in women with early HER2-positive invasive breast carcinoma eligible for neoadjuvant treatment.
The aim of BIONHER is to assess the impact of short-term neoadjuvant dual HER2-blockade on HER2-positive breast cancer transcriptomic profile and to evaluate whether early on treatment tumor biopsy can improve the accuracy of predicting response over the pre-treatment alone.
Detailed description
This is a prospective study of paired tumor samples from patients with newly diagnosed HER2-positive breast cancer eligible for neoadjuvant treatment to evaluate whether early on-treatment biomarkers can improve the accuracy of predicting response over pre-treatment samples alone.
Sequential tumor biopsies will be obtained at two time points: before initiation of neoadjuvant dual HER2-blockade (pre-treatment, day 1) and 1 week later (day 8), before introduction of paclitaxel to the neoadjuvant treatment.
Following the completion of neoadjuvant paclitaxel, trastuzumab and pertuzumab (THP) for 16 weeks, patients will proceed to surgery. After surgery, adjuvant treatment (including need for Anthracyclines) will be followed as per clinical practice.
The study will comprise two phases: a discovery phase (n=60) where sequential paired tumor biopsies will be used for RNA-Seq analysis and assessment of tumor infiltrating lymphocytes (TILs) and CelTIL score. Radiomic characteristics of MRI, HER2Dx® and spatial transcriptomics (using GeoMx®) will be also evaluated.
This phase will be followed by a validation phase (n=20) in which prediction accuracy observed in the discovery phase will be validated by Nanostring gene expression analysis using a new cohort of patients with HER2-positive breast cancer eligible for neoadjuvant therapy.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| early-stage HER2-positive breast cancer neoadjuvant treatment | – | Drug: Trastuzumab (neoadjuvant), Drug: Pertuzumab (neoadjuvant), Drug: Paclitaxel (neoadjuvant)For a total of 16 weeks, patients will be given dual antiHER2 blockade consisting of Cycle 1 Day 1 Pertuzumab 840mg + Trastuzumab 8mg/kg loading dose, followed by Paclitaxel starting at Cycle 1 day 8 and 15 at 80mg/m2. Followed by Pertuzumab 420mg + Trastuzumab 6mg/kg every three weeks and Paclitaxel days 1, 8, and 15 of a 21-day cycle for up to fifteen weeks. Adjuvant treatment (including the need of Anthracyclines) will be administered according clinical practice. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients enrolled in this study will be patients with early-stage HER2-positive breast cancer treated with neoadjuvant trastuzumab, pertuzumab (HP) and paclitaxel within standard clinical practice at the Catalan Institute of Oncology (ICO) Hospitalet.
Key inclusion criteria (10 listed)
- Written informed consent prior to beginning specific protocol procedures
- Untreated invasive breast carcinoma eligible for neoadjuvant treatment
- Histologically or cytologically confirmed human epidermal growth factor receptor 2 positive (HER2) Breast Cancer defined by ASCO/CAP guidelines based on the most recent analyzed biopsy or other pathology specimen; independently for estrogen receptor (ER) and progesterone receptor (PR)
- Female and male patients
- Age ≥18 years
Key exclusion criteria (9 listed)
- Known metastatic disease
- Known or suspected hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances
- Concurrent congestive heart failure or LVEF <50%
- History of significant comorbidities that, in the judgment of the investigator, may interfere with the conduction of the study, the evaluation of response, or with informed consent
- Use of any investigational agent or participation in another therapeutic clinical trial concurrently or in the previous 30 days before the enrollment
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 |
|---|---|---|
| Trastuzumab (neoadjuvant)Trastuzumab loading dose at 8mg/kg at day 1 followed by Trastuzumab at 6mg/kg in a 21-day cycle for six cycles | Drug | early-stage HER2-positive breast cancer neoadjuvant treatment |
| Pertuzumab (neoadjuvant)Pertuzumab loading dose at 840mg at day 1 followed by Pertuzumab at 420mg in a 21-day cycle for six cycles | Drug | early-stage HER2-positive breast cancer neoadjuvant treatment |
| Paclitaxel (neoadjuvant)Paclitaxel starting at day 8 at 80mg/m2, days 1, 8, and 15 of a 21-day cycle for up to fifteen weeks | Drug | early-stage HER2-positive breast cancer neoadjuvant treatment |
Primary outcome
Changes in gene expression (by RNA-seq technology) induced by a single dose of dual HER2-blockade with pertuzumab and trastuzumab.
Time frame: Between day 1 and day 8
5 secondary outcomes
Gene expression patterns (by RNA-seq technology) induced by a single dose of dual HER2-blockade with pertuzumab and trastuzumab to better predict pathological complete response (pCR) in HER2-positive breast cancer
Time frame: Between day 1 and day 8
Characterize the immune component of the tumor microenvironment (TME) using Spatial transcriptomics.
Time frame: Between day 1 and day 8
Changes in the immune component of TME induced early by treatment after the first dose of dual anti-HER2 blockade that are associated with pCR.
Time frame: Between day 1 and day 8
Clinical and radiomic characteristics of MRI together with machine learning for a better prediction of which patients will achieve a pCR and which will not
Time frame: Between MRI at diagnosis and pre-surgery
Machine learning for a construction and validation of (by Nanostring technology) an early predictor of response to the neoadjuvant treatment to distinguish between responders and nonresponders.
Time frame: Between day 1 and day 8
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2023.
- Background: PubMed 35923923Pernas S, Guerriero JL, Naumenko S, Goel S, Regan MM, Hu J, Harrison BT, Lynce F, Lin NU, Partridge A, Morikawa A, Hutchinson J, Mittendorf EA, Sokolov A, Overmoyer B. Early on-treatment transcriptional profiling as a tool for improving pathological response prediction in HER2-positive inflammatory breast cancer. Ther Adv Med Oncol. 2022 Jul 30;14:17588359221113269. doi: 10.1177/17588359221113269. eCollection 2022.
- Individual participant dataSharing planned: No
Related trials for HER2-positive Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Recruiting
Short-Term Reduced Dietary Protein in ER+/HER2- Breast Cancer Patients During Neoadjuvant Chemotherapy
Breast Cancer, Hormone Receptor Positive / HER2-negative Breast Cancer
Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
RecruitingObservational study
Patient Relevant Outcomes Improvement Program in High Risk Hormone Receptor Positive (HR+) Breast Cancer
HR+/HER2- Early Breast Cancer
RecruitingPhase 3
Adding an Immunotherapy Drug, MEDI4736 (Durvalumab), to the Usual Chemotherapy Treatment (Paclitaxel, Cyclophosphamide, and Doxorubicin) for Stage II-III Breast Cancer
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HER2-positive Breast Cancer and Neoplasms, run by Institut Català d'Oncologia at 1 site in Spain.
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 10 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 29 Sep 2023. 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 Spain. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sonia Pernas, MD PhD (+34932607744, contactfortrials_lh@iconcologia.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in gene expression (by RNA-seq technology) induced by a single dose of dual HER2-blockade with pertuzumab and trastuzumab. (time frame: Between day 1 and day 8). 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 NCT05912062, which also lists 1 linked publication.
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 29 Sep 2023.