Early On-treatment Transcriptional Profiling as Predictor of Response in Early-stage HER2-positive Breast Cancer

NCT05912062 | Unknown

• 1 other identifier: PI20/00544
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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 early on treatment tumor biopsy can improve the accuracy of predicting response over the pre-treatment alone.

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

Outcome Measures

Primary Outcomes (1)

• Changes in gene expression (by RNA-seq technology) induced by a single dose of dual HER2-blockade with pertuzumab and trastuzumab.

  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

  Between day 1 and day 8

• Characterize the immune component of the tumor microenvironment (TME) using Spatial transcriptomics.

  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.

  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

  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.

  Between day 1 and day 8

Study Arms (1)

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.

Drug: Trastuzumab (neoadjuvant); Drug: Pertuzumab (neoadjuvant); Drug: Paclitaxel (neoadjuvant)

Interventions

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

early-stage HER2-positive breast cancer neoadjuvant treatment

Pertuzumab (neoadjuvant) DRUG

Pertuzumab loading dose at 840mg at day 1 followed by Pertuzumab at 420mg in a 21-day cycle for six cycles

early-stage HER2-positive breast cancer neoadjuvant treatment

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

early-stage HER2-positive breast cancer neoadjuvant treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Institut Català d'Oncologia: lead
• Instituto de Salud Carlos III: collaborator
• Fundación Sociedad Española de Oncologia Médica: collaborator
• Institut d'Investigacions Biomèdiques August Pi i Sunyer: collaborator
• Reveal Genomics (Registered trademark): collaborator

Study Sites (1)

Institut Català d'Oncologia l'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

Related Publications (1)

• 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.

  PMID: 35923923 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Breast tumor tissue

MeSH Terms

Conditions

Neoplasms; Breast Neoplasms

Interventions

Trastuzumab; Neoadjuvant Therapy; pertuzumab; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Combined Modality Therapy; Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Central Study Contacts

Sonia Pernas, MD PhD

CONTACT

+34932607744; contactfortrials_lh@iconcologia.net

Bartomeu Fullana, MD

CONTACT

+34932607744; contactfortrials_lh@iconcologia.net

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2023
• First Posted: June 22, 2023
• Study Start: March 22, 2021
• Primary Completion: June 1, 2024
• Study Completion: December 1, 2024
• Last Updated: September 29, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)