Omission of Surgery in Clinically Low-risk HER2positive Breast Cancer With High HER2 Addiction and a Complete Response Following Standard Anti-HER2-based Neoadjuvant Therapy

NCT04578106 | Terminated Phase 2 Results

• 1 other identifier: HCB-ONC001 (ML41519)
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single arm, open-label, unicenter, exploratory study in women with primary operable HER2-positive, HER2-enriched/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression), to evaluate the omission of surgery and sentinel lymph node dissection in patients with HER2-E and ERBB2 high breast cancer who achieving a complete response following standard anti-HER2-based neoadjuvant therapy with paclitaxel/trastuzumab/pertuzumab. The primary trial objective is to estimate the loco-regional invasive disease-free survival at 3-year of patients who achieve a complete response based on imaging (i.e. Magnetic resonance imaging) and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery.

Conditions

HER2-positive Breast Cancer; Stage I Breast Cancer

Keywords

Breast Cancer; Her2-positive; Pertuzumab; Trastuzumab; Omission surgery

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival at 3years

  To estimate the loco-regional invasive disease-free survival (LR-IDFS) at 3-year of patients who achieve a complete response based on imaging and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery.

  3 years

Secondary Outcomes (2)

• pCR Rate

  pCR assessment was done following surgery after neoadjuvant therapy with paclitaxel and trastuzumzb/pertuzumab prior to adjuvant therapy

• Patient Reported Outcomes (Global Health Status)

  The questionnaire was filled by the patients at screening and post adjuvant therapy.

Study Arms (2)

Omission of surgery

EXPERIMENTAL

Neoadjuvant period: paclitaxel IV 80mg/m2 every week for 12 weeks with trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination (FDC) (a loading dose of 1200 mg pertuzumab and 600 mg trastuzumab followed by a maintenance dose of 600 mg pertuzumab and 600 mg trastuzumab once every 3 weeks) for 5 cycles. Adjuvant period: If no invasive tumor cells and no in situ disease are identified in the stereotactic-guided VAB,patients will be eligible to omit loco-regional surgery. Whole breast radiotherapy without nodal radiotherapy will then be performed. Trastuzumab and pertuzumab FDC will be continued to complete 1 year of treatment and adjuvant endocrine therapy will be indicated according to hormonal receptor status by IHC.

Biological: Trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination

Surgery

NO INTERVENTION

Neoadjuvant period: paclitaxel IV 80mg/m2 every week for 12 weeks with trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination (FDC) (a loading dose of 1200 mg pertuzumab and 600 mg trastuzumab followed by a maintenance dose of 600 mg pertuzumab and 600 mg trastuzumab once every 3 weeks) for 5 cycles. Surgery: If invasive tumor cells and/or in situ disease are identified, patients will undergo surgery. Adjuvant period: All patients will continue with Trastuzumab-emtansine (T-DM1) completing 1 year of treatment (14 cycles) and adjuvant endocrine therapy will be indicated according to hormonal receptor status by IHC.

Interventions

Trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination BIOLOGICAL

After 13 weeks of neoadjuvant treatment, a breast MRI will be performed. If a complete response is observed on breast MRI, patients will undergo a stereotactic-guided VAB of the marker area to obtain 12 cylinders of breast parenchyma, which is equivalent to 2 grams of tissue. If no invasive tumor cells and no in situ disease are identified in the stereotactic-guided VAB, patients will be eligible to omit loco-regional surgery.

Also known as: Omission of surgery

Omission of surgery

Eligibility Criteria

• Age: 40 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female participants who are at least 40 years of age on the day of signing the informed consent form with histologically confirmed diagnosis of breast cancer.
• A participant is eligible to participate if she is not pregnant, not breastfeeding.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Histologically confirmed invasive adenocarcinoma of the breast, with all of the following characteristics:
• HER2-positive status by local determination according to 2018 ASCO/CAP guidelines.
• PAM50 HER2-enriched subtype and ERBB2-high as predefined cutoff as per central determination.
• Unifocal invasive carcinoma: only 1 invasive focus can be observed (the tumor focus containing or not containing an in situ component)
• Tumor largest diameter ≤4 cm as defined by breast MRI.
• No nodal involvement (i.e. cN0). Any suspicious axillary node by ultrasound must be biopsied. If the biopsy or the FNA is negative of tumor cells, patient is eligible.
• No evidence of distant metastasis (M0) by routine clinical assessment.
• Patient must have known ER and PR status locally determined prior to study entry.
• Eligible for taxane therapy.
• Willingness of the patient to omit surgery if all criteria are met following neoadjuvant therapy.
• Estimated life expectancy of at least 5 years irrespective of the diagnosis of breast cancer.
• Breast cancer eligible for primary surgery

You may not qualify if:

• Has received prior anti-cancer therapy, including investigational agents, or treatment for primary invasive breast cancer.
• Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, TDM1 or paclitaxel.
• Clinical stage II, III or IV.
• History of radiotherapy in the ipsilateral breast or axilla.
• History of surgery of the ipsilateral axilla.
• Bilateral invasive breast cancer.
• Infiltrating lobular carcinoma.
• Multicentric or multifocal breast cancer, defined as the presence of two or more foci of cancer in the same or different quadrants of the same breast.
• Patients who have undergone sentinel lymph node biopsy prior to study treatment.
• Patient has active cardiac disease or a history of cardiac dysfunction
• Has an active infection requiring systemic therapy.
• \. Patients with a history of previous breast cancer are excluded.

Sponsors & Collaborators

• Fundacio Clinic Barcelona: lead
• SOLTI Breast Cancer Research Group: collaborator
• Roche Pharma AG: collaborator

Study Sites (1)

Hospital Clinic de Barcelona

Barcelona, Barcelona, 08036, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; 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

Results Point of Contact

• Title: Dr. Tomas Pascual
• Organization: Hospital Clínic de Barcelona

topascual@clinic.cat

932275400

Study Officials

• Aleix Prat, MD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

• Tomas Pascual, MD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 8, 2020
• Study Start: September 23, 2020
• Primary Completion: July 16, 2024
• Study Completion: July 16, 2024
• Last Updated: January 6, 2026
• Results First Posted: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)