Impact of Pegfilgrastim on Trastuzumab Anti-tumor Effect and ADCC in Operable HER2+ Breast Cancer Breast Cancer (BREASTIMMU02)

November 21, 2025 updated by: Centre Leon Berard

A Multicenter, Randomized, Open-label, Phase II Trial Aiming to Evaluate the Impact of Pegfilgrastim on Trastuzumab Anti-tumor Effect and ADCC in Operable HER2 Positive Breast Cancer Patients

First preclinical data suggest that pegfilgrastim could constitute a potent adjuvant for immunotherapy with mAb possessing ADCC/ADCP properties as trastuzumab. Combined treatment of pegfilgrastim and trastuzumab should translate into an increased rate of pathological clinical response. Therefore the investigators' proposal is to evaluate the clinical and biological impact of pegfilgrastim in combination with trastuzumab + paclitaxel in HER2-positive early stage breast cancer patients. Breastimmune02 is a multicenter, randomized, open-label, Phase II trial. Operable HER2+ breast cancer patients previously treated with 4 cycles of standard adriamycine/cyclophosphamide (AC) chemotherapy will be randomized (1:1) to receive in the neoadjuvant setting:Arm A: weekly paclitaxel + trastuzumab (every 3 weeks, Q3W) + pegfilgrastim (Q3W) versus Arm B: weekly paclitaxel + trastuzumab (Q3W).Stratification criteria will be: cN0 versus cN1.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The duration of the neoadjuvant treatment period is planned to be 12 weeks (4 cycles of 3 weeks), except in case of Inacceptable toxicity, or Patient decision, or Withdrawal of consent, or Clinical/radiological signs of disease progression.This neoadjuvant treatment period will be ended with a short term safety visit (STSVNeo) to be scheduled 28 days after the last dose of study treatments (considering the latest study treatments administered). Following the STSVNeo, patients will undergo surgery as per usual practice and pathological response will be centrally assessed by a referent pathologist blinded for the treatment arms.Following surgery, all patients will be treated in the adjuvant setting with trastuzumab administered every 3 weeks for up to 12 months in both arms with clinical assessments every 3 months (cf. Réseau régional de Cancérologie, http://espacecancer.sante-ra.fr/Pages/Accueil.aspx). In case of RH+ disease, endocrine therapy may be initiated as per standard treatment guidelines.This adjuvant treatment period is planned for a maximum of 12 months; except in case of Inacceptable toxicity, or Patient decision, or Withdrawal of consent, or Clinical/radiological signs of disease progression. All randomized and treated patients will be followed-up for relapse and survival for at least 15 months post-randomization (i.e. 1 year post-surgery).

A total of 90 patients will be randomized in the study. (45 per arm). All the data concerning the patients will be recorded in the electronic case report form (eCRF) throughout the study serious adverse event (SAE) reporting will be also paper-based by e-mail and/or Fax. The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local law requirements

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Avignon, France
        • Institut Sainte Catherine
      • Besançon, France, 25000
        • CHRU Besançon
      • Clermont-Ferrand, France, 63000
        • Centre de Lutte Contre le Cancer Jean PERRIN
      • Grenoble, France, 38000
        • Groupe hospitalier mutualiste de Grenoble
      • Lyon, France
        • Centre Leon Berard
      • Lyon, France
        • Hôpital Privé Jean Mermoz
      • Pringy, France
        • Centre Hospitalier Annecy Genevois
      • Saint-Etienne, France
        • Centre Hospitalier Universitaire de Saint Etienne
      • Sainte-Foy-lès-Lyon, France
        • Clinique Charcot

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female patients aged ≥ 18 years at time of inform consent signature.
  • Histologically proven HER2 positive breast cancer defined as 3+ staining intensity by immunohistochemistry (IHC) or a 2+ IHC staining intensity and HER2 gene amplification by FISH.Note: HER2 status will be determined as per institutional practice.
  • Operable breast tumor with tumor size and staging: > 20 mm, cN0 or cN1, M0 before any AC or FEC chemotherapy, and at least one measurable lesion ≥10 mm in longest diameter at inclusion according to RECIST 1.1.
  • No radiological sign of disease progression at time of randomisation.
  • Patient previously treated by 4 cycles of AC or 3 to 4 cycles of FEC without febrile neutropenia and without prior pegfilgrastim treatment.
  • Availability of a representative formalin-fixed paraffin-embedded (FFPE) tumor specimen from initial diagnosis (i.e. an archival paraffin block is preferred; or at least 20 unstained slides) with its histological report.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Adequate organ function as defined by the following lab tests (to be carried out within 7 days prior C1D1):Bone marrow (Absolute neutrophil count ≥ 1.5 x 109/L, Platelet count > 100 x 109/L, (without transfusion within 21 days prior to C1D1), Hemoglobin value ≥ 9 g/dL), Renal function (Calculated creatinine clearance by MDRD or CKD-EPI >50 mL/min/1.73m2 or serum creatinine < 1.5ULN), Liver function (Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3ULN, Total serum bilirubin ≤ 1.5 ULN (except for patients with Gilbert disease for whom a total serum bilirubin ≤3 ULN is acceptable), Coagulation (INR and aPTT≤ 1.5 ULN)
  • Adequate cardiac function with Mean resting corrected QT interval (QTc), calculated using Fridericia's formula, ≤470ms obtained from 3 electrocardiograms (ECGs) and Systolic blood pressure <160mmHg and Diastolic blood pressure <100mmHg (hypertension controlled by standard medical treatment is allowed)
  • Women of childbearing potential (entering the study after a confirmed menstrual period and who have a negative pregnancy test within 7 days before C1D1) must agree to use two methods of medically acceptable forms of contraception from the date of negative pregnancy test to 3 months after the last study drug intake
  • Patients should be able and willing to comply with study visits and procedures as per protocol
  • Patients should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed.
  • Patients must be covered by a medical insurance.

Exclusion Criteria:

  • Patients with inflammatory breast cancer.
  • Previous exposure to pegfilgrastim or trastuzumab. Note: the use of filgrastim (non pegylated form only) is authorized prior to the randomisation.
  • Patients requiring the concomitant use of any forbidden treatment including: Any other anti-cancer treatments not listed in the protocol, including chemotherapy, radiotherapy, immunotherapy, targeted therapy or biologic therapy for cancer treatment, Any investigational treatment.
  • Any contra-indication to trastuzumab, paclitaxel, and pegfilgrastim respective SPCs including:Hypersensitivity to trastuzumab, murine proteins, or to any of the excipients listed in trastuzumab SPC, Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy, Hypersensitivity to pegfilgrastim or filgrastim, or to any of the excipients listed in SPC, Hereditary problems of fructose intolerance, Hypersensitivity to paclitaxel or to any excipient, particularly macrogolglycerol ricinoleate, Patients with history of or active cardiac disease including myocardial infarction (MI), angina pectoris requiring medical treatment, congestive heart failure NYHA (New York Heart Association) Class ≥II, other cardiomyopathy, cardiac arrhythmia requiring medical treatment, clinically significant cardiac valvular disease, and hemodynamic effective pericardial effusion.
  • Active secondary malignancy unless this malignancy is not expected to interfere with the evaluation of study endpoints and is approved by the sponsor. Examples of the latter include basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix. Patients with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.
  • Pregnant or breast-feeding female patients.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Paclitaxel+Trastuzumab+Pegfilgrastim

NEOADJUVANT TREATMENT PERIOD (up to 12 weeks) :Paclitaxel (80 mg/m2, weekly (D1, D8, D15), IV) + Trastuzumab (a loading dose 8 mg/kg at C1D1 followed by 6 mg/kg Q3W, IV OR 600mg, Q3W SC) + Pegfilgrastim (6 mg, Q3W, subcutaneously, the day after the trastuzumab + paclitaxel infusion (i.e. Day 2 of each cycle)).

ADJUVANT TREATMENT PERIOD (up to 12 months) : Trastuzumab (a loading dose 8 mg/kg at C1D1 followed by 6 mg/kg Q3W, (IV) OR 600mg, Q3W SC)
Drug: Trastuzumab + Paclitaxel
During neoadjuvant period, weekly paclitaxel + trastuzumab (every 3 weeks, Q3W) During adjuvant period, weekly trastuzumab (every 3 weeks, Q3W)
Drug: Pegfilgrastim
During neoadjuvant period, weekly pegfilgrastim (every 3 weeks, Q3W)
Other Names:
  • Neulasta
Active Comparator: Paclitaxel+Trastuzumab

NEOADJUVANT TREATMENT PERIOD (up to 12 weeks) :Paclitaxel (80 mg/m2, weekly (D1, D8, D15), IV) + Trastuzumab (a loading dose 8 mg/kg at C1D1 followed by 6 mg/kg Q3W, IV OR 600mg, Q3W SC).

ADJUVANT TREATMENT PERIOD (up to 12 months) : Trastuzumab (a loading dose 8 mg/kg at C1D1 followed by 6 mg/kg Q3W, (IV) OR 600mg, Q3W SC)
Drug: Trastuzumab + Paclitaxel
During neoadjuvant period, weekly paclitaxel + trastuzumab (every 3 weeks, Q3W) During adjuvant period, weekly trastuzumab (every 3 weeks, Q3W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological complete response rate (pCR)
Time Frame: 16 weeks after start of treatment
Defined as ypT0 ypN0 or ypT0/is ypN0 after 12 weeks of treatment by trastuzumab + paclitaxel ± pegfilgrastim with ypT0/Tis ypN0 defined as absence of invasive cancer in the breast and axillary nodes in all surgically excised specimens.
16 weeks after start of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Free survival
Time Frame: At least 15 months following randomisation
From the date of randomisation until the date of event defined as the first documented relapse after surgery or death from any cause.
At least 15 months following randomisation
Time to relapse
Time Frame: At least 15 months following randomisation
From the time of treatment start until the first documented relapse
At least 15 months following randomisation
Overall survival
Time Frame: At least 15 months following randomisation
From the date of randomisation to the date of death from any cause
At least 15 months following randomisation
Adverse events reporting
Time Frame: At least 15 months following randomisation
Based mainly on the frequency of AE graded according to the common toxicity criteria grading system (CTCAE-V4.03).
At least 15 months following randomisation

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Trastuzumab ADCC activity
Time Frame: At Baseline, at Day 1 of Cycle 2 (each cycle is a 21-day cycle) and at surgery
Analysis of the levels of the ADCC tumor samples
At Baseline, at Day 1 of Cycle 2 (each cycle is a 21-day cycle) and at surgery
HER2 signaling
Time Frame: At Baseline, at Day 1 of Cycle 2 (each cycle is a 21-day cycle) and at surgery
Evaluation of the levels of phosphorylated components of PI3K/mTOR and Ras/Raf /MAPK signaling (IHC or IF)
At Baseline, at Day 1 of Cycle 2 (each cycle is a 21-day cycle) and at surgery
Immune effector cells activity
Time Frame: At Baseline, at Day 1 of Cycle 2 (each cycle is a 21-day cycle) and at surgery
Analysis of activity of immune effector cells (frequency, function, activation status and ADCC)
At Baseline, at Day 1 of Cycle 2 (each cycle is a 21-day cycle) and at surgery
TGFbeta levels
Time Frame: At Baseline
Levels of TGFβ (bioactive and non-bioactive) in serum, plasma and platelets
At Baseline
Residual disease of class
Time Frame: At surgery
Evaluation of RCB Class by local pathologist and blinded independent central review after 12 weeks of treatment
At surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Leon Berard

Collaborators

Amgen

Investigators

  • Principal Investigator: Olivier TREDAN, MD, Centre Leon Berard

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 6, 2018

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

September 1, 2027

Study Registration Dates

First Submitted

June 4, 2018

First Submitted That Met QC Criteria

June 18, 2018

First Posted (Actual)

June 27, 2018

Study Record Updates

Last Update Posted (Actual)

November 26, 2025

Last Update Submitted That Met QC Criteria

November 21, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ET17-057
  • 2017-002069-22 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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