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

NCT03571633 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: ET17-0572017-002069-22
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

HER2-positive Breast Cancer; Operable Breast Cancer

Keywords

Pegfilgrastim; Trastuzumab/Paclitaxel; Antibody-dependent cell-mediated cytotoxicity

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate (pCR)

  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 Outcomes (4)

• Disease Free survival

  At least 15 months following randomisation

• Time to relapse

  At least 15 months following randomisation

• Overall survival

  At least 15 months following randomisation

• Adverse events reporting

  At least 15 months following randomisation

Other Outcomes (5)

• Trastuzumab ADCC activity

  At Baseline, at Day 1 of Cycle 2 (each cycle is a 21-day cycle) and at surgery

• HER2 signaling

  At Baseline, at Day 1 of Cycle 2 (each cycle is a 21-day cycle) and at surgery

• Immune effector cells activity

  At Baseline, at Day 1 of Cycle 2 (each cycle is a 21-day cycle) and at surgery

Study Arms (2)

Paclitaxel+Trastuzumab+Pegfilgrastim

EXPERIMENTAL

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; Drug: Pegfilgrastim

Paclitaxel+Trastuzumab

ACTIVE COMPARATOR

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

Interventions

Trastuzumab + Paclitaxel DRUG

During neoadjuvant period, weekly paclitaxel + trastuzumab (every 3 weeks, Q3W) During adjuvant period, weekly trastuzumab (every 3 weeks, Q3W)

Paclitaxel+Trastuzumab; Paclitaxel+Trastuzumab+Pegfilgrastim

Pegfilgrastim DRUG

During neoadjuvant period, weekly pegfilgrastim (every 3 weeks, Q3W)

Also known as: Neulasta

Paclitaxel+Trastuzumab+Pegfilgrastim

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Leon Berard: lead
• Amgen: collaborator

Study Sites (9)

Institut Sainte Catherine

Avignon, France

Location

CHRU Besançon

Besançon, 25000, France

Location

Centre de Lutte contre le Cancer Jean Perrin

Clermont-Ferrand, 63000, France

Location

Groupe Hospitalier Mutualiste de Grenoble

Grenoble, 38000, France

Location

Centre Leon Berard

Lyon, France

Location

Hopital Prive Jean Mermoz

Lyon, France

Location

Centre Hospitalier Annecy Genevois

Pringy, France

Location

Centre Hospitalier Universitaire de Saint Etienne

Saint-Etienne, France

Location

Clinique Charcot

Sainte-Foy-lès-Lyon, France

Location

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MeSH Terms

Interventions

Trastuzumab; Paclitaxel; pegfilgrastim

Intervention Hierarchy (Ancestors)

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

Study Officials

• Olivier TREDAN, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 4, 2018
• First Posted: June 27, 2018
• Study Start: August 6, 2018
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

FR (9)