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HER2-positive Breast CancerPhase 2BREASTIMMU02NCT03571633

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

A Phase 2 study testing Trastuzumab + Paclitaxel and Pegfilgrastim in people with HER2-positive Breast Cancer and Operable Breast Cancer, run by Centre Leon Berard at 9 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Trastuzumab + Paclitaxel and Pegfilgrastim
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
9 sitesFrance
Study dates
6 Aug 2018to Sep 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 13Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

France9 sites

  • Institut Sainte Catherine

    Avignon

  • CHRU Besançon

    Besançon, 25000

  • Centre de Lutte contre le Cancer Jean Perrin

    Clermont-Ferrand, 63000

  • Groupe Hospitalier Mutualiste de Grenoble

    Grenoble, 38000

  • Centre Leon Berard

    Lyon

  • Hopital Prive Jean Mermoz

    Lyon

  • Centre Hospitalier Annecy Genevois

    Pringy

  • Centre Hospitalier Universitaire de Saint Etienne

    Saint-Etienne

  • Clinique Charcot

    Sainte-Foy-lès-Lyon

Other trials in France

About this study

Official title: 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.

Read the 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

Being tested
Trastuzumab + Paclitaxel, Pegfilgrastim
Keywords
Pegfilgrastim, Trastuzumab/Paclitaxel, Antibody-dependent cell-mediated cytotoxicity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trastuzumab + PaclitaxelDrug

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

  • PegfilgrastimDrug

    Also called Neulasta

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

Study groups in NCT03571633
Study groupRoleWhat they receive
Paclitaxel+Trastuzumab+PegfilgrastimExperimentalNEOADJUVANT 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)
Receives: Drug: Trastuzumab + Paclitaxel; Drug: Pegfilgrastim
Paclitaxel+TrastuzumabActive comparatorNEOADJUVANT 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)
Receives: Drug: Trastuzumab + Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 16 weeks after start of treatment

Secondary outcomes (4)

  1. Disease Free survival

    From the date of randomisation until the date of event defined as the first documented relapse after surgery or death from any cause.

    Measured: At least 15 months following randomisation

  2. Time to relapse

    From the time of treatment start until the first documented relapse

    Measured: At least 15 months following randomisation

  3. Overall survival

    From the date of randomisation to the date of death from any cause

    Measured: At least 15 months following randomisation

  4. Adverse events reporting

    Based mainly on the frequency of AE graded according to the common toxicity criteria grading system (CTCAE-V4.03).

    Measured: At least 15 months following randomisation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2018
  2. Study start6 Aug 2018
  3. Primary completionJan 2027 (estimated)
  4. Study completionSep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03571633
Sponsor's protocol ID
ET17-057
Other IDs
2017-002069-22, 2017
Acronym
BREASTIMMU02
Status last verified
Nov 2025
First submitted
4 Jun 2018
Last updated
26 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010 Dec 15;127(12):2893-917. doi: 10.1002/ijc.25516.

    PubMed 21351269

  • Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF; American Society of Clinical Oncology; College of American Pathologists. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013 Nov 1;31(31):3997-4013. doi: 10.1200/JCO.2013.50.9984. Epub 2013 Oct 7.

    PubMed 24101045

  • Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF; American Society of Clinical Oncology/College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131(1):18-43. doi: 10.5858/2007-131-18-ASOCCO.

    PubMed 19548375

  • Zhou BP, Hung MC. Dysregulation of cellular signaling by HER2/neu in breast cancer. Semin Oncol. 2003 Oct;30(5 Suppl 16):38-48. doi: 10.1053/j.seminoncol.2003.08.006.

    PubMed 14613025

  • Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. doi: 10.1056/NEJMoa0910383.

    PubMed 21991949

  • Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, Bauerfeind I, Hilfrich J, Eidtmann H, Gerber B, Hanusch C, Kuhn T, du Bois A, Blohmer JU, Thomssen C, Dan Costa S, Jackisch C, Kaufmann M, Mehta K, von Minckwitz G. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010 Apr 20;28(12):2024-31. doi: 10.1200/JCO.2009.23.8451. Epub 2010 Mar 22.

    PubMed 20308670

  • Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010 Jan 30;375(9712):377-84. doi: 10.1016/S0140-6736(09)61964-4.

    PubMed 20113825

  • Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, Moliterni A, Vazquez F, Byakhov MJ, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Magazzu D, Heinzmann D, Steinseifer J, Valagussa P, Baselga J. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014 May;15(6):640-7. doi: 10.1016/S1470-2045(14)70080-4. Epub 2014 Mar 20.

    PubMed 24657003

  • Kute T, Stehle JR Jr, Ornelles D, Walker N, Delbono O, Vaughn JP. Understanding key assay parameters that affect measurements of trastuzumab-mediated ADCC against Her2 positive breast cancer cells. Oncoimmunology. 2012 Sep 1;1(6):810-821. doi: 10.4161/onci.20447.

    PubMed 23162748

  • Deauvieau F, Ollion V, Doffin AC, Achard C, Fonteneau JF, Verronese E, Durand I, Ghittoni R, Marvel J, Dezutter-Dambuyant C, Walzer T, Vie H, Perrot I, Goutagny N, Caux C, Valladeau-Guilemond J. Human natural killer cells promote cross-presentation of tumor cell-derived antigens by dendritic cells. Int J Cancer. 2015 Mar 1;136(5):1085-94. doi: 10.1002/ijc.29087. Epub 2014 Aug 6.

    PubMed 25046660

  • Hernandez-Ilizaliturri FJ, Jupudy V, Ostberg J, Oflazoglu E, Huberman A, Repasky E, Czuczman MS. Neutrophils contribute to the biological antitumor activity of rituximab in a non-Hodgkin's lymphoma severe combined immunodeficiency mouse model. Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):5866-73.

    PubMed 14676108

  • Cornet S, Mathe D, Chettab K, Evesque A, Matera EL, Tredan O, Dumontet C. Pegfilgrastim Enhances the Antitumor Effect of Therapeutic Monoclonal Antibodies. Mol Cancer Ther. 2016 Jun;15(6):1238-47. doi: 10.1158/1535-7163.MCT-15-0759. Epub 2016 Mar 17.

    PubMed 26988998

  • Cartron G, Zhao-Yang L, Baudard M, Kanouni T, Rouille V, Quittet P, Klein B, Rossi JF. Granulocyte-macrophage colony-stimulating factor potentiates rituximab in patients with relapsed follicular lymphoma: results of a phase II study. J Clin Oncol. 2008 Jun 1;26(16):2725-31. doi: 10.1200/JCO.2007.13.7729. Epub 2008 Apr 21.

    PubMed 18427151

  • Bossuyt V, Provenzano E, Symmans WF, Boughey JC, Coles C, Curigliano G, Dixon JM, Esserman LJ, Fastner G, Kuehn T, Peintinger F, von Minckwitz G, White J, Yang W, Badve S, Denkert C, MacGrogan G, Penault-Llorca F, Viale G, Cameron D; Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration. Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration. Ann Oncol. 2015 Jul;26(7):1280-91. doi: 10.1093/annonc/mdv161. Epub 2015 May 27.

    PubMed 26019189

  • Lin Y, Kikuchi S, Obata Y, Yagyu K; Tokyo Research Group on Prevention of Gastric Cancer. Serum levels of transforming growth factor beta1 are significantly correlated with venous invasion in patients with gastric cancer. J Gastroenterol Hepatol. 2006 Feb;21(2):432-7. doi: 10.1111/j.1440-1746.2005.03939.x.

    PubMed 16509870

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trastuzumab + Paclitaxel and Pegfilgrastim in people with HER2-positive Breast Cancer and Operable Breast Cancer, run by Centre Leon Berard at 9 sites in France.

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 13 inclusion and 6 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: under way, not looking for participants, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in France. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological complete response rate (pCR) (time frame: 16 weeks after start of treatment). 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 NCT03571633, which also lists 20 linked publications.

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 26 Nov 2025.

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