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

  • STATUS
    Recruiting
  • End date
    Apr 9, 2022
  • participants needed
    90
  • sponsor
    Centre Leon Berard
Updated on 12 September 2021
platelet count
paclitaxel
cancer
cyclophosphamide
breast cancer
gilbert's syndrome
neutrophil count
HER2
trastuzumab
breast cancer staging

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.

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. Rseau rgional de Cancrologie, 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

Details
Condition HER2 Positive Breast Cancer, Operable Breast Cancer, her2/neu-positive breast cancer, her2-positive breast cancer
Treatment pegfilgrastim, Trastuzumab + Paclitaxel
Clinical Study IdentifierNCT03571633
SponsorCentre Leon Berard
Last Modified on12 September 2021

Eligibility

Yes No Not Sure

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](ftp://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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note