HER2-positive, estrogen receptor (ER)-negative/progesterone receptor (PR)-negative, node-negative early breast cancer
Conditions
Interventions
Trade Name: PHESGO
Product Name: FDC pertuzumab and trastuzumab with recombinant human hyaluronidase (rHuPH20)
Product Code: [RO7198574]
Pharmaceutical Form: Solution for injection/infusion
INN or Pro
Sponsors
Institut Jules Bordet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female. 2. Age =18 years old. 3. Eastern Cooperative Oncology Group (ECOG) performance status =1. (Appendix 1). 4. Subjects whose tumour measures =15 mm and =50 mm, according to clinical staging performed with imaging exams (either mammography, ultrasound or breast magnetic resonance imaging [MRI]). 5. Must have histologically confirmed diagnosis of HER2-positive and ER-negative/PR-negative breast cancer (analysis performed by the local laboratory). a. HER2-positive defined as a score of 3+ in IHC or a positive ISH (ratio of HER2 copy number/chromosome 17 =2 or average HER2 copy number =6 signals per cell). b. ER-negative/PR-negative defined as estrogen receptor and progesterone receptor nuclear staining 60 mL/min/1.73 m2 13. Completion of all necessary screening procedures within 28 days prior to enrolment. 14. Adequate cardiac function, defined as a left ventricular ejection fraction =55% estimated by echocardiogram (ECHO) or multiple-gated acquisition scintigraphy (MUGA). 15. Availability of a pre-treatment tumour biopsy sample as specified below: • At least one FFPE tumour block must be available for central evaluation. Whenever possible, two FFPE tumour blocks should be available (preferred). • If a block cannot be provided, 6 unstained FFPE slides of 10 µm thickness and 20 unstained FFPE slides of 4 µm thickness from the pre-treatment tumour biopsy must be provided as an alternative. These slides must be freshly cut prior the shipment to the sponsor • In either case, the local pathol
Exclusion criteria
Exclusion criteria: 1. Pregnant and/or lactating women. 2. Bilateral invasive breast cancer. 3. Evidence of metastatic breast cancer: all subjects must have had a CT/MRI scan of the thorax/abdomen/pelvis to rule out metastatic breast cancer prior to enrolment. FDG/PET-CT can be used as an alternative to replace all the exams above. A screening bone scan must have been done if ALP and/or corrected calcium levels were above the institutional upper limits at screening (if PET/CT was used as an alternative imaging exam, a bone scan and/or CT/MRI is not required). 4. Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the investigator’s opinion, may interfere with completion of the study. 5. Previous exposure to any anti-HER2 treatment. 6. Concomitant exposure to any investigational products as part of a clinical trial within 30 days prior to enrolment. 7. Subject with second primary malignancies diagnosed = 5 years before enrolment in the study. Exceptions are: adequately treated non-melanoma skin cancer, in situ cancer of the cervix, ductal carcinoma in situ of the breast, and any other solid or haematological tumour diagnosed > 5 years before enrolment and for which no chemotherapy and no systemic treatment were necessary, with no evidence of disease recurrence. 8. Resting electrocardiogram (ECG) with QTc >470 msec detected on at 2 or more time points within a 24-hour period, or family history of long QT syndrome. 9. Serious cardiac illness or medical conditions including, but not confined to, the following: • History of NCI CTCAE (v4) Grade ¿3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class ¿ II • High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate ¿ 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block, such as second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block) – Serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality • Angina pectoris requiring anti-anginal medication • Clinically significant valvular heart disease • Evidence of transmural infarction on ECG • Evidence of myocardial infarction within 12 months prior to randomization • Poorly controlled hypertension (i.e., systolic ¿ 180 mm Hg or diastolic ¿ 100 mmHg) 10. History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe LVSD, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome. 11. Peripheral neuropathy (CTCAE version 5) grade =2. 12. Major surgery within 14 days prior to enrolment. 13. Subject with HIV, Hepatitis B or Hepatitis C infection documented by serology, except for those subjects with a previous exposure to Hepatitis B who developed an effective immune response (HBSAg-negative and anti-HBS-positive). 14. Previous allogeneic bone marrow transplant. 15. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAE grade =3). 16. Subjects who received live attenuated vaccines within 14 days before enro
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate 3-year RFS in subjects with HER2-enriched, ER-negative/PR-negative, clinically node-negative breast cancers who achieve a pCR after neoadjuvant treatment with weekly paclitaxel (or docetaxel every 3 weeks) and dual HER2 blockade with pertuzumab and trastuzumab FDC SC;Secondary Objective: To evaluate 3-year RFS in all subjects with ER-negative/PR-negative, clinically node-negative breast cancers who achieve a pCR after neoadjuvant treatment with weekly paclitaxel (or docetaxel every 3 weeks) and dual HER2 blockade with pertuzumab and trastuzumab FDC SC.;Primary end point(s): 3-year RFS, defined as the time from enrolment until the first occurrence of one of the following events: Invasive ipsilateral breast tumour recurrence, local/regional invasive recurrence, distant recurrence, death from breast cancer, death attributable to any cause other than breast cancer, death from unknown cause; in subjects with HER2-enriched, ER-negative/PR-negative, clinically node-negative breast cancers who achieve a pCR after neoadjuvant treatment. ;Timepoint(s) of evaluation of this end point: end of trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 3-year RFS in all subjects who achieve a pCR.;Timepoint(s) of evaluation of this end point: end of trial | — |
Countries
Argentina, Australia, Belgium, Canada, Ireland, Israel, Italy, Korea, Republic of, New Zealand, Switzerland
Contacts
Public ContactRegulatory Office
International Breast Cancer Study Group IBCSG
Outcome results
None listed