A randomised, multicentre, multinational Phase II study to evaluate pertuzumab in combination with trastuzumab given either concomitantly or sequentially with standard anthracycline based chemotherapy or concomitantly with a non-anthracycline based chemotherapy regimen, as neoadjuvant therapy for patients with locally advanced, inflammatory or early stage HER2-positive breast cancer

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2009-012019-17-PT
• Date of registration: 30/09/2009
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: A randomised, multicentre, multinational Phase II study to evaluate pertuzumab in combination with trastuzumab given either concomitantly or sequentially with standard anthracycline based chemotherapy or concomitantly with a non-anthracycline based chemotherapy regimen, as neoadjuvant therapy for patients with locally advanced, inflammatory or early stage HER2-positive breast cancer
• Scientific title: A randomised, multicentre, multinational Phase II study to evaluate pertuzumab in combination with trastuzumab given either concomitantly or sequentially with standard anthracycline based chemotherapy or concomitantly with a non-anthracycline based chemotherapy regimen, as neoadjuvant therapy for patients with locally advanced, inflammatory or early stage HER2-positive breast cancer
• Date of first enrolment: 05/03/2010
• Target sample size: 225
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012019-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Greece, Italy, Portugal, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Female patients with locally inflammatory or early stage, unilateral and histologically confirmed invasive breast cancer. The initial breast cancer asessment should be performed by a physician with experience in surgery for breast cancer. Patients with inflammatory breast cancer must be able to have a core needle biopsy.
2. Primary tumor > 2cm in diameter.
3. HER-pos breast cancer confirmed by a central laboratory. Tumors must be HER2 3+ by IHC or FISH/CISH +(FISH/CISH pos mandatory for HER 2 2+ tumors).
4. Availability of FFPE tissue for central confirmation of HER2 eligibility.
5. Female patients, age>=18 years.
6. Baseline LVEF>=55%.
7. Performance status ECOG<=1.
8. At least 4 weeks since major unrelated surgery, with full recovery.
9. A negative pregnancy test must be available for pre-menopausal women and for women less than 12 months after the onset of menopause.
10. For women of childbearing potential agreement to use a "highly effective" , non-hormonal form of contraception or two "effective" forms of non-hormonal contraception by the patient and/or partner. Contraception must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment.
11. Signed informed consent.







Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Metastatic disease (Stage IV) or bilateral breast cancer.
2. Previous anticancer therapy or radiotherapy for any malignancy.
3. Other malignancy, except for carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent.
4. Inadequate bone marrow function (e.g. Absolute Neutrophil Count (ANC) < 1.5 x 109/L, Platelet count < 100 x 109/L and Hb < 9 g/dL).
5. Impaired liver function: (e.g. serum [total] bilirubin > 1.25 x ULN (with the exception of Gilbert’s syndrome), AST, ALT > 1.25 x ULN, albumin < 25 g/L.
6. Inadequate renal function, serum creatinine > 1.5 x ULN.
7. Uncontrolled hypertension (systolic >150 and/or diastolic > 100), unstable angina, CHF of any NYHA classification, serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months of enrollment, or LVEF < 55%.
8. Dyspnea at rest or other diseases which require continuous oxygen therapy.
9. Severe uncontrolled systemic disease (e.g. hypertension, clinically significant cardiovascular, pulmonary, metabolic, wound-healing, ulcer, or bone fracture).
10. Patients with insulin-dependent diabetes.
11. Pregnant and/or lactating women.
12. Patients with reproductive potential not willing to use a ‘highly effective’ method of contraception or two ‘effective’ methods of contraception as described in General Inclusion Criterion number 10.
13. Received any investigational treatment within 4 weeks of study start.
14. Patients with known infection with HIV, HBV, HCV.
15. Current chronic daily treatment with corticosteroids (dose of >10 mg methylprednisolone, or equivalent [excluding inhaled steroids])
16. Known hypersensitivity to any of the study drugs or excipients.
17. Patients assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Locally advanced, inflammatory or early stage HER2 positive breast cancer
MedDRA version: 9.1 Level: LLT Classification code 10065430 Term: HER-2 positive breast cancer

Intervention(s)

Product Name: Pertuzumab (rhuMAb 2C4)
Product Code: RO4368451
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Pertuzumab
CAS Number: 380610-27-5
Current Sponsor code: Ro-4368451/F01
Other descriptive name: rhuMAb 2C4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 420-14

Trade Name: Herceptin
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Trastuzumab
CAS Number: 180288-69-1
Current Sponsor code: Ro 45-2317/V03
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Primary end point(s): The primary objective of the study is to describe the tolerability of the treatment regimens in Arms A, B and C during neoadjuvant treatment. The primary endpoint of this study therefore does not relate to efficacy. The following safety endpoints are considered of primary importance for the evaluation of the primary objective:
– Incidence of symptomatic cardiac events as assessed by the Investigator (Grade 3, 4 or 5 symptomatic LVSD)
– LVEF measures over the course of the neoadjuvant period (LVEF decline of =10% from baseline and to a value of <50%)

Main Objective: To make a preliminary assessment of the tolerability of neoadjuvant treatment with one of the following treatment regimens:
Arm A
FEC->T with trastuzumab and pertuzumab given from the start of the chemotherapy regimen (i.e. concurrently with the anthracycline)
OR
Arm B
FEC->T with trastuzumab and pertuzumab given from the start of the taxane treatment (i.e. following the anthracycline)
OR
Arm C
TCH with pertuzumab, with both antibodies being given from the start of the chemotherapy.
The primary objective will be evaluated when all patients have received six cycles of neoadjuvant treatment, had their surgery and all necessary samples taken or withdrawn from the study whichever is earlier.

Secondary Objective: •To make a preliminary assessment of the activity associated with each regimen as indicated by the complete pathological response (pCR) rate.
•To evaluate the safety profiles of each treatment regimen, including pre-operative (neoadjuvant) and post-operative (adjuvant) treatment.
•To investigate the overall survival, the time to clinical response, time-to-response, disease free survival and progression free survival for each treatment arm.
•To investigate the biomarkers that may be associated with primary and secondary efficacy endpoints in accordance with each treatment arm.
•To investigate the rate of breast conservative surgery for all patients with T2-3 tumors for whom mastectomy was planned at diagnosis.
An overall assessment of the risk and benefit of each regimen will be made.

Secondary ID(s)

2009-012019-17-IT

BO22280