A randomised, multicenter, multinational Phase II study on trastuzumab plus docetaxel versus trastuzumab plus docetaxel plus pertuzumab versus trastuzumab plus pertuzumab versus pertuzumab and docetaxel in patients with locally advanced, inflammatory or early stage HER2 positive breast cancer. - NEOSPHERE

• Register: EUCTR
• Last refreshed on: 24 November 2014
• Main ID: EUCTR2007-001105-13-AT
• Date of registration: 03/10/2007
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A randomised, multicenter, multinational Phase II study on trastuzumab plus docetaxel versus trastuzumab plus docetaxel plus pertuzumab versus trastuzumab plus pertuzumab versus pertuzumab and docetaxel in patients with locally advanced, inflammatory or early stage HER2 positive breast cancer. - NEOSPHERE
• Scientific title: A randomised, multicenter, multinational Phase II study on trastuzumab plus docetaxel versus trastuzumab plus docetaxel plus pertuzumab versus trastuzumab plus pertuzumab versus pertuzumab and docetaxel in patients with locally advanced, inflammatory or early stage HER2 positive breast cancer. - NEOSPHERE
• Date of first enrolment: 29/11/2007
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001105-13
• 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

Countries of recruitment

Austria, Italy, Poland, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Female patients =18 years with locally advanced, inflammatory or early
stage, unilateral and histologically confirmed invasive breast cancer.
2. Primary tumor >2cm in diameter.
3. HER2 positive confirmed by a central laboratory. Tumors must be HER2+++
by IHC or FISH/CISH + (FISH/CISH mandatory for HER2 ++ tumors).
4. Availability of FFPE tissue for central confirmation of HER2 eligibility (FFPE
tumor tissue will subsequently be used for assessing status of biomarkers).
5. Baseline LVEF of = 55% (measured by echocardiogram or MUGA).
6. Performance status ECOG Scale = 1.
7. At least 4 weeks since major unrelated surgery, with full recovery.
8. A negative pregnancy test must be available for pre-menopausal women and for
women less than 2 years after the onset of menopause.
9. 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 or basal cell
carcinoma.
4. Inadequate bone marrow function (e.g. Absolute Neutrophil Count (ANC)
<1.5 x 1,000,000,000/L, Platelet count < 100 x 1,000,000,000/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 (exception, 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 requires continuous oxygen therapy.
9. Severe uncontrolled systemic disease (e.g. hypertension, clinically significant
cardiovascular, pulmonary, metabolic, wound-healing, ulcer, or bone fracture).
10. Subjects with insulin-dependent Diabetes
11. Pregnant and/or lactating women.
12. Subjects with reproductive potential not willing to use highly effective non-hormonal method of contraception or two effective forms of non-hormonal contraception. Contraception use must continue for the duration of study treatment and for at least 6 months post discontinuation of study treatment. For details please see section 7.2.4.
13. Received any investigational treatment within 4 weeks of study start.
14. Subjects with known infection with HIV, HBV, HCV.
15. Known hypersensitivity to any of the study drugs or excipients.
16. Subjects 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
MedDRA version: 9.1 Level: LLT Classification code 10006200 Term: Breast cancer stage II
MedDRA version: 9.1 Level: LLT Classification code 10006201 Term: Breast cancer stage III
MedDRA version: 9.1 Level: LLT Classification code 10021974 Term: Inflammatory breast cancer

Intervention(s)

Product Name: Pertuzumab (rhuMAb 2C4)
Product Code: RO4368451
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Pertuzumab
Current Sponsor code: RO4368451
Other descriptive name: rhuMAb 2C4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 175 mg/7 ml-

Trade Name: Herceptin®
Product Code: Ro 45-2317
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
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Primary end point(s): The primary endpoint is post-surgery pathological complete response rate in the breast (pCR) evaluated after 4 cycles of treatment and surgery or withdrawn from the study whichever occurs sooner. A pathological complete response is defined at the time of surgery and the rate is the proportion of the intent-to-treat population that achieve a pCR.

Main Objective: To make a preliminary assessment of the efficacy of neoadjuvant treatment of trastuzumab and docetaxel as compared to trastuzumab, pertuzumab and docetaxel as compared to trastuzumab and pertuzumab and pertuzumab and docetaxel compared to trastuzumab, pertuzumab and docetaxel, in patients with T2-4d HER2 positive breast cancer, based on complete pathological response rate.

Secondary Objective: - To evaluate the safety profiles of each treatment regimen, including pre-operative
(neoadjuvant) and post-operative (adjuvant) treatment.
- To determine the time to clinical response, time-to-response, disease free survival
and progression free survival for each treatment arm.
- To evaluate the biomarkers that may be associated with primary and secondary
efficacy endpoints in accordance with each treatment arm.
- To evaluate the rate of breast conservative surgery for all patients with T2-3
tumors for whom mastectomy was planned at diagnosis.
- To make a preliminary assessment of the efficacy of neoadjuvant treatment of pertuzumab and docetaxel

Secondary ID(s)

2007-001105-13-ES

WO20697