E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced, inflammatory or early stage HER2 positive breast cancer. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006200 |
E.1.2 | Term | Breast cancer stage II |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006201 |
E.1.2 | Term | Breast cancer stage III |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021974 |
E.1.2 | Term | Inflammatory breast cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
- 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 neo-adjuvant treatment of pertuzumab and docetaxel.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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). 6. Baseline LVEF of ≥ 55% (measured by echocardiogram or MUGA). 7. Performance status ECOG Scale ≤ 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 2 years after the onset of menopause. 10. Signed informed consent.
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E.4 | Principal 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 lest 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.
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E.5 End points |
E.5.1 | 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.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Evaluation of biomarkers for response prediction |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study will be five years after randomization of the last patient or progressive disease experienced in all patients, whichever is earlier. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |