E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2 Positive Early Breast Cancer |
|
E.1.1.1 | Medical condition in easily understood language |
HER2 Positive Early Breast Cancer |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 compare the treatment effect of ABP 980 with trastuzumab on pathologic complete response (pCR) in women with early breast cancer
|
|
E.2.2 | Secondary objectives of the trial |
To assess the safety, tolerability, and immunogenicity of ABP 980 compared with trastuzumab
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Females ≥ 18 years of age
Histologically confirmed invasive breast cancer
Planning for surgical resection of breast tumor and sentinel node (SN) or axillary lymph node resection
Planning neoadjuvant chemotherapy
HER2 positive disease defined as:
3+ overexpression by immunohistochemistry (IHC) or
HER2 amplification by fluorescence in situ hybridization (FISH)
Measurable disease (assessment method used in order of priority: ultrasound, mammography, MRI, or physical examination) in the breast after diagnostic biopsy, defined as longest diameter ≥ 2.0 cm
Known ER and PR hormone receptor status at study entry
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Left ventricular ejection fraction (LVEF) of ≥ 55% by 2D echocardiogram
Normal bone marrow function as defined by:
absolute neutrophil count (ANC) > 1.5 x 10^9 g/dL (1,500/µL);
platelets > 100 x 10^9 g/dL (100,000/µL);
hemoglobin > 10.0 g/dL.
Normal hepatic function as defined by:
total bilirubin within normal institutional limits;
aspartate aminotransferase (AST) and alanine aminotransferase (ALT);
< 2.5 × the upper limit of normal (ULN);
subjects with an elevated unconjugated bilirubin (Gilbert's syndrome) will be eligible if hepatic enzymes and function are otherwise within normal limits (ie, AST, ALT, and Alkaline Phosphatase are within normal limits), and there is no evidence of hemolysis.
Normal renal function as defined by creatinine < 1.5 × ULN or estimated creatinine clearance (CrCl) ≥ 50 mL/min calculated by the Cockcroft-Gault method
Subjects must sign an IRB/EC-approved informed consent form before any study specific procedures
|
|
E.4 | Principal exclusion criteria |
Bilateral breast cancer
Presence of known metastases
Received prior treatment, including chemotherapy, biologic therapy, radiation or surgery with the exception of diagnostic biopsy for primary breast cancer
Other concomitant active malignancy or history of malignancy in the past 5 years except treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
Pre-existing clinically significant (≥ grade 2) peripheral neuropathy
Any history of documented or current congestive heart failure, current high-risk uncontrolled arrhythmias, current angina pectoris requiring a medicinal product, current clinically significant valvular disease, current evidence of transmural infarction on electrocardiogram (ECG), or current poorly controlled hypertension
Severe dyspnea at rest requiring supplementary oxygen therapy
History of positivity for hepatitis B surface antigen, hepatitis C virus, or HIV
Recent infection requiring a course of systemic anti-infectives that were completed
≤ 14 days before enrollment (with the exception of uncomplicated urinary tract infection)
Woman of childbearing potential who is pregnant or is breast feeding
Woman of childbearing potential who is not consenting to use highly effective methods of birth control (eg, true abstinence [periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception], sterilization, or other non-hormonal forms of contraception) during treatment and for al least 7 months after the last administration of the protocol specified treatment
Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study
Other investigational procedures while participating in this study are excluded
Subject has known sensitivity to any of the products to be administered during the study, including mammalian cell derived drug products, trastuzumab, murine proteins, or to any of the excipients
Subject previously has enrolled and/or has been randomized in this study
Subject likely to not be available to complete all protocol required study visits or procedures
History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Co-Primary Efficacy Criteria:
Risk difference (RD) of the incidence of pathologic complete response (pCR) in breast tissue and axillary lymph nodes
Risk ratio (RR) of the incidence of pathologic complete response (pCR) in breast tissue and axillary lymph nodes |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 10 (Initiation of investigational product adjuvant therapy cycle 1): Subjects will undergo a lumpectomy or mastectomy with sentinel node or axillary node dissection. Surgery is expected to be scheduled within 3 to 7 weeks after the last dose of investigational product in the neoadjuvant phase and pCR will be analyzed.
|
|
E.5.2 | Secondary end point(s) |
Risk diffenence (RD) of pCR in breast tissue
Risk ratio (RR) of pCR in breast tissue
Risk difference (RD)of pCR in breast tissue and axillary lymph nodes and absence of Ductal Carcinoma in Situ (DCIS)
Risk ratio (RR) of pCR in breast tissue and axillary lymph nodes and absence of Ductal Carcinoma in Situ (DCIS)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 10 (Initiation of investigational product adjuvant therapy cycle 1): Subjects will undergo a lumpectomy or mastectomy with SN or axillary node dissection. Surgery is expected to be scheduled within 3 to 7 weeks after the last dose of investigational product in the neoadjuvant phase Pathology of tumor sample and pCR will then be analyzed.
|
|
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 | Yes |
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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
ADA - anti-drug antibody testing is being performed |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 | No |
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 |
Belarus |
Brazil |
Bulgaria |
Canada |
Chile |
Czech Republic |
Germany |
Greece |
Hungary |
Italy |
Mexico |
Peru |
Poland |
Romania |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Ukraine |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The end of study (end of trial) will be the date when the last subject has their last study assessment |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |