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The trial is designed to determine the efficacy and safety of ABP 980 compared with Trastuzumab in subjects with HER2 positive early breast cancer

Phase 1
Conditions
HER2 Positive Early Breast Cancer
MedDRA version: 18.1Level: PTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2012-004319-29-DE
Lead Sponsor
Amgen Inc.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Female
Target Recruitment
768
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

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 657
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 111

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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To compare the treatment effect of ABP 980 with trastuzumab on pathologic complete response (pCR) in women with early breast cancer<br>;Secondary Objective: To assess the safety, tolerability, and immunogenicity of ABP 980 compared with trastuzumab<br>;Primary end point(s): Co-Primary Efficacy Criteria:<br><br>Risk difference (RD) of the incidence of pathologic complete response (pCR) in breast tissue and axillary lymph nodes<br><br>Risk ratio (RR) of the incidence of pathologic complete response (pCR) in breast tissue and axillary lymph nodes;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. <br>
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): Risk diffenence (RD) of pCR in breast tissue<br><br>Risk ratio (RR) of pCR in breast tissue<br><br>Risk difference (RD)of pCR in breast tissue and axillary lymph nodes and absence of Ductal Carcinoma in Situ (DCIS)<br><br>Risk ratio (RR) of pCR in breast tissue and axillary lymph nodes and absence of Ductal Carcinoma in Situ (DCIS)<br>;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. <br>
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