Assesment of response predictor genes in patients with initial breast cancer HER2+ to the lapatinib and trastuzumab treatment combination before surgery.

Phase 1

• Conditions: ntreated invasive breast carcinoma eligible for primary definitive surgery (Stage I-IIIA); MedDRA version: 14.1Level: 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: EUCTR2013-001036-22-ES
• Lead Sponsor: SOLTI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07-12
• Last Update Posted: 27 June 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 0

Inclusion Criteria

-Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures
-Untreated invasive breast carcinoma eligible for primary definitive surgery (stage I-IIIA)
-Histologically confirmed invasive breast carcinoma, with all of the following characteristics:
a.Primary tumor >=1cm in largest diameter
b.cN0-2
c.No evidence of distant metastasis (M0)
-HER2-positive invasive breast cancer, centrally determined and defined by CAP guidelines as:
* 3+ overexpression by IHC (uniform, intense membrane staining of >30% of invasive tumor cells)
or
* 2+ or 3+ (in 30% or less neoplastic cells) overexpression by IHC and HER2 gene amplification by in situ hybridization (ISH >6 HER2 gene copies per nucleus, or a ISH ratio [HER2 gene copies to chromosome 17 signals] of >2.2)
-Female patients
-Age >=18 years
-ECOG Performance Status of 0 or 1
-Adequate organ function defined as:
*Absolute neutrophil count (ANC) >=1.5 x 109/L
*Hemoglobin (Hgb) >=10 g/dL
*Platelets >100 000 /mm3
*Creatinine <=1.6 mg/dL
*ALT and AST <=2.5 x ULN
*Alkaline phosphatase ?5 ULN
*Total bilirubin <=1.5 mg/dL
-Baseline LVEF ?50% measured by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan
-Negative ?-HCG pregnancy test (serum) for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after the menopause. All subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control from 2 weeks before administration of the first dose of investigational product until 28 days after the last dose of investigational product
-Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
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 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

-Stage III inoperable breast cancer (e.g. T4 tumors and/or N3)
-Patients with locally advanced disease, or patients for whom upfront chemotherapy including taxanes and anthracyclines is clinically judged appropriate as optimal neoadjuvant treatment
-Prior chemotherapy, radiotherapy, or surgery for invasive breast cancer, other than excision of tumor in the contralateral breast, and provided that the patient did not previously receive adjuvant radiotherapy or chemotherapy
-Subjects with a concurrently active second malignancy, other than adequately treated non-melanoma skin cancers, in situ melanoma or in situ cervical cancer. Subjects with other non-mammary malignancies must have been disease-free for at least 5 years
-Known or suspected hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances
-Concurrent congestive heart failure or LVEF <50%
-Clinically significant (i.e. active) cardiovascular disease, including cerebrovascular accident (<6 months before enrollment), unstable angina pectoris, myocardial infarction ?6 months before enrollment, uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg) or high-risk uncontrolled arrhythmias
-Uncontrolled diabetes mellitus, active peptic ulcer disease, or uncontrolled epilepsy
-Active uncontrolled infection at the time of enrollment
-History of significant co-morbidities that, in the judgment of the investigator, may interfere with the conduction of the study, the evaluation of response, or with informed consent
-Use of any investigational agent or participation in another therapeutic clinical trial concurrently or in the previous 30 days before the enrollment
-Patients who are pregnant or breast-feeding
-Women of child bearing potential who are unable or unwilling to use contraceptive measures
-Inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee
-Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded
-Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy other than the trial therapies)
-Concomitant use of CYP3A4 inhibitors or inducers

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified