Untreated invasive breast carcinoma eligible for primary definitive surgery (Stage I-IIIA) MedDRA version: 14.1 Level: PT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Tyverb
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Lapatinib
Other descriptive name: LAPATINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration
Sponsors
SOLTI
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the ability of the PAM50 HER2-enriched (HER2-E) subtype to predict pathological complete response in the breast (pCRB) to dual HER2 blockade with lapatinib and trastuzumab, with or without endocrine therapy, at the time of surgery.;Secondary Objective: -To evaluate the ability of the PAM50 HER2-E to predict pCR in the breast and axilla to dual HER2 blockade with lapatinib and trastuzumab, +/- endocrine therapy (ET), at the time of surgery. -To evaluate the ability of the PAM50 HER2-E to predict residual cancer burden in the breast to dual HER2 blockade with lapatinib and trastuzumab, +/- ET, at the time of surgery. -To evaluate if the hormone receptor (HR)?positive, PAM50 non-Luminal A/B (combined) subtypes benefit from dual HER2 blockade + ET, as measured by the changes in the % of Ki67-positive cells from Day 0 to Day 14 of treatment. -To identify gene expression changes from Day 0 to Day 14 after dual HER2 blockade. -To evaluate if the correlation to the PAM50 HER2-E centroid, as a continuous variable, predicts pCR and/or RCB in the breast to dual HER2 blockade with lapatinib and trastuzumab at the time of surgery.;Primary end point(s): Comparison between the PAM50 HER2-enriched versus non HER2-enriched cases to achieve pCRB from dual HER2 blockade with lapatinib and trastuzumab at the time of surgery.;Timepoint(s) of evaluation of this end point: After the surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Comparison between the PAM50 HER2-enriched versus non HER2-enriched cases to achieve pCR in the breast and axilla from dual HER2 blockade with lapatinib and trastuzumab at the time of surgery.;Timepoint(s) of evaluation of this end point: After the surgery | — |
Countries
Austria, Spain
Contacts
Public ContactOficina Operaciones
SOLTI
Outcome results
None listed