Phase II Trial to Validate Markers for a Response Evaluation of a Combined Therapy in Patients With HER2+ Breast Cancer
Condition: Carcinoma, Ductal, Breast
MeSH terms: Carcinoma, Ductal; Carcinoma, Ductal, Breast
Intervention: Biopsy before and after three weeks of study treatment; paclitaxel; lapatinib; trastuzumab
Intervention description: Core biopsies for histological analyses, to be analysed by the central pathology
Intervention MeSH terms: Paclitaxel; Trastuzumab; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: Female
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Unilateral primary invasive carcinoma of the breast

Summary:

      The Neo-PREDICT-HER2 Study is phase II trial to validate predictive markers for the response
      evaluation of a combined chemo-immunotherapy in patients with HER2-positive early breast
      cancer. The only treatment arm consists of Paclitaxel 80 mg/m2 weekly for 12 weeks with
      lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12
      weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Female patients, age at diagnosis 18 - 75 years

          2. Histological confirmed unilateral primary invasive carcinoma of the breast

          3. Clinical Stage Tumor 1 (cT1) (> 1 cm) - Clinical Stage Tumor 4 (cT4) (if operable,
             inflammatory breast cancer is excluded)

          4. HER2 over-expressing tumor confirmed by: 3+ by Immuno-histochemistry (IHC) and/or
             HER2/neu gene amplification by fluorescence, chromogenic or silver in-situ
             hybridization [Fluorescent In-Situ Hybridization (FISH), Chromogenic In-Situ
             Hybridization (CISH) or Silver In-Situ Hybridization (SISH); > 6 HER2 gene copies per
             nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals)
             of ≥ 2.0]

          5. Clinically node positive disease or node negative disease

          6. No clinical evidence for distant metastasis (cM0) after conventional staging

          7. Performance Status Eastern Cooperative Oncology Group (ECOG) ≤ 1 or Karnofsky Index
             (KI) ≥ 80%

          8. Baseline Left Ventricular Ejection Fraction (LVEF) > 50% measured by echocardiography

          9. Negative pregnancy test (urine or serum) within 7 days prior to start of induction
             treatment in premenopausal patients

         10. The patient must be accessible for treatment and follow-up

         11. Written informed consent including a written informed consent for shipping of tumor
             block for central pathology review and evaluation prior to the start of any study
             procedures

        Exclusion Criteria:

          1. Known hypersensitivity reaction to the compounds or incorporated substances

          2. Known polyneuropathy grade ≥ 2

          3. Have acute or currently active or requiring anti-viral therapy hepatic or biliary
             disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones,
             stable chronic liver disease per investigator assessment).

          4. Prior malignancy with a disease-free survival of < 10 years, except curatively treated
             basalioma of the skin, pTis of the cervix uteri

          5. Prior or concurrent treatment with cytotoxic agents for any reason after consultation
             with the sponsor

          6. Concurrent treatment with other experimental drugs. Participation in another clinical
             trial with any investigational not marketed drug within 30 days prior to study entry

          7. Male breast cancer

          8. Concurrent pregnancy; patients of childbearing potential must implement a highly
             effective (less than 1% failure rate) non-hormonal contraceptive measures during the
             study treatment

          9. Breast feeding women

         10. Sequential breast cancer

         11. Lack of patient compliance

         12. Inadequate organ function including:

               -  Leucocytes < 3.5 x 109/l

               -  Platelets < 100 x 109/l

               -  Absolute Neutrophil Count (ANC) < 1.5 x 109/l

               -  Hemoglobin < 9 g/dl

               -  Serum Creatinine > 1.5 mg/dl

               -  Serum Bilirubin > 1.1 mg/dl

               -  Alkaline phosphatase > 2.5 x Upper Limit of Normal (ULN)

               -  Aspartate Transaminase (ASAT) and/or Alanine Transaminase (ALAT) > 2.5 ULN

               -  Albumin < 2.5 g/dl

         13. Uncompensated cardiac function

         14. Malabsorption syndrome, disease significantly affecting gastrointestinal function

         15. Concomitant use of Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers