Male or female patients with locally recurrent or metastatic HER2-positive breast cancer who have relapsed early after adjuvant treatment that included trastuzumab and who have not received prior chemotherapy for their locally recurrent or metastatic disease MedDRA version: 9.1 Level: HLGT Classification code 10006291 Term: Breast neoplasms malignant and unspecified (incl nipple)
Conditions
Interventions
Trade Name: Herceptin
Product Code: RO045-2317
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Trastuzumab
CAS Number: 180288-69-1
Current Sponsor code: RO04
Sponsors
Roche Austria GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, age = 18 years. 2. Pathologically confirmed breast adenocarcinoma with measurable (per RECIST, see Appendix 2) or non-measurable, locally recurrent or metastatic lesions. 3. Documented HER2 protein overexpression as determined by immunohistochemistry (IHC) 3+ or by demonstrated HER2/c-erbB2 gene amplification according to fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH) of the primary tumor by a local or central laboratory. 4. Candidates for chemotherapy. Locally advanced disease must not be amenable to resection with curative intent. 5. Most recent prior systemic treatment for breast cancer was adjuvant therapy that included trastuzumab. Disease progression must have occurred during adjuvant treatment or up to 12 months from completion of adjuvant treatment. Radiotherapy may have been received after adjuvant therapy, however patients should have recovered from any acute reversible toxicity. 6. LVEF = 55% measured by either echocardiography or multiple gated nuclear angiography (MUGA) within 6 weeks of study treatment initiation. 7. ECOG Performance Status = 1 8. Able and willing to comply with the protocol. 9. Written informed consent, obtained prior to beginning 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Previous treatment for locally advanced or metastatic breast cancer other than radiotherapy. Patients must have fully recovered from side effects of any prior radiotherapy. 2. Prior treatment with bevacizumab or capecitabine. 3. Prior neoadjuvant or adjuvant treatment with anthracyclines if the maximum cumulative dose was greater than 360 mg/m2 of doxorubicin or 720 mg/m2 of epirubicin. 4. Chronic daily treatment with corticosteroids (dose of > 10 mg/day methylprednisolone equivalent) excluding inhaled steroids. 5. Chronic daily treatment with aspirin (>325 mg/day) or clopidogrel (> 75 mg / day). 6. Requirement for concurrent use of the antiviral agent sorivudine, or chemically related analogues, such as brivudine. 7. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to enrolment, or anticipation of the need for major surgery during the course of the study treatment. 8. Current or recent (within the 30 days prior to starting study treatment) treatment with another investigational drug or participation in another investigational study. 13. Other primary malignancy which could affect compliance with the protocol or interpretation of results. Patients treated with curative intent and disease-free for at least 5 years and patients treated curatively for carcinoma in situ of the cervix or non-melanomatous skin cancer may be included. 14. Evidence of CNS metastasis. If there is any clinical suspicion of brain metastasis, a computerized tomography (CT) scan or magnetic resonance imaging (MRI) of the brain must be conducted within 4 weeks prior to enrolment. 15. Evidence of spinal cord compression caused by metastases. 16. Serious concurrent disease which could affect compliance with the protocol or interpretation of results, including, but not limited to: 17. Active infection requiring IV antibiotics. 18. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg). 19. Clinically significant (i.e. active) cardiovascular disease as indicated by: cerebrovascular accident or stroke = 6 months prior to study entry; myocardial infarction = 6 months prior to study entry; unstable angina; New York Heart Association (NYHA) (see Appendix 4) Grade II or greater CHF; serious cardiac arrhythmia requiring medication; clinically significant valvular heart disease. 20. Dyspnea at rest necessitating supportive oxygen therapy or with significant pleural effusions. 21. Poorly controlled diabetes mellitus. 22. Cardiac toxicity during previous trastuzumab treatment that necessitated discontinuation of trastuzumab. 23. History or evidence upon physical/neurological examination of CNS disease unrelated to cancer (e.g. uncontrolled seizures) unless adequately treated with standard medical therapy. 24. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding. 25. History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months of study entry. 26. Serious non-healing wound, peptic ulcer, or bone fracture. 35. Pregnant or lactating females. For women of childbearing potential, serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate the following with 1) first-line trastuzumab/bevacizumab combination treatment and 2) with second-line combined trastuzumab/bevacizumab with chemotherapy (capecitabine or docetaxel) treatment: o Overall response rate (ORR) o Best overall response (OR) o Duration of response (DR) o PFS (first-line) o Safety and tolerability To evaluate the following for the study regimens combined (combined treatment with trastuzumab and bevacizumab with the addition of capecitabine or docetaxel at progression): o Overall survival (OS) o Safety and tolerability ;Primary end point(s): To evaluate progression free survival (PFS) following second-line therapy in patients who have received trastuzumab and bevacizumab as first-line treatment for metastatic or locally advanced breast cancer with chemotherapy (capecitabine or docetaxel) added to the regimen at first sign of progression (second-line therapy). ;Main Objective: To evaluate progression free survival (PFS) following second-line therapy in patients who have received trastuzumab and bevacizumab as first-line treatment for metastatic or locally advanced breast cancer with chemotherapy (capecitabine or docetaxel) added to the regimen at first sign of progression (second-line therapy). | — |
Countries
Austria
Outcome results
None listed