Gastric Cancer, cancer of the oesophago-gastric junction, esophageal cancer MedDRA version: 9.1 Level: LLT Classification code 10017758 Term: Gastric cancer MedDRA version: 9.1 Level: LLT Classification code 10015362 Term: Esophageal cancer
Conditions
Interventions
Trade Name: Tyverb
Product Name: Lapatinib
Product Code: GW572016
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: L01XE07
Sponsors
University Hospital of Heidelberg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed adenocarcinoma of the stomach, including adenocarcinoma of the gastroesophageal junction and esophagus • Metastatic disease • Measurable disease (according to RECIST criteria) • At least one prior chemotherapy for metastatic disease with progression during or no later than 6 months after last administration of chemotherapy. Chemotherapy must have con¬tained a platinum compound (cisplatin or oxaliplatin) • Her2 overexpression measured by FISH (amplification or increased gene copy number). Immunohistochemistry (ICH) 3+ can be included in case of an uncertain FISH test. • Patient willing to allow for biomarker analyses on his tumor tissue. • Written informed consent given prior to any protocol specific procedures according to the local regulatory requirements • Age >= 18 years • Eastern Cooperative Oncology Group Performance Status (ECOG-PS) = 2 • Life expectancy > 3 months • Adequate hematological, hepatic and renal function defined by: Hematology: Neutrophils >1.5x109/L; Platelets >100x109/L; Hemoglobin >8g/dL Hepatic function: Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Previous non curatively treated malignant disease other than the current gastroesophageal cancer with a disease-free survival of less than 5 years • History of significant neurological or psychiatric disorders including psychotic disorders, de¬mentia or seizures that would prohibit the understanding and giving of informed consent • History of active Hepatitis B or C or history of an HIV infection • Active uncontrolled infection • Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to randomisation. • Concurrent treatment with any other anti-cancer drug. • Presence of other medication that may interfere with study treatment or the action of the investi¬gational product or confuse the assessment of study results • History of allergic reactions attributed to compounds of similar chemical or biologic composi¬tion to lapatinib or to any excipients • History of allergic reactions attributed to compounds of similar chemical composition to cape¬citabine, fluorouracil or to any excipients • Known DPD deficiency • Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors • Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) • Active cardiac disease, defined as: • History of uncontrolled or symptomatic angina • History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation • Myocardial infarction New York Heart Association score 2) • Ejection fraction below the institutional normal limit • Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient • Pregnancy and lactation • History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investiga¬tional medicinal product • Participation in another clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective is to evaluate the anti-tumor efficacy of lapatinib plus capecitabine or lapatinib alone in patients with ErbB2 positive locally advanced or metastatic gastric adenocarcinoma or adenocarcinoma of the esophagus or gastro-esophageal junction.; Secondary Objective: Secondary objectives include: • the evaluation of the survival and safety parameters • the definition of biomarkers that are associated with response or resistance to treatment (Biomarker analysis) , e.g.: • Expression level of the EGF receptor by immunohistochemistry (IHC) and the gene copy number of the EGFR gene by fluorescence in situ hybridization (FISH). • Definition of activating or deactivating mutations of molecules with a functional role in the EGFR/Her2 dependent downstream signalling cascade like k-ras, b-raf or PTEN. • Detection of the truncated form of the Her2 receptor (p95HER2) by a paraffin-based immunofluorescence assay. • The detailed biomarker analysis plan will be updated according to novel findings in tumor models and translational studies in other tumor entities. The minimal goal at this stage will be to obtain tumor tissue samples from all patients included into the study protocol. ;Primary end point(s): Objective response rate (ORR, complete and partial remission according to RECIST criteria (Eisenhauer et al, 2009) – all to be confirmed by at least two consecutive tumor response assess¬ments within no shorter than 4 weeks) | — |
Countries
Germany
Outcome results
None listed