E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastric Cancer, cancer of the oesophago-gastric junction, esophageal cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015362 |
E.1.2 | Term | Esophageal cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 <=1.5xULN; ASAT (SGOT) and ALAT (SGPT) <= 2.5xULN; Alkaline phosphatase <5xULN. Renal function: The calculated creatinine clearance should be ≥60 mL/min • Eligibility of patients receiving medications or substances known to affect, or with the poten¬tial to affect the activity or pharmacokinetics of lapatinib will be determined following review of their use by the local Principal Investigator. A list of medications and substances known or with the potential to interact with CYP450 isoenzymes is provided in: Cytochrome P-450 Enzymes and Drug metabolism. In: Lacy CF, Armstrong LL, Goldman MP, Lance LL eds. Drug Information Handbook 8TH ed. Hudson, OH; LexiComp Inc. 2000: 1364-1371 • Able to swallow and retain oral medication • Negative pregnancy test (urine or serum) within 28 days prior to randomization for all women of childbearing potential (has to be verified within 7 days prior to randomization and during the study according the judgement of the investigator) • Willingness to perform double-barrier contraception during study and 6 months after end of treatment • Ability to understand and the willingness to sign a written informed consent document • Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
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E.4 | Principal 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 < 6 months from randomization • Uncontrolled or symptomatic congestive heart failure (> 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.
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E.5 End points |
E.5.1 | 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) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Pick the winner parrallel groups |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |