Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Multicenter Phase III Study to Assess the Efficacy of Paclitaxel Versus Irinotecan in Patients With Recurrent or Metastatic Gastric Cancer Who Progress Following First-line Therapy
Brief Summary: The primary objectives of this study is to compare the efficacy of paclitaxel monotherapy with irinotecan monotherapy as defined by progression-free survival (PFS), in all patients with recurrent and metastatic gastric cancer who progress following first line therapy.


Options:
A: 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 contained 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 potential 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.

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, dementia 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
* Treatment within any other clinical trial parallel to the treatment phase of the current study 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 investigational product or confuse the assessment of study results
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or to any excipients
* History of allergic reactions attributed to compounds of similar chemical composition to capecitabine, 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 investigational medicinal product
B: Inclusion criteria:

* Histologically proven gastric adenocarcinoma, including adenocarcinoma of the gastro-oesophageal junction
* Metastatic or locally recurrent disease
* Prior adjuvant (and/or neo-adjuvant) chemotherapy with 5-Fluorouracil, Cisplatin, epirubicin is allowed provided that the patient has relapsed \> 12 months after the end of the chemotherapy
* Performance status Karnofsky index \> 70
* Hematology within 7 days before randomization:Hemoglobin ≥10g/dl, Absolute Neutrophil Count ≥2.0 10\^9/L, platelets ≥100 x 10\^9/L
* Blood chemistry within 7 days before randomization:Total bilirubin ≤1x Upper Normal Limit(UNL), Aspartate Aminotransferase (AST) Serum Glutamic Oxaloacetic Transaminase SGOT) and Alanine Aminotransferase (ALT)Serum Glutamate Pyruvate Transaminase(SGPT) ≤2.5xUNL, alkaline phosphatase ≤ 5x UNL, provided that AST or ALT \> 1.5 x UNL is not associated with alkaline phosphatase \> 2.5 x UNL; creatinine ≤1.25x UNL or 1.25x UNL \< creatinine ≤1.5x UNL and calculated/measured creatinine clearance ≥60 ml/min)
* Measurable and/or evaluable metastatic disease

Exclusion criteria:

* Any prior palliative chemotherapy
* Neurosensory symptoms National Cancer Institute Common Toxicity Criteria for Adverse Events grade≥2

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
C: Inclusion Criteria:

* Histologically confirmed gastric adenocarcinoma in tissue/cell
* Recurrent or metastatic gastric cancer that has progressed following first- line therapy
* Patients must be ≥18 years of age.
* ECOG performance status ≤ 2
* At least one lesion (measurable or non-measurable but evaluable) according to RECIST criteria
* Normal organ and bone marrow function measured within 2 weeks prior to administration of study treatment as defined below: Haemoglobin ≥ 9.0 g/dL White blood cells (WBC) ≥ 3000/µL Absolute neutrophil count (ANC) ≥ 1500/µL Platelet count ≥ 100 x 103/µL Total bilirubin ≤ 1.5 x upper normal limit (UNL) Creatinine clearance ≥ 60 ml/min or Serum creatinine ≤ 1.5 x UNL AST (SGOT)/ALT (SGPT) ≤ 2.5 x UNL unless liver metastases are present in which case it must be ≤ 5x UNL
* Life expectancy ≥ 12 weeks.
* Written informed consent
* Provision of informed consent for genetic research (In case of optional genetic research)

Exclusion Criteria:

* More than one prior chemotherapy regimen for the treatment of gastric cancer in the metastatic or recurrent setting.
* Treatment with any investigational product during the last 14 days (or a longer period depending on the defined characteristics of the agents used).
* Any previous treatment with a taxane, including paclitaxel and docetaxel or irinotecan, in the metastatic or recurrent setting.
* Patients with second primary cancer, except: adequately treated non- melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥5 years.
* Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used).
* Ongoing toxicities (\>CTCAE grade 2) caused by previous cancer therapy.
* Clinically proven gastric outlet obstruction or CTCAE grade 3 or grade 4 upper GI bleeding
* Medically uncontrolled, clinically significant heart disease or infection
* Patients with symptomatic uncontrolled brain metastases.
* Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
* Women who have pregnancy potential or willing to pregnant. Pregnant and breastfeeding women.
* Others Poor medical risk due to a serious, uncontrolled medical disorder, non- malignant systemic disease or active, uncontrolled infection Any psychiatric disorder that prohibits obtaining informed consent and regular follow-up. Inappropriate patient for subjects of this study on investigator's judgment
D: Inclusion Criteria:

* Histologically or cytologically confirmed locally advanced (unresectable) or metastatic adenocarcinoma of gastric or gastroesophageal junction
* Failed to only one systemic chemotherapy for locally advanced or metastatic disease, including patients whose diseases recur within 6 months after (neo)adjuvant chemotherapy. Chemotherapy administered with concurrent radiotherapy is NOT considered as systemic chemotherapy.
* Have at least one measurable lesion according to the RECIST criteria
* Aged above or equal to 18 years, at the time of acquisition of informed consent
* With ECOG performance status 0, 1, or 2
* Life expectancy equal to or more than 3 months
* With adequate organ and marrow function as defined below:
* With ability to understand and the willingness to sign a written Informed Consent Form

Exclusion Criteria:

* Had systemic chemotherapy within 3 weeks before the commencement of study treatment
* Had radiotherapy within 4 weeks before the commencement of study treatment
* With known brain metastasis
* With active multiple cancers or had treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer
* With prior irinotecan or taxane (paclitaxel, docetaxel) treatment
* Have received irradiation affecting \> 30% of the active bone marrow
* Had major surgery within 4 weeks of the start of study treatment (laparotomy, line placement is not considered major surgery)
* Have not recovered from prior treatments
* With preexisting peripheral neuropathy \> grade 2
* With history of allergic reaction to liposome product or other drugs formulated with polysorbate
* With uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, active gastrointestinal bleeding, watery stools, central nervous system disorders or psychiatric illness/social situation that would limit compliance with study requirements or judged to be ineligible for the study by the investigator
* Have received any investigational agents within 3 weeks preceding the start of study treatment
* Pregnant or breastfeeding females (a pregnancy test must be performed on all female patients who are of child-bearing potential before entering the study, and the result must be negative)
* With intestinal obstruction
* Have received St. John's Wort, CYP3A4 inducing anticonvulsants (phenytoin, phenobarbital, and carbamazepine), rifampin and rifabutin within two weeks, or ketoconazole, itraconazole, troleandomycin, erythromycin, diltiazem and verapamil within one week before the administration of study medications

Answer: C