Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase III Study of Gemcitabine/Oxaliplatin (GEMOX) With or Without Erlotinib in Unresectable, Metastatic Biliary Tract Carcinoma
Brief Summary: The purpose of this study is to determine whether Gemcitabine/Oxaliplatin (GEMOX) with or without Erlotinib (Tarceva) is effective in the treatment of unresectable, metastatic biliary tract carcinoma.


Options:
A: Inclusion Criteria:

1. Adenocarcinoma of the biliary tract (gallbladder, intra and/or extrahepatic bile ducts, or ampulla of Vater):

   * Cytologically or histologically confirmed. In case of uncertain biliary tract origin (e.g., intrahepatic, peripheral cholangiocarcinomas), inclusion is possible if i) extensive search for primary (thoracic and abdominopelvic CT scan, colonoscopy, upper digestive endoscopy, serum PSA level for men or mammography for women, and FDG-PET if possible) is negative; and ii) histological examination is consistent with bile duct adenocarcinoma (IHC should ideally be performed and be consistent with biliary primary, e.g., positive for cytokeratin 7 and 19 and negative for cytokeratin 20).
   * not amenable to curative resection, or recurrent after resection (i.e., locally advanced or metastatic),
   * With at least one unidimensionally measurable target lesion in a non-irradiated, non-PDT-treated area (longest diameter 1 cm \[spiral CT scan\]), or 2 cm \[conventional CT scan\]).
   * With biliary obstruction controlled,
2. Age between 18 and 75 years.
3. World Health Organization (WHO) performance status of 0 or 1.
4. Life expectancy higher than 3 months.
5. No prior chemotherapy for advanced disease. Previous adjuvant chemotherapy is allowed (completed at least 6 months previously, if containing gemcitabine or platinum salts). Previous irradiation (external radiotherapy, brachytherapy) and PDT are allowed provided that there is at least one unidimensionally measurable target lesion in untreated area.
6. Bilirubin 3 times the upper limit of the normal range (ULN). Pts with jaundice or evidence of bile duct obstruction, in whom the biliary tree can be decompressed by endoscopic or percutaneous endoprothesis with subsequent reduction in bilirubin £ 3 ULN, will be eligible for the study.
7. Aminotransferases (AST, ALT) 5 ULN, INR \< 1.5 (following vitamin K1 injection in patients with current or recent history of jaundice or bile duct obstruction), creatinine 1.5 ULN, neutrophils 1.5 109/L, platelets 100 109/L, hemoglobin 9 g/dL (red blood cell transfusion if needed is allowed).
8. Written informed consent. Note: EGFR tumor status has to be known for every pt, but it is neither an inclusion/exclusion criterion nor a stratification factor. EGFR expression has to be assessed by IHC using biopsy or surgical material, at any time prior to inclusion into the study.

Exclusion Criteria:

1. Known central nervous system metastases.
2. Contraindication or history of grade 3-4 allergy reaction to one treatment component.
3. Surgery (except diagnostic biopsy), external radiotherapy, brachytherapy, or PDT within 30 days prior to start of treatment. Prior adjuvant chemotherapy is only allowed if completed at least 30 days previously (6 months if containing gemcitabine or platinum salts).
4. Participation in another clinical trial within 30 days prior to start of treatment.
5. Concomitant systemic chronic immunotherapy, chemotherapy, or antitumor hormone therapy.
6. Previous administration of EGFR inhibitors or EGF.
7. Active uncontrolled infection, peripheral neuropathy grade 2, acute or subacute bowel obstruction or history of inflammatory bowel disease, symptomatic coronary disease or myocardial infarction in the past 6 months, congestive heart failure (NYHA class II), interstitial pneumonitis or respiratory failure, or renal failure.
8. Pregnancy (or positive b-HCG dosage at baseline), breast-feeding, or lack of effective contraception in male or female pts of reproductive potential.
9. Other malignancies either currently active or in the last 5 years, except adequately treated in situ carcinoma of the cervix and basal or squamous cell skin carcinoma.
10. Legal incapacity or physical, psychological or mental status interfering with the pt's ability to terminate the study or to sign the informed consent.
B: Inclusion Criteria:

* Histologically or cytologically-confirmed advanced (unresectable or metastatic) biliary tract cancer (gallbladder cancer, cancer of the extrahepatic bile duct, intrahepatic cholangiocarcinoma and ampullary carcinoma)
* Patients must have measurable or evaluable but non-measurable disease
* Chemotherapy-naïve (prior chemotherapy in the adjuvant setting completed more than 3 months before the trial entry is accepted).
* WHO performance status 0 to 2: patients must have a WHO PS ≤ 2

Exclusion Criteria:

* Patients must not have received prior systemic therapy for advanced (unresectable or metastatic) disease; prior chemotherapy in the adjuvant setting within 3 months before the trial entry is accepted
* Inadequate end-organ function or Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance wit
* Significant cardiovascular event (e.g. myocardial infarction, superior vena cava \[SVC\] syndrome, New York Heart Association \[NYHA\] classification of heart disease ³2) within 3 months before entry, or presence of cardiac disease that in the opinion of
* History of arrhythmia or QTc with Bazett's correction unmeasurable or ≥ 480 msec on screening ECG
C: Inclusion Criteria:

1. age ≥ 18
2. histologically or cytologically confirmed adenocarcinoma of biliary tract
3. unresectable or metastatic
4. ECOG performance status of 0\~2
5. measurable or evaluable lesion per RECIST criteria
6. adequate marrow, hepatic, renal and cardiac functions
7. no prior chemotherapy or molecularly targeted therapy for the advanced biliary carcinoma (prior adjuvant chemotherapy will be allowed if administered ≥ 6 months from the study entry)
8. provision of a signed written informed consent

Exclusion Criteria:

1. severe co-morbid illness and/or active infections
2. pregnant or lactating women
3. active CNS metastases not controllable with radiotherapy or corticosteroids
4. known history of hypersensitivity to study drugs
5. prior exposure to EGFR tyrosine kinase inhibitor
D: Inclusion criteria:

* Cyto-/histological confirmed unresectable, locally advanced, or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma or adenocarcinoma of gallbladder, but NOT other peri-ampulla Vateri or mixed tumor.
* At least one, not previously irradiated, measurable lesion according to RECIST (version 1.1).
* Eastern Cooperative Oncology Group (ECOG) performance score of 0-1.
* Aged no less than 20 years, at the time of acquisition of informed consent.
* Life expectancy \>= 3 months.
* Adequate organ and bone marrow function as defined below: WBC \>= 3.00 × 103/L and absolute neutrophil count \>= 1.50 × 103/L, Platelet count \>= 100 × 103/L, Hemoglobin level \>= 10 g/dL, Serum creatinine \<= 1.5 x Upper Normal Limit (UNL) and calculated GFR \>= 40mL/min, Serum bilirubin \<= 1.5 x UNL , ALT \<= 2.5x UNL.
* Ability to understand and willingness to sign written Informed Consent Form.

Exclusion criteria:

* Other anti-tumor agent such as systemic chemotherapy, immunotherapy or EGFR/VEGF-pathway-targeting therapy before the commencement of study treatment.
* Radiotherapy (except palliative irradiation of bone lesions) within 4 weeks before the commencement of study treatment.
* Other cancer or prior treatment for other carcinomas within the last five years, except cured non-melanoma skin cancer and treated in-situ cervical cancer.
* Known CNS metastasis.
* Major surgery within 4 weeks prior to start of study treatment (diagnostic biopsy, laparotomy, line placement is not considered as major surgery).
* Pre-existing peripheral neuropathy \>= grade 2.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction in the past 12 months, active gastrointestinal bleeding, 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.
* Having received any investigational agents or participated in any investigational drug study within 4 weeks prior to study enrollment.
* Pregnant or breast-feeding female (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).
* Poor compliance.

Answer: C