Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II, Randomized, Open-Label Study of Cetuximab and Bevacizumab Alone or in Combination With Fixed-Dose Rate Gemcitabine as First-Line Therapy of Patients With Metastatic Adenocarcinoma of the Pancreas
Brief Summary: Eligible patients with metastatic pancreatic cancer will be treated with dual agent monoclonal antibody consisting of cetuximab and bevacizumab alone or in combination with gemcitabine


Options:
A: Inclusion Criteria:

* Age ≥ 18 years
* Histologically confirmed diagnosis of adenocarcinoma of the pancreas
* Locally advanced (non-resectable) or metastatic pancreatic cancer
* Presence of at least one uni-dimensional indicator lesion measurable by CT scan or MRI in not an irradiated area (RECIST criteria)
* Immunohistochemical evidence or positive EGFR expression prior to study entry in primary tumor and/or at least one metastasis
* Life expectancy of ≥ 3 months
* Karnofsky performance status of ≥70 at study entry
* Neutrophils ≥ 1.5 x 109/L, platelets ≥100 x 109/L, and hemoglobin ≥ 9 g/dL
* Bilirubin level either normal or \< 1.5 x ULN
* ASAT and ALAT ≤ 2.5 X ULN (≤ 5 x ULN if liver metastasis are present)
* Serum creatinine \< 1.5 x ULN
* Effective contraception for both, male and female patients if the risk of conception exists
* Signed written informed consents prior to beginning protocol specific procedures

Exclusion Criteria:

* Brain metastasis
* Previous chemotherapy for locally advanced or metastatic pancreatic cancer
* Adjuvant therapy is allowed if recurrence is documented \> 6 months after the end of adjuvant treatment
* Radiotherapy within 4 weeks prior to study entry
* Concurrent chronic systemic immune therapy
* Any investigational agent(s) 4 weeks prior to entry
* Previous exposure to EGF, monoclonal antibodies, signal transduction inhibitors or EGFR targeting therapy
* Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months
* Known grade 3 or 4 allergic reaction to any of the components of the treatment
* Known drug abuse/ alcohol abuse
* Legal incapacity or limited legal capacity
* Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent
* Women who are pregnant or breastfeeding
* Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial).
B: Inclusion Criteria:

1. Ability to understand and willingness to sign a written informed consent
2. Able, in the investigator's opinion, to fulfill the procedures and explorations of the study
3. Age ≥ 18 years old
4. ECOG 0-2
5. Life expectancy ≥ 12 weeks
6. Patients with metastatic adenocarcinoma of the pancreas, following 7th edition of TNM classification
7. Histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas
8. Measurable disease following RECIST criteria version 1.1
9. No previous systemic treatment for metastatic pancreatic cancer Adjuvant chemotherapy al least 6 months before enrollment is allowed. Patients having neoadjuvant chemotherapy must have completed the treatment at least 4 weeks before trial entry. Toxicities associated to previous treatment must be resolved before enrollment. Progression disease (metastatic disease) must be confirmed after adjuvant treatment
10. Adequate bone marrow function as determined by:

    * Hemoglobin: ≥ 9 g/dL. (patients with hemoglobin \< 9 g/dL could be transfused before their inclusion on the study)
    * Platelets: ≥ 100 x 109/L
    * Absolute Neutrophil account (ANC) ≥ 1,5 x 109/L
11. Adequate liver function, as determined by:

    * Serum bilirubin ≤ 1,5 x LSN
    * AST, ALT ≤ 2,5 x LSN in patients without liver metastasis. In patients with liver metastasis ≤ 5 x LSN
    * Alkaline phosphatase ≤ 2,5 x LSN or ≤ 5 x LSN in patients with liver metastasis. In patients with bone metastasis ≤ 10 x LSN
12. Adequate renal function, as determined by:

    * Creatinine clearance using the Cockcroft-Gault formula ≥ 50.0 ml/min
13. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to randomization. Postmenopausal women are defined as those who have been amenorrheic for at least 12 months. Also, both men and women enrolled in this study must use adequate birth control (eg., abstinence, intrauterine device, oral contraceptive or double barrier method or be surgically sterile), starting at the signing of the informed consent and up to at least 6 months after completion of treatment or the last dose, whichever occurs first
14. Patients must not have undergone a major surgical procedure within 4 weeks prior to study treatment. The surgical wound should be completely healed

Exclusion Criteria:

1. Local pancreatic cancer (stage IA-IIB) or locally advance cancer (stage III), following the TNM 7th edition classification. Patients with metastatic disease that relapse after the initial diagnosis of local or advance disease could be included in this study
2. Pancreatic endocrine tumor and ampulloma
3. Evidence of carcinomatosis meningitis or brain metastasis. In case of clinical suspicious of brain metastasis is mandatory to perform a brain TAC/MR 4 weeks prior de inclusion.
4. Primary tumors developed 5 years previous to the inclusion, except in situ cervix carcinoma or skin basocellular cancer properly treated
5. Cardiovascular disease clinically significant (active):

   * Non-controlled arterial hypertension (Systolic pressure \> 150 mg Hg and/or diastolic pressure \> 100 mm Hg on repeated pressure measurements)
   * Cerebrovascular accident/ictus (≤ 6 weeks prior to inclusion)
   * Myocardial infarction (≤ 6 months prior to inclusion)
   * Unstable angina
   * Congestive cardiac insufficiency (grade II or superior following to New York Heart Association (NYHA)
   * Severe cardiac arrythmia requiring treatment
6. Significant ophthalmologic anomalies
7. Deficit in Dihydropyrimidine-Dehydrogenase (DPD)
8. Unable to take oral drug. Previous surgical process that affect the absorption or make the needed to have intravenous feeding or parenteral nutrition with lipids
9. Pregnancy women or in lactation period
10. Antineoplastic treatment (chemotherapy, hormonal treatment, radiotherapy, surgery, biological therapy or tumor embolization) 4 weeks prior the inclusion
11. Previous treatment with capecitabine or EGFR inhibitor
12. Metabolic disease or any other disease which, in the investigator's opinion, might interfere with the treatment in study
13. Known hypersensibility to any study drug (gemcitabine, erlotinib, capecitabine) or to 5-fluorouracile and fluoropyrimidines
14. Current infection grade ≥ 2 (CTCAE)
15. Known human immunodeficiency virus infection, or chronic infection with hepatitis B or C virus, or severe uncontrolled intercurrent infection or other severe uncontrolled concomitant diseases
16. Medical, psychological, psychiatric or sociological conditions that would interfere to the patient participation in the study or in the assessment of the results
17. Current or 30 days previous to study treatment with other investigational drug or participation in other trial
C: Inclusion Criteria:

* adult patients, \>=18 years of age;
* histologically or cytologically documented locally advanced-unresectable or metastatic pancreatic cancer;
* measurable disease according to RECIST;
* failure of at least one prior chemotherapy regimen, or who are deemed unsuitable for chemotherapy;
* ECOG performance status of 0-2.

Exclusion Criteria:

* local or locally advanced-resectable pancreatic cancer;
* any other malignancies within last 5 years, except for adequately treated cancer in situ of the cervix, or basal or squamous cell skin cancer;
* major surgery within 2 weeks prior to randomization.
D: Inclusion Criteria:

* The patient has provided signed written informed consent.
* The patient is ≥18 years of age.
* The patient has histologically or cytologically-confirmed pancreatic adenocarcinoma not amenable to curative treatment with surgery or has documented or suspected extrapancreatic metastases.
* The patient has either (a) measurable disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST) or (b) non-measurable disease with an elevated baseline CA19-9 level (≥2 x the upper limit of normal \[ULN\]).
* The patient's Eastern Cooperative Oncology Group (ECOG) performance status is ≤2.
* The patient has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥1500/mm3 and a platelet count ≥100,000/mm3 obtained within 2 weeks prior to the first dose of study medication.
* The patient has adequate hepatic function as defined by a total bilirubin ≤2.0 mg/dL and transaminases ≤5.0 x ULN obtained within 2 weeks prior to the first dose of study medication.
* The patient has adequate renal function as defined by serum creatinine ≤2.0 x ULN and urine dipstick for proteinuria ≤1+ obtained within 2 weeks prior to the first dose of study medication. If urine dipstick is ≥2+, then a 24-hour urine for protein must demonstrate \< 1000 mg of protein in 24 hours to allow participation in the study. Urinalysis is also acceptable.
* If the patient is on full-dose anticoagulation therapy (eg, warfarin or low molecular weight \[LMW\] heparin), the following criteria must be met:

  * The patient has an in-range International Normalized Ratio (\[INR\]usually between 2 and 3) on a stable dose of oral anticoagulant or be on a stable dose of LMW heparin
  * The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
* If the patient is not on full-dose anticoagulation therapy, the following criteria must be met:

  * The patient has adequate coagulation function as defined by INR ≤1.5
  * The patient has a partial thromboplastin (PTT) ≤ULN obtained within 2 weeks prior to the first dose of study medication
* If a woman, the patient agrees to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study. If a male and sexually active, the patient agrees to use effective contraception.
* The patient is accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center.

Exclusion Criteria:

* Endocrine tumors or lymphoma of the pancreas
* Known brain metastases
* Prior therapy with an epidermal growth factor receptor (EGFR) inhibitor or vascular endothelial growth factor (VEGF) inhibitor
* Prior chemotherapy, hormonal therapy, or radiation therapy for advanced pancreatic cancer, patients who received chemotherapy and/or radiation therapy in the adjuvant setting will be eligible as long as the adjuvant therapy was completed \>6 months prior
* Concurrent malignancy other than non-melanomatous skin cancer or carcinoma in situ of the cervix
* Concurrent treatment with other anti-cancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy
* Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
* History of arterial thrombotic events within 9 months
* History of uncontrolled hypertension (\>150/100 mmHg) not on a stable regimen of anti-hypertensive therapy
* History of significant bleeding events or upper or lower gastrointestinal bleeding within 9 months
* History of gastrointestinal perforation within 12 months
* Serious non-healing wound ulcer, bone fracture, or major surgical procedure with 28 days
* If a woman, is pregnant or lactating
* An employee of the investigator or study center as well as family members of the employees

Answer: D