Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase IIb Randomized Study to Evaluate the Efficacy of Gemcitabine-erlotinib Versus Gemcitabine-erlotinib-capecitabine in Patients With Metastatic Pancreatic Cancer
Brief Summary: The purpose of the study is to evaluate the efficacy of the combination of gemcitabine-erlotinib versus gemcitabine-erlotinib-capecitabine in patients with metastatic pancreatic cancer.


Options:
A: 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
B: Inclusion Criteria:

* 18 years old or older
* Histologically or cytologically confirmed diagnosis of metastatic (Stage IV) adenocarcinoma of the pancreas with measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale
* All prior treatment related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) (Version 4.0) ≤ Grade 1 (except alopecia) at the time of randomization
* Adequate baseline organ function
* Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels

Exclusion Criteria:

* Prior systemic therapy (i.e., chemotherapy, immunotherapy, hormone therapy, , targeted therapy or any investigational anti-cancer drug) for metastatic pancreatic adenocarcinoma.

(Prior treatment with 5-FU based or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. Prior systemic chemotherapy in the adjuvant setting is allowed ; however, prior therapy with gemcitabine is allowed only if tumor recurrence occurred at least 6 months after completing the last dose of gemcitabine)

* History of another malignancy. Exception: Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled. Consult GSK Medical Monitor if unsure whether second malignancies meet requirements specified above
* Any serious and/or unstable pre-existing medical (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator or GSK Medical Monitor
* History of interstitial lung disease or pneumonitis
* History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
* Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression
* History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 6 months
C: Inclusion Criteria:

* Pathologically confirmed metastatic adenocarcinoma of the pancreas (AJCC Stage IV). Subjects with islet cell neoplasms are excluded
* Non-measurable or measurable disease based on the RECIST criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* Life expectancy of \> 3 months
* Hematologic function, as follows:

  * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  * Platelet count ≥ 100 x 109/L
  * Hemoglobin ≥ 9 g/dL (transfusion independent)
* Renal function, as follows:

  * Creatinine ≤ 2.0 mg/dL
* Hepatic function, as follows:

  * Aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤ 5 x ULN if known liver metastases.
  * Alanine aminotransferase (ALT) ≤ 2.5 x ULN or ≤ 5 x ULN if known liver metastases
  * Bilirubin ≤ 2 x ULN
* INR \< 1.3 (or ≤ 3 if on warfarin for therapeutic anti-coagulation)

Exclusion Criteria:

* Prior systemic therapy for metastatic pancreatic cancer

  * Subjects who have received adjuvant treatment with gemcitabine and who had relapse metastatically are allowed
  * Subjects with advanced local disease who have received treatment with gemcitabine and in whom progression has been observed with the onset of metastases less than 6 months are excluded
* Chemotherapy and/or radiation within 4 weeks of study enrollment
* Prior monoclonal antibody therapy within 60 days of study enrollment
* Known brain or leptomeningeal disease
* History of other primary malignancy, unless:

  * Curatively resected non-melanomatous skin cancer
  * Other malignancy curatively treated with no known active disease present and no treatment administered for the last 3 years
* Active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System)
* Use of any investigational product within 4 weeks of study enrollment
* Major surgery (that requires general anesthesia) within 4 weeks before study enrollment
* Women who are pregnant (confirmed by positive pregnancy test) or lactating
* Man or woman of childbearing potential not consenting to use adequate contraceptive precautions during the course of the study and for 4 weeks after the last AGS-1C4D4 and/or gemcitabine infusion administration
* Subject known to be human immunodeficiency, hepatitis B or hepatitis C virus positive
* Active serious infection not controlled with antibiotics
D: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed adenocarcinoma of the pancreas

  * No other pancreatic tumor type, including either of the following:

    * Neuroendocrine tumor
    * Ampulla of Vater carcinoma
  * Metastatic disease
* Measurable or evaluable disease
* Unresectable disease, defined as either of the following:

  * Failed prior attempt of surgical resection by laparotomy
  * Surgical resection contraindicated by radiographic criteria (e.g., arterial vascular invasion)
* No cerebral metastases

PATIENT CHARACTERISTICS:

Age

* 18 to 75

Performance status

* Karnofsky 70-100%

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3

Hepatic

* Bilirubin \< 1.5 times upper limit of normal
* No hepatic disturbance

Renal

* Creatinine \< 120 mmol/L

Cardiovascular

* No untreated cardiac or coronary insufficiency
* No uncontrolled symptomatic arrhythmia
* No uncontrolled angina

Pulmonary

* No uncontrolled respiratory insufficiency

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No other malignancy except basal cell skin cancer or carcinoma in situ of the cervix
* No peripheral neuropathy ≥ grade 2
* No ongoing active infection
* No other serious uncontrolled medical disorder that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* No prior radiotherapy to the celiac or pancreatic area

Surgery

* See Disease Characteristics

Answer: A