Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III Randomized Open-Label Study Comparing Gemcitabine Plus Cetuximab (IMC-C225) Versus Gemcitabine As First-Line Therapy Of Patients With Advanced Pancreas Cancer
Brief Summary: RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as cetuximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether gemcitabine is more effective with or without cetuximab in treating pancreatic cancer.

PURPOSE: This randomized phase III trial is studying giving gemcitabine together with cetuximab to see how well it works compared to giving gemcitabine alone as first-line therapy in treating patients with locally advanced unresectable or metastatic adenocarcinoma of the pancreas.


Options:
A: 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
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:

* metastatic chemotherapy-naïve pancreatic cancer patients
* histologically confirmed
* adequate samples for analysis
* Eastern Cooperative Oncology Group (ECOG) performance status \<= 2
* absolute neutrophil count (ANC) \>= 1,500/mm3
* platelet count \>= 100,000/mm3
* serum creatinine \<= 1.5 mg/dL
* aspartate aminotransferase (AST)
* alanine aminotransferase (ALT) \< 5 times the upper limit of normal

Exclusion Criteria:

* absence of any other malignancy or serious medical or psychological illness that would preclude informed consent
D: DISEASE CHARACTERISTICS:

* Histologically\* or cytologically confirmed pancreatic adenocarcinoma meeting 1 of the following criteria:

  * Locally advanced unresectable disease
  * Distant metastatic disease NOTE: If diagnosis is based on a metastatic site the histology must be compatible with pancreatic cancer
* Measurable or nonmeasurable disease by x-ray, scan, or physical examination
* Tumor tissue must be submitted for evaluation of epidermal growth factor receptor expression before study entry
* None of the following tumor types are allowed:

  * Endocrine tumors
  * Lymphoma of the pancreas
  * Ampullary cancer
* No known brain metastases

PATIENT CHARACTERISTICS:

Age

* Not specified

Performance status

* Zubrod 0-2

Life expectancy

* At least 3 months

Hematopoietic

* Absolute granulocyte count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic

* Bilirubin no greater than 2.0 times upper limit of normal (ULN)
* SGOT or SGPT no greater than 2.5 times ULN

Renal

* Creatinine no greater than 2.0 mg/dL

Cardiovascular

* No significant history of cardiac disease
* No uncontrolled hypertension
* No unstable angina
* No uncontrolled arrhythmia
* No congestive heart failure

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* HIV negative
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is currently in remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior immunotherapy for advanced pancreatic cancer
* No prior cetuximab or other therapy that targets the epidermal growth factor pathway
* No prior chimerized or murine monoclonal antibody therapy
* No other concurrent anticancer immunotherapy

Chemotherapy

* At least 6 months since prior adjuvant chemotherapy
* No prior chemotherapy or chemoradiotherapy for advanced pancreatic cancer
* No prior gemcitabine
* No other concurrent anticancer chemotherapy

Endocrine therapy

* No prior hormonal therapy for advanced pancreatic cancer
* No concurrent anticancer hormonal therapy

Radiotherapy

* See Chemotherapy
* At least 28 days since prior radiotherapy and recovered
* Prior palliative radiotherapy to metastatic sites allowed
* No concurrent anticancer radiotherapy, including whole brain radiotherapy for progressive disease (i.e., CNS metastasis)

Surgery

* At least 14 days since prior pancreatic cancer surgery and recovered

Other

* No other concurrent anticancer therapy

Answer: D