MK-0646 and Gemcitabine +/- Erlotinib for Patients With Advanced Pancreatic Cancer

Inclusion Criteria:

1. Pathologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma, AJCC stage IV
2. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as =/\>20 mm with conventional techniques or as =/\>10 mm with spiral CT scan. See Section 11 for the evaluation of measurable disease. Measurable disease must be present outside a previous radiation field or if inside, it must be a new lesion.
3. At least 6 months must have elapsed after completion of adjuvant therapy (if applicable).
4. Age =/\>18 years.
5. ECOG Performance Status 0-1 (Karnofsky =/\>60%).
6. Patients must have adequate organ and marrow function as defined below: 1) leukocytes =/\>3,000 cells/mm\^3; 2) absolute neutrophil count =/\>1,500 cells/mm\^3; 4) platelets =/\>100,000 cells/mm\^3; 5) total bilirubin \<1.5mg/dl; 6) AST(SGOT)/ALT(SGPT) =/\<2.5 X institutional upper limit of normal for patients without liver metastasis, =/\< 5X institutional upper limit of normal for patients with liver metastasis; 7) creatinine - within normal institutional limits OR creatinine clearance =/\>60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
7. Fasting blood glucose =/\<160 mg/dl, prior to study enrollment. (For higher values, blood glucose may be controlled by dietary intervention, oral hypoglycemics and/ or insulin prior to enrollment).
8. Women of child-bearing potential (defined as not post-menopausal for 12 months or no previous surgical sterilization) and fertile men must agree to use adequate contraception for the duration of study participation. Acceptable contraception is defined as double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Acceptable contraception must be used for 90 days after last dose of study drugs.
9. (Continuation of inclusion criteria # 8) Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
10. Ability to understand and the willingness to sign a written informed consent document. Signed informed consent form must be obtained prior to initiation of study evaluations and/or activities.
11. INR \<1.5 (or =/\<3 if on anticoagulation therapy)
12. Both men and women and members of all races and ethnic groups are eligible for this trial.
13. In phase II expansion cohort, which is primarily for predictive biomarker correlation, patients enrolled will be those with pre-existing core biopsies of primary tumor or metastatic site or must be willing to undergo a biopsy for correlative studies.

Exclusion Criteria:

1. Prior systemic chemotherapy or biological therapy for metastatic disease
2. Prior exposure to IGF-1R inhibitors.
3. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
6. Pregnant or nursing women are excluded from this study because there is an unknown but potential risk for adverse events in infants secondary to treatment of the mother the study agents. If a pregnancy test (serum or urine) is positive, patient will be excluded.
7. Patients who are known to be HIV-positive are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
8. No other prior malignancy is allowed except for the following: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or any other cancer from which the patient has been disease-free for two years.
9. Patients must not be currently enrolled in a therapeutic study for pancreatic cancer.