A Phase I and Randomized Phase II Trial of Gemcitabine + Erlotinib (NSC-718781) + IMC-A12 (NSC-742460) vs. Gemcitabine + Erlotinib as First-Line Treatment in Patients With Metastatic Pancreatic Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed pancreatic adenocarcinoma

- Stage IV disease (any T, any N, M1 [distant metastases])

- Unresectable disease

- Histologic diagnosis based on a metastatic site must be compatible with
pancreatic cancer

- Measurable and/or nonmeasurable disease

- No endocrine or neuroendocrine tumors, lymphoma of the pancreas, or ampullary cancer

- No macroscopic residual disease post-resection as the only site of disease

- No clinically significant ascites

- No known brain metastases

- Patients with neurologic signs or symptoms must undergo brain imaging studies
AND studies must be negative for disease

- Zubrod performance status 0-1

- ANC ≥ 1,500/mcL

- Platelet count ≥ 100,000/mcL

- Hemoglobin ≥ 9 g/dL

- Leukocytes ≥ 3,000/mcL

- Total bilirubin normal

- SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN)

- Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

- Fasting serum glucose < 120 mg/dL or below the ULN

- Patients with diabetes mellitus who meet this criterion must be on a stable
dietary or therapeutic regimen for this condition

- INR ≤ 1.5 and PTT ≤ 5 seconds above ULN

- Not pregnant or nursing

- Fertile patients must use effective contraception

- Willing to submit previously collected tumor tissue specimens

- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to anti-IGF-1R recombinant monoclonal antibody IMC-A12

- No active acute or chronic infections requiring antibiotics

- No significant ongoing cardiac problems, including any of the following:

- Myocardial infarction within the past 6 months

- Uncontrolled hypertension

- Unstable angina

- Uncontrolled arrhythmia

- Congestive heart failure

- No known HIV infection

- No other prior malignancy, except for the following:

- Adequately treated basal cell or squamous cell skin cancer

- Carcinoma in situ of the cervix

- Adequately treated stage I or II cancer from which the patient is currently in
complete remission

- Any other cancer from which the patient has been disease-free for 5 years

- At least 14 days since prior surgery

- At least 28 days since prior radiotherapy for palliation to metastatic sites

- Patient must have other untreated metastatic sites that would qualify them for
this protocol

- At least 6 months since prior adjuvant chemotherapy

- No prior chemotherapy, hormonal therapy, immunotherapy, or chemoradiotherapy for
advanced or locally advanced pancreatic cancer, including drugs that target either
EGFR or IGFR

- No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy,
immunotherapy, or any other type of therapy for treatment of cancer

- No prior gemcitabine hydrochloride

- No prior chimerized or murine monoclonal antibody therapy

- No concurrent CYP3A4 inducers including, but not limited to, any of the following:

- Rifampicin

- Rifabutin

- Rifapentine

- Phenytoin

- Carbamazepine

- Phenobarbital

- Hypericum perforatum (St. John's wort)

- No concurrent CYP3A4 inhibitors including, but not limited to, any of the following:

- Atazanavir

- Clarithromycin

- Indinavir

- Itraconazole

- Ketoconazole

- Nefazodone

- Nelfinavir

- Ritonavir

- Saquinavir

- Telithromycin

- Troleandomycin

- Voriconazole

- Concurrent prophylactic low-dose coumadin or low molecular weight heparin allowed
provided coagulation criteria are met

- Full-dose anticoagulation allowed provided coagulation criteria are met and are under
strict control and monitoring