This study has several purposes. DCE-MRI will be used to image the tumor. Safety of cetuximab given before surgery will be studied. Cetuximab delivery to the tumor will be studied. In Stage 2 of this study, the safety of cetuximab and PEGPH20 given before surgery will be studied. Also, the effects of PEGPH20 on tumors will be studied.

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed PDAC. Pathologic confirmation is mandated before initiation of any protocol specified imaging studies or drug administrations. It is recognized that for some patients, histologic or cytologic confirmation of cancer may be obtained following study enrollment. Patient volunteers to the DW- and DCE-MRI sequence parameter optimization imaging portion of the study are eligible if they have any pancreatic lesion, histologic or cytologic confirmation of pathology is not required for this patient volunteer group.

• Radiographically resectable PDAC as adjudicated by MSKCC surgical oncologist without evidence of distant metastases by CT or by laparoscopy, if performed at the discretion of the surgeon.

• Age > 18 years.

• ECOG Performance Score of 0 - 2.

• Absolute neutrophil count > 1,500 cells/mm3

• Platelet count > 100,000 cells/mm3.

• Adequate renal function as evidenced by serum creatinine < 1.6 mg/dL.

  • INR < 1.5, unless patient is on therapeutic anticoagulation where a therapeutic INR is acceptable. Anticoagulation with low molecular weight heparin or warfarin, where medically indicated, is permitted.

• Patient volunteers for the DW- and DCE-MRI sequence parameter optimization portion of the study are exempt from criteria 2, 5, 6 and 8.

• Women of childbearing potential must have a negative pregnancy test prior to the administration of protocol specified interventions.

• Ability to understand informed consent and signing of written informed consent prior to initiation of protocol therapy.

Exclusion Criteria:

• Patients with histology other than adenocarcinoma, e.g., neuroendocrine cancer or acinar cancers, are ineligible.
• No prior therapy for pancreas cancer is allowed.
• Patients with metastatic or locally unresectable PDAC (resectability is as defined by MSKCC pancreatic surgeon and as outlined
• Active infection, with the exception of resolving cholangitis, will preclude enrollment on the study. Preoperative interventions can only be initiated when acute cholangitis has resolved.
• Patients with known hypersensitivity to any of the components of PEGPH20 or cetuximab.
• For patients who choose to undergo MRI imaging, hypersensitivity to MRI IV contrast media not suitable for pre-medication.
• Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication).
• Patients who have a history of venous or arterial thromboembolic events including pulmonary embolism, deep venous thrombosis and stroke.
• Patients who are pregnant or lactating
• For patients who choose to undergo MRI imaging patients who are ineligible for an MRI with contrast based on Radiology Department screening.
• Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or follow up procedures.
• Patient volunteers for the DW- and DCE-MRI sequence parameter optimization portion are exempt from criteria 12, 13, 14, 15, 16 and 18.