A Phase II, Randomized, Open-Label Study of Cetuximab and Bevacizumab Alone or in Combination With Fixed-Dose Rate Gemcitabine as First-Line Therapy of Patients With Metastatic Adenocarcinoma of the Pancreas
- 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
- 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
- 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
- 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
- The patient is accessible for treatment and follow-up. Patients enrolled in this
trial must be treated at the participating center.
- 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
- Concurrent malignancy other than non-melanomatous skin cancer or carcinoma in situ of
- 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
- 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
- If a woman, is pregnant or lactating
- An employee of the investigator or study center as well as family members of the