Bevacizumab and Gemcitabine Combined With Either Cetuximab or Erlotinib in Treating Patients With Advanced Pancreatic Cancer
Condition: Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: cetuximab; gemcitabine hydrochloride; bevacizumab; erlotinib hydrochloride
Intervention description: Given IV; Given IV; Given IV; Given orally
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Cetuximab; Gemcitabine; Erlotinib Hydrochloride; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 143.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial is studying bevacizumab, gemcitabine, and cetuximab to see how
      well they work compared to bevacizumab, gemcitabine, and erlotinib in treating patients with
      advanced pancreatic cancer. Monoclonal antibodies, such as cetuximab and bevacizumab, can
      locate tumor cells and either kill them or deliver tumor-killing substances to them without
      harming normal cells. Drugs used in chemotherapy, such as gemcitabine, work in different ways
      to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth
      of tumor cells by blocking the enzymes necessary for their growth. Combining bevacizumab and
      gemcitabine with either cetuximab or erlotinib may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the pancreas

               -  Advanced disease

                    -  Patients with locally advanced disease must have disease that extends
                       outside the boundaries of a standard radiation port

          -  Not amenable to curative surgery or radiotherapy

          -  Measurable disease

               -  At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques
                  OR ≥ 10 mm by spiral CT scan

               -  Pleural effusions and ascites are not considered measurable lesions

          -  No CNS disease, including primary brain tumors or brain metastasis

          -  No tumor invasion into the duodenum

          -  Performance status - ECOG 0-2

          -  More than 3 months

          -  Absolute neutrophil count ≥ 1,500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  WBC ≥ 3,000/mm^3

          -  No history of bleeding diatheses

          -  Bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  SGOT and SGPT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)

          -  INR ≤ 1.5 (≤ 3 for patients on warfarin)

          -  No esophageal varices

          -  Creatinine ≤ 1.5 mg/dL

          -  Creatinine clearance ≥ 60 mL/min

          -  Urine protein < 1+

          -  24-hour urine protein < 500 mg

          -  No history of a recent cerebrovascular accident

          -  No clinically significant cardiovascular disease

          -  No uncontrolled hypertension

          -  No New York Heart Association class II-IV congestive heart failure

          -  No serious cardiac arrhythmia requiring medication

          -  No peripheral vascular disease ≥ grade II

          -  None of the following arterial thromboembolic events within the past 6 months:

               -  Transient ischemic attack

               -  Cerebrovascular accident

               -  Unstable angina

               -  Myocardial infarction

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for at least 3 months
             after study participation

          -  HIV negative

          -  No significant traumatic injury within the past 28 days

          -  No gastrointestinal tract disease resulting in an inability to take oral medication

          -  No allergic reactions to compounds similar to bevacizumab, cetuximab, or erlotinib
             (e.g., Chinese hamster ovary cell products or recombinant humanized antibodies)

          -  No serious or non-healing wound, ulcer, or bone fracture

          -  No active infection requiring antibiotics

          -  No other active malignancy within the past 5 years except nonmelanoma skin cancer or
             carcinoma in situ of the cervix

          -  No prior bevacizumab or cetuximab

          -  No other prior vascular endothelial growth factor inhibitors

          -  No prior gemcitabine

          -  No prior cytotoxic chemotherapy for metastatic disease

          -  At least 4 weeks since prior adjuvant chemotherapy (6 weeks for mitomycin or
             nitrosoureas)

          -  At least 4 weeks since prior radiotherapy

               -  Must have a site of measurable disease outside the radiation port

          -  No prior surgical procedure affecting absorption

          -  More than 28 days since prior major surgical procedure or open biopsy

          -  More than 7 days since prior core biopsy

          -  No concurrent major surgical procedures

          -  No prior erlotinib

          -  No other prior epidermal growth factor receptor inhibitors

          -  At least 30 days since prior investigational drugs

          -  More than 1 month since prior thrombolytic agents

          -  Concurrent warfarin or low molecular weight heparin allowed provided the following
             criteria are met:

               -  Currently therapeutic on a stable dose

               -  INR target range ≤ 3

               -  Patients undergo weekly INR testing

               -  No evidence of active bleeding or pathological condition that carries high risk
                  of bleeding (e.g., tumor invading adjacent organs or esophageal varices)

          -  No concurrent chronic daily therapy with aspirin (> 325 mg/day) or nonsteroidal
             anti-inflammatory medications known to inhibit platelet function

          -  No other concurrent antiplatelet medications

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No other concurrent anticancer therapies or agents

          -  No other concurrent investigational drugs