Induction Cetuximab (IM-C225), Gemcitabine, and Oxaliplatin in Pancreatic Cancer Patients
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Cetuximab; Gemcitabine; Oxaliplatin; Capecitabine; Radiotherapy
Intervention description: 500 mg/m^2 IV/week +/-1 day continued throughout induction chemotherapy, chemoradiation and maintenance chemotherapy.; Induction Therapy: 1 gm/m^2 over 100 minutes every 2 weeks +/-1 day for 4 doses.
Chemotherapy Maintenance: 1 gm/m^2/week over 100 minutes weekly for 3 weeks then 1 week off.; Induction Chemotherapy: 100 mg/m^2 over 120 minutes every 2 weeks +/-1 day for 4 doses.; Chemoradiation (to start 2-3 weeks post completion of oxaliplatin and gemcitabine): 825 mg/m^2 by mouth (PO) twice daily Monday-Friday throughout radiation.; Conformal radiation therapy to gross disease, total dose = 50.4 Gy delivered in 28 fractions.
Intervention MeSH terms: Gemcitabine; Capecitabine; Oxaliplatin; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pancreatic Cancer; Cetuximab; C225; Erbitux; Gemcitabine; Oxaliplatin; Eloxatin; Capecitabine; Xeloda

Summary:

      The primary objective is to evaluate the efficacy of a combination of cetuximab with systemic
      chemotherapy followed by chemoradiation in locally advanced pancreatic cancer. The primary
      endpoint is actuarial one-year survival.

      The secondary objectives are:

        -  To evaluate the local tumor response in patients treated with the above regimen.

        -  To characterize the safety of the above regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Cytologic or histologic proof of adenocarcinoma of the pancreas is required prior to
             treatment. Patients can have tumor originating in any part of the pancreas. Islet cell
             tumors are not eligible. Only patients with non- metastatic, unresectable disease
             (AJCC 2002 stage T4 NX M0) are eligible. Computed Tomography (CT) findings of lung,
             liver, peritoneal metastasis are equivocal, are eligible. Patients who cannot undergo
             resection because of underlying medical problems are also eligible. Diagnosis of
             Pancreatic Adenocarcinoma by bile duce brushings are acceptable. Patients with
             regional nodal disease are eligible.

          2. All patients must be staged with a physical exam, chest X-ray (CXR), and
             contrast-enhanced helical thin-cut abdominal CT. Unresectability is defined by CT
             criteria: a) evidence of tumor extension to the celiac axis or superior mesenteric
             (SM) artery, or b) evidence on either CT or angiogram of occlusion of the SM vein or
             SM/ portal vein confluence. If a tumor does not meet this definition and is found to
             be unresectable at surgical exploration, then that tumor is considered unresectable.

          3. Patients must be 18 years and older. There will be no upper age restriction

          4. Karnofsky performance status greater than or equal to 70 are eligible.

          5. Patients must either be not of child bearing potential or have a negative urine
             pregnancy test within 72 hours of treatment. Patients are considered not of child
             bearing potential if they are surgically sterile (they have undergone a hysterectomy,
             bilateral tubal ligation or bilateral oophorectomy) or they have been postmenopausal
             for at least 12 months.

          6. Women of childbearing potential must agree to practice adequate contraception and to
             refrain from breast-feeding, as specified in the informed consent. Sexually active
             males must practice contraception during the study.

          7. Bone marrow function: absolute neutrophil count (ANC) >1,500/ul. Platelets
             >100,000/ul.

          8. Renal function: creatinine clearance >30 mL/min (calculated with Cockcroft-Gault
             equation).

          9. Hepatic function: Total bilirubin less than 5mg/dL. If the patient required an
             endobiliary stent, the bilirubin level must have declined on consecutive measurements
             indicating adequate biliary decompression; alanine aminotransferase (ALT) less than or
             equal to 5 times the upper limit of normal.

         10. Neurologic function: neuropathy (sensory) < Common Toxicity Criteria (CTC) Grade 2.

         11. Patients must sign a study-specific consent form, which is attached to this protocol.

        Exclusion Criteria:

          1. Patients with a history of prior metastatic cancer.

          2. Patients must not have significant infection,i.e., requiring intravenous (IV)
             antibiotics, or other coexistent medical condition that would preclude protocol
             therapy.

          3. Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension,
             unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled
             congestive heart failure, and cardiomyopathy with ejection fraction less than <30%.

          4. Prior therapy which specifically and directly targets the estimated EGFR pathway.

          5. Prior severe infusion reaction (bronchospasm, stridor, urticaria and/or hypotension)
             to a monoclonal antibody.

          6. Any prior history of radiotherapy to the abdomen.

          7. History or evidence upon physical examination of central nervous system (CNS) disease
             (e.g., primary brain tumor, seizures not controlled with standard medical therapy, any
             brain metastases, or history of stroke)

          8. Prior unanticipated severe reaction to fluoropyrimidine therapy or known
             hypersensitivity to 5-fluorouracil.

          9. Patients who have had an organ allograft.

         10. Patients on Coumadin must be changed to Lovenox at least 1 week prior to starting
             capecitabine. Low dose (1 mg) Coumadin is allowed.

         11. Patients taking Sorivudine or Brivudine A must be off of these drugs for 4 weeks prior
             to starting capecitabine. Patients taking cimetidine must have this drug discontinued.
             Ranitidine or a drug from another anti-ulcer class can be substituted for cimetidine
             if necessary.