Cetuximab, Gemcitabine, and Oxaliplatin Followed By Surgery or External-Beam Radiation Therapy and Capecitabine in Treating Patients With Locally Advanced, Nonmetastatic Pancreatic Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as gemcitabine, oxaliplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving cetuximab together with chemotherapy may reduce drug resistance and allow the tumor cells to be killed. Giving cetuximab and chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells. PURPOSE: This phase II trial is studying how well giving cetuximab together with oxaliplatin and gemcitabine followed by surgery or external-beam radiation therapy and capecitabine works in treating patients with locally advanced, nonmetastatic pancreatic cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the progression-free survival rate in patients with unresectable, locally advanced, nonmetastatic adenocarcinoma of the pancreas treated with neoadjuvant therapy comprising cetuximab, gemcitabine hydrochloride, and oxaliplatin followed by either surgery or chemoradiotherapy comprising external-beam radiotherapy and capecitabine. Secondary Determine the toxicity and tolerability of this regimen in these patients. Determine overall survival and progression-free survival. Determine the response rate in these patients. Determine the response duration (defined as the time from first observation response to the time of progressive disease) in patients who achieve at least a partial response to treatment. Determine the biomarker response of CA19-9. OUTLINE: This is an open-label study. Neoadjuvant therapy: Patients receive cetuximab IV over 1-2 hours on days 1 and 8, gemcitabine hydrochloride IV over 100 minutes on day 1, and oxaliplatin IV over 2 hours on day 2. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients are evaluated after completion of neoadjuvant therapy. Patients with metastatic disease are taken off study. Beginning within 4 weeks after completion of neoadjuvant therapy, patients with resectable disease proceed to surgical resection or chemoradiotherapy (by choice); patients with unresectable disease proceed to chemoradiotherapy. Surgery: Patients undergo surgical resection with the Whipple procedure. Chemoradiotherapy: Patients receive oral capecitabine twice daily 5 days a week (on days 1-5) and undergo external-beam radiotherapy once daily 5 days a week for 5½ weeks. After completion of study treatment, patients are followed every 3 months for 1 year. PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Official Title
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Phase II Study of Neoadjuvant Gemcitabine/Oxaliplatin and Cetuximab Followed by Surgery or Concurrent External Beam Radiation With Capecitabine for Patients With Locally Advanced Unresectable Nonmetastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: capecitabine
* Drug: oxaliplatin
* Procedure: conventional surgery
* Radiation: radiation therapy
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or radiologically confirmed pancreatic cancer, meeting both of the following criteria: Locally advanced, nonmetastatic disease Surgically unresectable disease Measurable disease, defined as unidimensionally measurable by physical exam or imaging study The following are considered nonmeasurable disease: Bone-only disease Pleural or peritoneal effusions CNS lesions Irradiated lesions in the absence of progression after radiotherapy No history or evidence of CNS disease No metastatic disease to distant organs (e.g., liver, lung, brain, or bone) PATIENT CHARACTERISTICS: ECOG performance status 0-2 Granulocyte count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Bilirubin ≤ 2.0 mg/dL Creatinine ≤ 2.0 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for ≥ 90 days after completion of study therapy No acute hepatitis No known HIV positivity No active or uncontrolled infection No significant history of uncontrolled cardiac disease, including, but not limited to, any of the following: Uncontrolled hypertension Unstable angina Myocardial infarction within the past 6 months Uncontrolled congestive heart failure Cardiomyopathy with decreased ejection fraction No prior severe infusion reaction to a monoclonal antibody No active second malignancy other than nonmelanoma skin cancer No history of deep vein thrombosis No history of bleeding diathesis or coagulopathy No other severe concurrent disease, mental incapacitation, or psychiatric illness that would preclude study participation PRIOR CONCURRENT THERAPY: No prior therapy for pancreatic cancer No prior therapy specifically targeting the epidermal growth factor-receptor pathway No major surgical procedure or open biopsy within the past 28 days No prior radiotherapy or chemotherapy No prior or concurrent full-dose anticoagulants or thrombolytics

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gemcitabine,Oxaliplatin and Cetuximab<br>Gemcitabine will be given on day 1 of every 2 week cycle. Oxaliplatin will be given day 2 of every 2 week cycle. Cetuximab will be given every week for 12 weeks. After chemotherapy, patient will be assessed for resectability. Patients will have either surgery or daily radiation and capceitabine Monday-Friday for a total of 5 and a half weeks. | Biological: cetuximab<br> <br> Drug: capecitabine<br> <br> Drug: oxaliplatin<br> <br> Procedure: conventional surgery<br> <br> Radiation: radiation therapy<br> <br> Drug: Gemcitabine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival at 6 Months |  | up to 46 weeks after the start of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Grade 3-4 Adverse Events Reported |  | from start of study treatment until end of study visit, about 30 weeks | 
| Overall Survival |  | up to 46 weeks after the start of study treatment | 
| Response Rate | defined as the total number of subjects whose best response is PR or CR. | up to 46 weeks after the start of study treatment | 
| Response Duration in Patients With at Least Partial Response to Treatment |  | up to 46 weeks after the start of study treatment | 
| Determine the Biomarker Response of CA 19-9 to Therapy |  | from start up treatment to one year after end of treatment, up to 81 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the pancreas, stage II pancreatic cancer, stage III pancreatic cancer