Panitumumab, Chemotherapy, and External-Beam Radiation Therapy in Treating Patients With Locally Advanced 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 panitumumab, 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 fluorouracil, capecitabine, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. External-beam radiation therapy uses high-energy x-rays to kill tumor cells. Panitumumab may also stop the growth of pancreatic cancer by blocking blood flow to the tumor and make tumor cells more sensitive to radiation therapy. Giving panitumumab together with chemotherapy and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving panitumumab together with chemotherapy and external-beam radiation therapy works in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary To evaluate the 1-year survival rate in patients with locally advanced pancreatic cancer treated with panitumumab and continuous infusion fluorouracil administered concurrently with external-beam radiotherapy followed by gemcitabine and panitumumab. Secondary To determine overall survival, time to disease progression, confirmed response rate, duration of response, and time to treatment failure in patients treated with this regimen. To determine adverse events in patients treated with this regimen. OUTLINE: Panitumumab and chemoradiotherapy : Patients undergo external-beam radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38. Patients also receive panitumumab IV over 1 hour on days 1, 15, and 29 and fluorouracil IV continuously over 24 hours daily OR oral capecitabine twice daily beginning on day 1 and continuing through the last day of radiotherapy. Panitumumab and chemotherapy: Beginning 4-6 weeks after completion of panitumumab and chemoradiotherapy, patients receive panitumumab IV over 1 hour on days 1 and 15 and gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 3 courses. Patients then proceed to maintenance therapy. Maintenance therapy: Patients receive panitumumab IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

Official Title
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Phase II Study of Panitumumab, Chemotherapy, and External Beam Radiation in Patients With Locally Advanced Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: panitumumab
* Drug: capecitabine
* Drug: fluorouracil
* Drug: gemcitabine hydrochloride
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed unresectable adenocarcinoma of the pancreas Including subtotal resection and gross residual disease No microscopic residual disease only Measurable disease is not required Disease is encompassable within standard radiotherapy fields for pancreatic cancer No evidence of metastatic disease outside of the planned radiotherapy field No cystadenocarcinoma of the pancreas or pancreatic tumors of neuroendocrine origin No distant metastases (i.e., liver or lung metastases or peritoneal spread) No history or known presence of CNS metastases PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-1 ANC ≥ 1,500/mm³ Hemoglobin ≥ 9.0 g/dL Platelet count ≥ 100,000/mm³ Total bilirubin ≤ 3 times upper limit of normal (ULN)* NOTE: *Biliary stent placement or surgical bypass should be considered prior to treatment if impending bile duct obstruction by tumor AST ≤ 3 times ULN Creatinine ≤ 2.0 times ULN Magnesium normal Willing to return to an North Central Cancer Treatment Group (NCCTG) institution for follow-up Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 6 months after treatment with panitumumab No prior or concurrent malignancy unless disease-free ≥ 3 years except for non-melanoma skin cancer, carcinoma in situ of the cervix, or organ confined prostate cancer with Gleason score < 7 No nausea or vomiting > grade 1 No uncontrolled intercurrent illness including, but not limited to, any the following: Ongoing or active infection Psychiatric illness or social situations that would limit compliance with study requirements No New York Heart Association clinically significant cardiovascular disease ≥ grade 2, including any of the following within the past year: Myocardial infarction Unstable angina Symptomatic congestive heart failure Serious, uncontrolled cardiac arrhythmia No known HIV positivity No known hepatitis C virus or acute or chronic active hepatitis B infection Adequate oral nutrition PRIOR CONCURRENT THERAPY: More than 21 days since prior laparotomy No prior anti-epidermal growth factor receptor (EGFR) antibody therapy (e.g., cetuximab) No prior small molecule EGFR inhibitors (e.g., gefitinib, erlotinib, or lapatinib) No prior radiotherapy that would overlap with planned radiotherapy fields No prior or other concurrent chemotherapy No prior or other concurrent biologic therapy More than 4 weeks since prior and no concurrent or planned participation in another experimental drug study except studies with specific interventions intended to treat rashes associated with EGFR agents (e.g., N05C4) No concurrent enteral hyperalimentation No concurrent chronic immunosuppressive agents (e.g., methotrexate, cyclosporine, or corticosteroids) No concurrent colony-stimulating factors during the first course of therapy No other concurrent immunotherapy or radiotherapy

Ages Eligible for Study
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Minimum Age: 18 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: Panitumumab<br>Chemotherapy concurrent with radiation: Radiation 5 days per week for 5½ weeks; Panitumumab on days 1, 15, and 29 of radiation therapy 5-fluorouracil (5FU) continuous infusion, starting on day 1 and through last day of radiation. 4-6 weeks after completion of radiation therapy: Gemcitabine on days 1, 8, and 15 of each cycle, for 3 cycles; Panitumumab on days 1 and 15 of each cycle, for 3 cycles. Maintenance therapy: Panitumumab on days 1 and 15 of each cycle, for 6 cycles. | Biological: panitumumab<br> <br> Drug: capecitabine<br> <br> Drug: fluorouracil<br> <br> Drug: gemcitabine hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One Year Survival Rate | The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the exact binomial method. | Baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier | baseline to 2 years | 
| Progression Free Survival (PFS) | Progression Free Survival is defined as the time from registration to the earliest documented evidence of disease progression. | baseline to 2 years | 
| Confirmed Response Rate | A confirmed tumor response is defined to be a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 4 weeks apart according to the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. A complete response is defined as the disappearance of all target and non-target lesions. A partial response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of the target lesion from baseline. Confirmed tumor response will be evaluated using the first 6 cycles of treatment. | baseline to 2 years | 
| Duration of Response | Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented. | baseline to 2 years | 
| Time to Treatment Failure | Time to treatment failure is defined to be the time from the date of registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. The distribution of survival time will be estimated using the method of Kaplan-Meier. | baseline to 2 years | 

 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