Gemcitabine, Capecitabine, and 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: Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy that uses a 3-dimensional image of the tumor to help focus thin beams of radiation directly on the tumor, and giving radiation therapy in higher doses over a shorter period of time, may kill more tumor cells and have fewer side effects. It is not yet known which regimen of chemotherapy given together with radiation therapy is more effective in treating pancreatic cancer. PURPOSE: This randomized phase II trial is comparing the side effects of two regimens of gemcitabine and capecitabine given together with radiation therapy and to see how well they work in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: To evaluate the activity, safety, and feasibility of induction chemotherapy comprising gemcitabine and capecitabine followed by two different schedules of chemoradiotherapy comprising gemcitabine or capecitabine and radiotherapy in patients with locally advanced, nonmetastatic, unresectable pancreatic cancer. To determine which of the two experimental arms gives the highest generic and disease-specific aspects of health-related quality of life (HRQL) following treatment. To determine how HRQL varies during treatment and follow up in both arms. OUTLINE: This is a multicenter study. All patients receive a first induction therapy comprising gemcitabine IV on days 1, 8, and 15 and oral capecitabine twice daily on days 1-21. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Following the first induction therapy, patients with a WHO performance status of 0-1 who are responding or have stable disease that can be encompassed within a radically treatable radiotherapy volume are randomized to 1 of 2 treatment arms. Arm I: Second induction therapy (weeks 13-16): Patients receive gemcitabine IV once daily on days 1, 8, and 15 and oral capecitabine twice daily on days 1-21. Chemoradiotherapy (weeks 17-22): Patients receive gemcitabine IV once weekly on day 1 and undergo conformal radiotherapy 5 days a week for 5.5 weeks. Arm II: Second induction therapy (weeks 13-16): Patients receive gemcitabine IV once daily on days 1, 8, and 15 and oral capecitabine twice daily on days 1-21. Chemoradiotherapy (weeks 17-22): Patients receive oral capecitabine twice daily on days 1-5 and undergo conformal radiotherapy 5 days a week for 5.5 weeks. Patients complete quality-of-life questionnaires QLQ-C30 and PAN26 at baseline and at 17, 23, 26, 39, and 52 weeks. After completion of study treatment, patients are followed every 3 months.

Official Title
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A Multi-Center Randomized Phase II Study of Induction Chemotherapy Followed by Gemcitabine or Capecitabine Based Chemoradiotherapy for Locally Advanced Non-Metastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: gemcitabine hydrochloride
* Procedure: quality-of-life assessment
* Radiation: 3-dimensional conformal radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the pancreas Locally advanced, nonmetastatic, inoperable, or operable (but medically unfit for surgery) disease Palliative bypass procedure allowed Common bile duct stenting allowed Primary pancreatic lesion ≤ 7 cm in diameter as measured by CT scan of the thorax and abdomen within 4 weeks prior to registration No recurrent cancer following definitive pancreatic surgery PATIENT CHARACTERISTICS: WHO performance status (PS) 0-2 Neutrophil count ≥ 1.5 x 10^9/L Platelet count ≥ 100 x 10^9/L Hemoglobin ≥ 10 g/dL Serum bilirubin < 35 μmol/L (50 μmol/L allowed for patients who have had a recent biliary drain and whose bilirubin is descending) AST/ALT ≤ 2.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 5 times ULN GFR > 50 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 12 weeks after completion of study therapy No evidence of severe uncontrolled systemic diseases including uncontrolled coronary artery disease No myocardial infarction or stroke within the past 6 months No prior malignancies within the past 5 years except for carcinoma in situ of the cervix, adequately treated basal cell skin carcinoma, or any early-stage malignancy No suspected DPD deficiency No renal abnormalities (e.g., adult polycystic kidney disease, hydronephrosis, or ipsilateral single kidney) Must meet the following additional criteria for randomization: WHO PS 0-1 Loss of weight no greater than 10% of that at baseline PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 4 weeks since prior and no concurrent sorivudine or analogues No prior radiotherapy to the upper abdomen No concurrent methotrexate No concurrent allopurinol

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gemcitabine<br>GEMCAP induction chemotherapy (28 day cycle of IV gemcitabine 1000mg/m2 day 1, 8,15 and capecitabine 830mg/m2 bd for 21 days po) followed by gemcitabine 300mg/m2 weekly (IV) + 50.4Gy radiation over five and half weeks (1.8Gy per fraction, Monday-Friday) | Drug: capecitabine<br> <br> Drug: gemcitabine hydrochloride<br> <br> Procedure: quality-of-life assessment<br> <br> Radiation: 3-dimensional conformal radiation therapy<br> <br> |
| Active Comparator: chemoradiotherpay with capecitabine<br>GEMCAP induction chemotherapy (28 day cycle of IV gemcitabine 1000mg/m2 day 1, 8,15 and capecitabine 830mg/m2 bd for 21 days po), followed by capecitabine 830mg/m2 bd (po, Mon-Fri) + 50.4Gy radiation over five and half weeks (1.8Gy per fraction, Monday-Friday) | Drug: capecitabine<br> <br> Drug: gemcitabine hydrochloride<br> <br> Procedure: quality-of-life assessment<br> <br> Radiation: 3-dimensional conformal radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival at 39 weeks (from registration) according to RECIST criteria |  | Assessed 39 weeks from registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity according to NCI CTCAE v.3.0 |  | Assessed throughout trial treatment and follow-up | 
| Quality of life as measured by questionnaires QLQ-C30 and PAN26 at baseline and at 17, 23, 26, 39, and 52 weeks |  | Assessed throughout trial treatment and follow-up | 
| Overall survival at 52 weeks and time from registration to death by any cause |  | Assessed 52 weeks post registration and during NHS flagging | 
| Objective disease response according to RECIST criteria |  | 39 weeks post registration | 
| Progression-free survival (time to event) according to RECIST criteria |  | Assessed during NHS flagging at the end of the trial | 
| Radiotherapy quality assurance (adherence to protocol) |  | Upon completion of the trial | 

 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