Preoperative Chemoradiotherapy With Gemcitabine for Resectable Pancreatic Carcinoma

Study Overview
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Brief Summary
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This phase II study is to evaluate the efficacy of preoperative chemoradiotherapy with gemcitabine (400mg/m2, weekly) for resectable pancreatic cancer.

Detailed Description
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The primary objective of this study is to evaluate the complete (R0) resection rate for patients with and resectable pancreatic cancer treated with preoperative chemoradiotherapy and curative surgery. An experimental arm that result a complete resection rate of at least 90% would merit further study. With 90% power to reject that null hypothesis that the true complete resection rate is ≤75% with a type I error level of 5%, evaluable 53 patients are required. Considering the 20% unevaluable patients due to the immediate distant metastasis after treatment7, 8, 17 and 10% follow up loss, a total of 64 eligible patients will be enrolled.

Official Title
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A Phase 2 Study of Preoperative Chemoradiotherapy With Gemcitabine for Resectable Pancreatic Carcinoma

Conditions
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Resectable Pancreatic Carcinoma

Intervention / Treatment
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* Radiation: chemoradiotherapy with Gemcitabine
* Radiation: Radiation: chemoradiotherapy with Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with resectable pancreatic adenocarcinoma Age over 18 years old and younger than 70 year old Performance status (ECOG scale): 0-1 Adequate organ functions Hb ≥9.0 g/dl ANC ≥1,500/mm3 PLT ≥100,000/mm3 Liver function: Total Bilirubin ≤3.0 mg/dl AST/ALT/ALP ≤3× upper limit of normal Creatinine ≤1.5 ULN Patients should sign a written informed consent before study entry. Exclusion Criteria: Tumor type other than adenocarcinoma Unresectable for resection on preoperative evaluation Other primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin or prior malignancy treated more than 5 years ago without recurrence) Prior systemic therapy (for instance, cytotoxic chemotherapy or active/passive immunotherapy) Prior radiotherapy Major surgery within 4 weeks prior to study treatment Serious illness or medical conditions, as follows; congestive heart failure (NYHA class III or IV) unstable angina or myocardial infarction within the past 6 months, significant arrhythmias requiring medication and conduction abnormality such as over 2nd degree AV block uncontrolled hypertension hepatic cirrhosis( ≥ Child class B) interstitial pneumonia, pulmonary adenomatosis psychiatric disorder that may interfere with and/or protocol compliance unstable diabetes mellitus uncontrolled ascites or pleural effusion active infection Received any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment with study drug Pregnant or lactating woman Women of child bearing potential not using a contraceptive method Sexually active fertile men not using effective birth control during medication of study drug and up to 6 months after completion of study drug if their partners are women of child-bearing potential Any patients judged by the investigator to be unfit to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Radiation: chemoradiotherapy with Gemcitabine<br>Radiation: chemoradiotherapy with Gemcitabine All patients will receive gemcitabine 400 mg/m2 as an intravenous 30-min infusion on day 1, 8, 15, 22, and 29 with radiotherapy.After 4-6 week from end date of chemoradiotherapy, patients undergo preoperative evaluation including CT, PET, CA19-9, CEA. If the patient is feasible for resection on this evaluation, the surgery is performed in 1 to 2 weeks. After surgery, patients will receive gemcitabine 1000 mg/m2 as an intravenous 30-min infusion on day 1, 8, and 15 for every 28 days. Subjects will be treated for at least 1 cycle and to a maximum of four cycles of adjuvant chemotherapy unless there is documented relapse, unacceptable adverse events or withdrawal of consent. | Radiation: chemoradiotherapy with Gemcitabine<br>* All patients will receive gemcitabine 400 mg/m2 as an intravenous 30-min infusion on day 1, 8, 15, 22, and 29 with radiotherapy.After 4-6 week from end date of chemoradiotherapy, patients undergo preoperative evaluation including CT, PET, CA19-9, CEA. If the patient is feasible for resection on this evaluation, the surgery is performed in 1 to 2 weeks. After surgery, patients will receive gemcitabine 1000 mg/m2 as an intravenous 30-min infusion on day 1, 8, and 15 for every 28 days. Subjects will be treated for at least 1 cycle and to a maximum of four cycles of adjuvant chemotherapy unless there is documented relapse, unacceptable adverse events or withdrawal of consent.<br>Radiation: Radiation: chemoradiotherapy with Gemcitabine<br>* Radiation: chemoradiotherapy with Gemcitabine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete resection rate | To evaluate the impact of preoperative chemoradiotherapy with gemcitabine by analyzing complete resection rate (R0). | Within the first 30 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical outcomes | To investigate the association between radiologic, histopathologic response, complete resection rate of preoperative chemoradiotherapy with gemcitabine and clinical outcomes, such overall survival and disease-free survival. | Up to 3years from a initial follow-up | 
| The association between biomolecular markers and clinical outcomes | To investigate the association between biomolecular markers and clinical outcomes (including tumor response and complete resection rate, etc.) | Up to 3years until study closed | 
| The feasibility and compliance | To evaluate the feasibility and compliance (acute and late toxicity, esp. gastrointestinal tract toxicity) of preoperative chemoradiotherapy with gemcitabine for resectable pancreatic cancer. | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preoperative chemoradiotherapy with Gemcitabine