Phase I Study of TS-1 With Concurrent Radiotherapy to Treat Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine whether combination of TS-1 and concurrent and short-course radiotherapy is feasible in metastatic pancreatic cancer. The rationale of this study primarily bases on the good efficacy of gemcitabine plus TS-1 and the great potential of local control of concurrent chemoradiotherapy in pancreatic cancer.

Official Title
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A Phase I Study of TS-1 With Concurrent Radiotherapy Followed by Gemcitabine and TS-1 in Metastatic Pancreatic Cancer (SR-GS Study)

Conditions
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Metastatic Pancreatic Cancer

Intervention / Treatment
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* Drug: S-1-CCRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically or cytologically proven, newly diagnosed pancreatic adenocarcinoma or adenosquamous carcinoma no previous radiotherapy, chemotherapy, targeted therapy, curative surgery, or immunotherapy used for pancreatic cancer presence of at least one measurable lesion, which must meet the criteria of being ≥ 20 mm in at least one dimension by conventional CT/MRI or ≥ 10 mm by spiral CT scan age between 20 and 79 years at registration ECOG PS of 0 or 1 adequate major organ functions ability to take the oral study medication (TS-1) no clinically significant abnormal ECG findings within 28 days (4 weeks) prior to registration voluntarily signed the written informed consent form Exclusion Criteria: pulmonary fibrosis or interstitial pneumonitis diagnosed within 28 days prior to registration presence of diarrhea ≥ CTCAE v.4.03 grade 2 concomitant active infection or significant co-morbid medical conditions moderate or severe ascites or pleural effusion that requires drainage central nervous system metastasis prior or concurrent malignancies within the last 3 years concomitant treatment with flucytosine, phenytoin or warfarin pregnant women or nursing mothers, or positive pregnancy test severe mental disorder judged ineligible by physician for participation in the study due to safety concern

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 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: S-1-CCRT<br>There are five dose levels and one arm only. Level 1: S-1, 25 mg/m2, bid, Day 1-14; RT 25 Gy/10 fx, Day 1-5, 8-12 Level 2: S-1, 25 mg/m2, bid, Day 1-14; RT 30 Gy/10 fx, Day 1-5, 8-12 Level 3: S-1, 30 mg/m2, bid, Day 1-14; RT 30 Gy/10 fx, Day 1-5, 8-12 Level 4: S-1, 30 mg/m2, bid, Day 1-16; RT 36 Gy/12 fx, Day 1-5, 8-12, 15-16 Level 5: S-1, 35 mg/m2, bid, Day 1-16; RT 36 Gy/12 fx, Day 1-5, 8-12, 15-16 All dose levels are followed by Gemcitabine/S-1 (G 1000 mg/m2, iv, D1 and 15 plus S-1 60/80/100 mg/day based on BSA, po, D1-7, D15-21, q4w) after the CCRT | Drug: S-1-CCRT<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum tolerated dose | Dose-limiting toxicities (DLT) are defined as the following manifestations of toxicity observed until completion of CCRT: grade 3 leucopenia and/or neutropenia with a fever ≥ 38°C lasting 3 days or more grade 3 leucopenia and/or neutropenia with infection grade 4 leucopenia and/or neutropenia lasting 3 days or more grade 4 leucopenia and/or neutropenia requiring G-CSF platelet < 25,000/mm3 , grade 3 thrombocytopenia requiring transfusion hemoglobin < 8.0 g/dL g. serum AST/ALT ≥ 10 times ULN h. total bilirubin ≥ 3 times ULN i. creatinine >3.0 - 6.0 times ULN (grade 3) i. grade 3 or 4 nonhematological toxicities including nausea, vomiting, anorexia, fatigue, constipation, hyperglycemia, and abnormality of sodium, potassium, and calcium If three or more patients experience DLT at a given dose level, then the previous dose level will be considered as the MTD. | 6 weeks | 
| maximum-tolerated dose |  | 6 weeks |