Randomized phase II trial of chemoradiotherapy with S-1 versus gemcitabine and S-1 combination therapy as neoadjuvant treatment in patients with resectable pancreatic cancer

JRCT ID: jRCTs041180051

Registered date:22/02/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: resectable pancreatic cancer
• Date of first enrollment: 31/10/2014
• Target sample size: 100
• Study type: Interventional

Intervention(s)

arm A: chemoradiotherapy with S-1 as neoadjuvant treatment
arm B: Gemcitabine and S-1 combination therapy as
neoadjuvant treatment

Outcome(s)

• Primary Outcome: 2-year progression-free survival
• Secondary Outcome: overall survival (2-year survival rate), R0 or 1 resection rate, pathological response rate, adverse event of neoadjuvant therapy, morbidity rate of surgery, non-hematologic adverse event of grade 4, early mortality rate, treatment-related mortality rate

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 79age old
• Gender: Both

Include criteria

1) Resectable invasive ductal carcinoma of the pancreas (according to the General Rules for the Study of Pancreatic Cancer, the sixth edition, excluding intraductal papillary mucinous carcinoma and acinar cell carcinoma) diagnosed based on the images of contrast abdominal CT scan mainly
2) Conformity with either a) or b) criterion
a) Adenocarcinoma proven by biopsy or cytology*1, which is consistent with papillary adenocarcinoma, tubular adenocarcinoma, poorly differentiated adenocarcinoma, or adenosquamous carcinoma on the imaging diagnosis
b) Although there is no pathological evidence, cancer is evident based on the imaging diagnosis and a high tumor marker value (only in pancreatic body and tail cancer)*2.
*1: Cytology of class IV or V is eligible.
*2: If a patient turns to be inoperable, pathological confirmation of cancer by biopsy or cytology is necessary.
3) A radiologist has to confirm that an estimated radiation field*3 is within 10x10 cm in size including a primary lesion and metastatic nodes (PET-positive nodes are considered to be metastatic) on abdominal CT or MRI.
*3: Prophylactic irradiation for regional nodes is not performed in this study.
4) No active gastric or duodenal ulcer
5) No findings of gastrointestinal invasion conformable with a) or b)
a) Findings of mucosal invasion of the stomach or duodenum by endoscopy
b) Protrusion of the tumor into the gastric or duodenal lumen by CT scan
6) Age of >20 or <79 years on enrollment
7) ECOG performance status of 0 or 1 (PS has to be written in the medical record)
8) Adequate oral intake
9) No past history of irradiation for the abdomen
10) No past history of chemotherapy within 3 years
11) No past history of treatment for pancreatic cancer
12) All the following conditions have to be fulfilled. All data have to be the newest and examined within 7 days prior to enrollment.
(1) White blood cell >3,000
(2) Hemoglobin >9.0 g/dL
(3) Platelet >100,000/mm3
(4) Albumin >3.0g/dL
(5) Total bilirubin <2.0mg/dL without biliary decompression*4 or <3.0mg/L with biliary decompression
(6) AST <100IU/L without biliary decompression*4 or 150IU/L with biliary decompression
(7) ALT <100IU/L without biliary decompression*4 or 150IU/L with biliary decompression
(8) Serum creatinine <1.2mg/dL
(9) Creatinine clearance*5 >50mL/min/body
*4: Percutaneous biliary drainage (PTCD, stent) or endoscopic biliary drainage (ENBD, ERBD, stent). Metallic stent is not recommended.
*5: Estimated creatinine clearance has to be 50mL/min or more by the Cockcroft-Gault formula. If an estimated creatinine level is below 50mlL/min, an actual measurement level of >50mL/min is required. The Cockcroft-Gault formula is following: Ccr is [(140-age)xbody weight (Kg)]/[72xserum creatinine level (mg/dL)] in men, Ccr is 0.85x[(140-age)xbody weight (Kg)]/[72xserum creatinine level (mg/dL)] in women
13) Written informed consent of the patient

Exclude criteria

1) Past medical history of usage of gemcitabine or fluoropyrimidine drugs
2) Usage of flucytosine, phenytoin or warfarin potassium
3) Pulmonary fibrosis or interstitial pneumonia, evident by chest X-ray or symptomatic
4) Moderate amount of plural effusion or ascites
5) Watery diarrhea
6) Severe comorbidity (heart failure, renal failure, hepatic failure, intestinal paresis, ileus, uncontrollable diabetes mellitus, etc)
7) Cardiac infarction within 6 months
8) Active double cancer (synchronous double cancer or metachronous double cancer within 3 years excluding carcinoma in situ or mucosal cancer)
9) Active infectious disease excluding hepatitis B (pyrexia of over 38 degree, etc)
10) Blood transfusion within 2 weeks prior to enrollment
11) Pregnant, possibly pregnant or breast-feeding women. Men who wish his partner to be pregnant
12) Mental disease or mental symptom which makes participation to the study difficult
13) Continuous systemic steroid treatment (per-oral or infusional)
14) Severe drug allergy
15) Contraindication of both iodine-based and gadolinium-based drugs due to drug allergy
16) Patients who are considered inappropriate to participate this study safely by physicians

Related Information

• Primary Sponsor: Uesaka Katsuhiko
• Source(s) of Monetary Support: Taiho Pharmaceutical Co., Ltd.
• Secondary ID(s): UMIN000014894