Neoadjuvant Combination Chemotherapy of DCS (Cisplatin + Docetaxel + S-1) and DCF (Docetaxel + Cisplatin + 5-FU) in Patients With Locally Advanced Gastric Adenocarcinoma

Study Overview
=================
Brief Summary
-----------------
Number of patients planned The study adopted two parallel phase II studies, with the same P1 and P0 in each arm, suggested by Logan. The investigators hypothesized a target ORR of interest, P1=50, and a lower ORR, P0=25 with the treatment of DCS and DCF, respectively. Under the assumption of α-error=0.05 and β-error= 0.2, using sample size tables of A'Hern, 26 patients were required per arm to achieve the desired statistical power. Finally, taking a 20% drop-out rate into consideration, the overall number of enrolled patients was 62.

Detailed Description
-----------------
Treatment scheme Screening period: D-21 to D1 (treatment day) Preoperative screening includes EUS, laparoscopy (optional), EGD and abd-pelvic CT scan. Preoperative clinical staging is based on the guideline of Japanese Gastric Cancer Association (JGCA, 1998) Tumor response is assessed every 2 cycles (6 weeks) Treatment is repeated until,. 4 cycles progressive disease unacceptable toxicity patient's withdrawal Gastric surgery should be performed within 4 6 weeks of the last dose of chemotherapy Gastric surgery is for curative aim and should include ≥ D2 LN dissection. Patients who received R0 resection should receive at least 4-cycled adjuvant chemotherapy with 5-FU and cisplatin. Palliative chemotherapy should be indicated for inoperable progressive disease or who failed curative resection. 5-FU and oxaliplatin combination is recommended as first-line therapy. Follow up for survival is repeated every 3 months for 2 years Study period Patient enroll period for 12 months., and follow-up duration for further 12 months., resulting total study period of 24 months

Official Title
-----------------
A Randomized Phase II Trial of Neoadjuvant Combination Chemotherapy of DCS (Cisplatin + Docetaxel + S-1) and DCF (Docetaxel + Cisplatin + 5-FU) in Patients With Locally Advanced Gastric Adenocarcinoma

Conditions
-----------------
Gastric Cancer

Intervention / Treatment
-----------------
* Drug: DCS (docetaxel with cisplatin with TS-1)
* Drug: DCF (docetaxel with cisplatin with 5-FU)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically/cytologically confirmed gastric adenocarcinoma Age 18 to 70 years old ECOG performance Status 0 1 Preoperative clinical staging by Japanese Gastric Cancer Association (JGCA): cT3N2 (IIIB), cT4N0-3 (IIIA IV), M0, P0, H0, CY0 No pretreatment (radiotherapy or chemotherapy) for gastric cancer Adequate organ function Hb ≥ 9.0 g/dL WBC ≥ 4,000/µL ANC ≥ 2,000/µL (*ANC = Neutrophil segs ＋ Neutrophil bands) Platelet ≥ 100 × 103/ µL Total bilirubin: ≤ 1.5 × UNL CCr ≥ 60 ml/min (by laboratory or Cockcroft-Gault Formula) AST/ALT, ALP: ≤ 2.5 × UNL Written informed consent Exclusion Criteria: Distant metastasis on diagnosis cT1-2 Cancer of gastroesophageal junction (GEJ) Poor oral intake or absorption deficiency syndrome Gastric outlet obstruction, perforation or bleeding Medically uncontrollable chronic illness or infection Pregnant or lactating women, women of childbearing potential not employing adequate contraception History of clinically significant cardiac disease Past or concurrent history of neoplasm last < 5 year other than gastric cancer Prior gastrectomized patients Concomitant administration of any other experimental drug under investigation Peripheral neuropathy ≥ NCI-CTC grade 2

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: DCS<br>DCS: docetaxel with cisplatin with TS-1 | Drug: DCS (docetaxel with cisplatin with TS-1)<br>* S-1: 70 mg/m2 #2 bid PO, D1-14 Docetaxel 30 mg/m2 IVF (for 1 hr) D1 and D8 Cisplatin 30 mg/m2 IVF (for 2 hrs, without hydration) D1 and D8, repeated by 3 weeks.<br>* Other names: TS-1;|
| Active Comparator: DCF<br>DCF : docetaxel with cisplatin with 5-FU | Drug: DCF (docetaxel with cisplatin with 5-FU)<br>* 5-FU: 1,000 mg/m2 CI, D1-3 Docetaxel 60 mg/m2 IVF (for 1 hr) D1 followed by Cisplatin 60 mg/m2 IVF (for 2 hrs, with hydration) D1, repeated by 3 weeks. Intercycle or intracycle dose modification is indicated if ≥G3 hematologic toxicity (except anemia) or ≥G3 non-hematologic toxicity (except alopecia) treatment is repeated until 4 cycles<br>* Other names: CDDP;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RECIST(Response Evaluation Criteria in Solid Tumors) | safety : every cycle adverse event/serious adversr event evaluation from NCI-CTC(version 3.0) efficacy : tumor response is assessed every 2 cycles (6weeks) -> tumor response assessment(RECIST<Response Evaluation Criteria in Solid Tumor> 1.0 version use) | written in the description part below | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
unresectable, locally advanced