Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Docetaxel

Fluorouracil

Oxaliplatin

Tegafur

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 milligrams per square meter (mg/m\^2) administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after End-of-Treatment (EOT) until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).

Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 intravenously (IV) for greater than or equal to (\>=)1 hour (hr) on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).

Pharmaceutical form:solution for infusion Route of administration: intravenous

Docetaxel (XRP6976)

Oxaliplatin (SR96669)

Pharmaceutical form:Tablet Route of administration: Oral

S-1 (1-(2-tetrahydrofuryl)-5-fluorouracil + 5-chloro-2, 4-dihydroxypyridine (CDHP) (Gimeracil) + Oxo (Oteracil)

Yoon-Koo KANG, MD, PhD

Primary Objective:

- To compare the 3-year progression free survival (PFS) in the two treatment arms.

Secondary Objectives:

* Overall survival (OS).
* Postoperative pathological stage and R0 (complete) resection rate.
* Safety: Toxicities associated with neoadjuvant chemotherapy, surgery, morbidity/mortality, toxicity of adjuvant chemotherapy.

Participants in the neoadjuvant chemotherapy arm were treated for 3 cycles (1 cycle is 21 days) before surgery and treated for a year with S-1. Participants in the adjuvant chemotherapy arm underwent surgery and were treated for a year with S-1. All participants were followed during and after the study treatment until death or disease progression, whichever comes first.

Docetaxel+Oxaliplatin+S-1 (DOS) Regimen as Neoadjuvant Chemotherapy in Advanced Gastric Cancer

A Phase III, Open-labelled, Randomised Study of Neoadjuvant Docetaxel+Oxaliplatin+S-1 (DOS) + Surgery + Adjuvant S-1 Versus Surgery + Adjuvant S-1 in Patients With Resectable Advanced Gastric Cancer

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

PFS was defined as the time from randomization to objective tumor progression, or recurrence or death. Progressive disease (PD) was defined as follows: 1) In Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) Arm, PD was determined according to the RECIST 1.1 Criteria during the neo-adjuvant chemotherapy period; 2) Irrespective of curative resection, if an intraoperative distant metastasis was observed or a distant metastasis was reported from pathology, it was considered PD; 3) If residual cancer cells were visually identified at the resection margin during surgery but could not be completely resected (R2), it was considered PD; 4) If residual cancer cells were finally confirmed at the resection margin during postoperative histology (R1), it was considered PD; 5) In case of finding a recurrence/distant metastasis or a new lesion during follow-up after R0 complete resection, it was defined as the first tumor assessment date when it was observed.

OS was defined as the time from randomization to death due to any cause. Analyzed using Kaplan-Meier method.

TNM pathological stage was determined according to standardized histopathology and the American Joint Committee on Cancer (AJCC) staging system 7th Edition (Stages 0,IA,IB,IIA,IIB,IIIA,IIIB,IIIC and IV). Stage 0=carcinoma in situ with no metastatic potential; Stage IA=T1N0M0; Stage IB=T2N0M0,T1N1M0; Stage IIA=T3N0M0,T2N1M0,T1N2M0;Stage IIB=T4aN0M0,T3N1M0,T2N2M0,T1N3M0;Stage IIIA=T4aN1M0,T3N2M0,T2N3M0;Stage IIIB=T4bN0-1M0,T4aN2M0,T3N3M0;Stage IIIC=T4bN2-3M0, T4aN3M0 and Stage IV= distant metastases (M1) at diagnosis; where "T" denotes "tumor size" where T1: tumor invades lamina propria, muscularis mucosae, or submucosa; T2: invades muscularis propria; T3: invasion of subserosa; T4: T4a: penetrate serosa (visceral peritoneum) T4b: invade adjacent tissue and " N" denotes "nodes affected" where N1:1-2 positive lymph nodes; N2:3-6 positive lymph nodes; N3: 7 or more positive lymph nodes and "M" denotes metastases where M0: no distant metastases. Higher stages indicates worse outcome.

Tumor condition was explained according to the Residual Tumor (R) Classification: R0; No residual cancer (negative cross-section), R1; Microscopically observed residual cancer (positive cross-section), R2; Macroscopically observed residual cancer.

TEAEs were defined as adverse events (AE) that appeared or worsened during the treatment period (up to 30 days after the last dose of the investigational product). SAE was an AE or adverse drug reaction at any dose of the investigational product that corresponded to one of the following: resulting in death or is life threatening; requiring in-patient hospitalization or prolongation of existing hospitalization; resulting in persistent or significant disability of dysfunction; resulting in congenital anomaly or birth defect; important medical event.

NCI-CTCAE version 4.03 was used to determine Grade(Gr),where Gr refers to severity of AE:Gr 1:mild; asymptomatic/mild symptoms; Gr 2:moderate;minimal; Gr 3:severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Hemoglobin(Hb)(Anemia) were based on Gr1:\<lower limit of normal (LLN)-10.0g/dL; Gr2:\<10.0-8.0g/dL; Gr3:\<8.0g/dL; Gr4:life-threatening consequences;Gr5:death. Hb increased:Gr 1:increase(incr.) in \>0-2g/dL above upper limit of normal(ULN);Gr2: incr. in \>2-4g/dL above ULN; Gr3:incr. in \>4gm/dL above ULN. White blood cell (WBC) decreased: Gr1:\<LLN - 3000/mm\^3;Gr2: \<3000-2000/mm\^3; Gr3:\<2000-1000/mm\^3;Gr4:\<1000/mm\^3. WBC (Leukocytosis):Gr3:\>100,000/mm\^3, Gr4:clinical manifestations of leucostasis;Gr5:Death. Abnormal Neutrophil count (ANC):- Gr1:\<LLN-1500/mm\^3;Gr2:\<1500-1000/mm\^3; Gr3: \<1000-500/mm\^3; Gr4:\<500/mm\^3. Platelet count decreased: Gr1:\<LLN-75,000/mm\^3;Gr2:\<75,000-50,000/mm\^3;Gr3:\<50,000-25,000/mm\^3;Gr4:\<25,000/mm\^3.

NCI-CTCAE version 4.03 was used to determine Gr,where Gr refers to severity of AE: Gr 1: mild; asymptomatic/mild symptoms; Gr 2: moderate; minimal; Gr 3:severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Sodium (Hyponatremia) were based on Gr1: \<LLN-130 mmol/L; Gr3: \<130-120 mmol/L; Gr4: \<120 mmol/L; life-threatening consequences; Gr5: death. Sodium (Hypernatremia):Gr 1: \>ULN-150 mmol/L; Gr2: \>150-155 mmol/L; Gr3:\>155-160 mmol/L;hospitalization; Gr4: \>160 mmol/L; life-threatening consequences; Gr5: Death. Potassium (Hypokalemia): Gr 1: \<LLN-3.0 mmol/L; Gr2: \<LLN-3.0 mmol/L; symptomatic; intervention indicated; Gr3: \<3.0-2.5 mmol/L; hospitalization indicated; Gr4: \<2.5 mmol/L; life-threatening consequences; Gr5: Death; Potassium(Hyperkalemia): Gr 1: \>ULN-5.5 mmol/L; Gr2: \>5.5-6.0 mmol/L; Gr3: \>6.0-7.0 mmol/L; hospitalization indicated; Gr4: \>7.0 mmol/L; life-threatening consequences; Gr5: Death.

NCI-CTCAE version 4.03 was used to determine Gr,where Gr refers to severity of AE:Gr 1:mild; asymptomatic/mild symptoms; Gr 2:moderate;minimal; Gr 3:severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Calcium(Hypocalcemia) were based on Gr1: Corrected serum calcium of \<LLN-8.0 mg/dL; Gr2: Corrected serum calcium of \<8.0-7.0 mg/dL; Gr3: Corrected serum calcium of \<7.0-6.0 mg/dL ; Gr4: Corrected serum calcium of \<6.0 mg/dL;Gr5:death. Calcium(Hypercalcemia):Gr 1: Corrected serum calcium of \>ULN -11.5 mg/dL; Gr2: Corrected serum calcium of \>11.5-12.5 mg/dL; Gr3: Corrected serum calcium of \>12.5-13.5 mg/dL; Gr4: Corrected serum calcium of \>13.5 mg/dL;Gr5:Death. Creatinine increased: Gr 1: \>1-1.5\*baseline; \>ULN-1.5\*ULN; Gr2: \>1.5-3.0\*baseline; \>1.5-3.0\*ULN; Gr3: \>3.0 baseline; \>3.0-6.0\*ULN; Gr4: \>6.0 x ULN. Albumin(Hypoalbuminemia): Gr 1: \<LLN-3 g/dL; Gr2: \<3-2 g/dL; Gr3: \<2 g/dL; Gr4:life-threatening consequences;Gr5:Death.

NCI-CTCAE version 4.03 was used to determine Gr, where Gr refers to severity of AE: Gr 1:mild; asymptomatic/mild symptoms; Gr 2:moderate; minimal; Gr 3:severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Aspartate and alanine aminotransferase increased were based on Gr1: \>ULN-3.0\*ULN; Gr2: \>3.0-5.0\*ULN; Gr3: \>5.0-20.0\*ULN; Gr4: \>20.0\*ULN. Blood bilirubin increased: Gr1: \>ULN-1.5\*ULN; Gr2 \>1.5-3.0\*ULN; Gr3: \>3.0-10.0\*ULN; Gr4: \>10.0\*ULN. Alkaline phosphatase increased: Gr1: \>ULN-2.5\*ULN; Gr2: \>2.5-5.0\*ULN; Gr3: \>5.0-20.0\*ULN; Gr4: \>20.0\*ULN. Glucose (Hypoglycemia): Gr 1: \<LLN-55 mg/dL; Gr2: \<55-40 mg/dL;Gr3: \<40-30 mg/dL; Gr4: \<30 mg/dL; Gr5:Death. Glucose (Hyperglycemia): Gr 1: Fasting glucose value \>ULN-160 mg/dL; Gr2: Fasting glucose value \>160-250 mg/dL; Gr3: \>250-500 mg/dL; Gr4: \>500 mg/dL; Gr5: Death.

NCI-CTCAE version 4.03 was used to determine Gr, where Gr refers to severity of AE: Gr 1: mild; asymptomatic/mild symptoms; Gr 2: moderate; minimal; Gr 3: severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Creatinine Clearance(Chronic kidney disease) were based on: Gr 1: estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) \<LLN-60ml/min/1.73 m\^2; Gr2: eGFR or CrCl 59-30 ml/min/1.73 m\^2; Gr3: eGFR or CrCl 29-15 ml/min/1.73 m\^2; Gr4: eGFR or CrCl \<15 ml/min/1.73 m\^2; Gr5: Death.

Sanofi

All-Cause Mortality data collected during the study was assessed for all randomized population. SAE and other AE data was assessed for safety population. Disease progression related death were not reported as AE.

Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).

Surgery + Adjuvant Chemotherapy (SC)

Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 IV for \>= 1 hr on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).

Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC)

Total

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Analysis was performed on Intent-to-Treat (ITT) population which included all randomized participants.

Trial Transparency Team

Analysis was performed using Kaplan-Meier method. Comparison was stratified based on site and TNM classification (T4/N-, T2/N+, T3-4/N+).

Full Analysis Set (FAS): included all randomized participants who satisfied inclusion/exclusion criteria and had at least one tumor assessment after baseline visit (Day 0). The CSC Arm included all participants exposed to at least one dose of Docetaxel+Oxaliplatin+S-1 investigational products. The SC Arm included all participants who had surgery.

Percentage of Participants With 3-Year Progression-Free Survival (PFS), as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)1.1

Analysis was performed on FAS population.

Overall Survival (OS)

Stage 0

Stage IA

Stage IB

Stage IIA

Stage IIB

Stage IIIA

Stage IIIB

Stage IIIC

Stage IV

Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Number of Participants With Post-Operative Pathological Stage Response

Percentage of Participants With R0 Resection

Any TEAE

Any treatment emergent SAE

TEAEs leading to permanent discontinuation

Analysis was performed on safety population which included participants who were administered at least one dose of the investigational product.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Hb(Anemia) Gr 0 at Baseline to Gr >=3

Hb(Anemia) Gr 1 at Baseline to Gr >=3

Hb(Anemia) Gr 2 at Baseline to Gr >=3

Hb(Anemia) Gr 3 at Baseline to Gr >=3

Hb(Anemia) Gr 4 at Baseline to Gr >=3

Hb(Anemia) Gr 5 at Baseline to Gr >=3

Hb increased Gr 0 at Baseline to Gr >=3

Hb increased Gr 1 at Baseline to Gr >=3

Hb increased Gr 2 at Baseline to Gr >=3

Hb increased Gr 3 at Baseline to Gr >=3

Hb increased Gr 4 at Baseline to Gr >=3

Hb increased Gr 5 at Baseline to Gr >=3

WBC decreased Gr 0 at Baseline to Gr >=3

WBC decreased Gr 1 at Baseline to Gr >=3

WBC decreased Gr 2 at Baseline to Gr >=3

WBC decreased Gr 3 at Baseline to Gr >=3

WBC decreased Gr 4 at Baseline to Gr >=3

WBC decreased Gr 5 at Baseline to Gr >=3

WBC (Leukocytosis) Gr 0 at Baseline to Gr >=3

WBC (Leukocytosis) Gr 1 at Baseline to Gr >=3

WBC (Leukocytosis) Gr 2 at Baseline to Gr >=3

WBC (Leukocytosis) Gr 3 at Baseline to Gr >=3

WBC (Leukocytosis) Gr 4 at Baseline to Gr >=3

WBC (Leukocytosis) Gr 5 at Baseline to Gr >=3

ANC Gr 0 at Baseline to Gr >=3

ANC Gr 1 at Baseline to Gr >=3

ANC Gr 2 at Baseline to Gr >=3

ANC Gr 3 at Baseline to Gr >=3

ANC Gr 4 at Baseline to Gr >=3

ANC Gr 5 at Baseline to Gr >=3

Platelet count decreased Gr0 at Baseline to Gr >=3

Platelet count decreased Gr1 at Baseline to Gr >=3

Platelet count decreased Gr2 at Baseline to Gr >=3

Platelet count decreased Gr3 at Baseline to Gr >=3

Platelet count decreased Gr4 at Baseline to Gr >=3

Platelet count decreased Gr5 at Baseline to Gr >=3

Analysis was performed on safety population.

Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3

Hyponatremia Gr 0 at Baseline to Gr >=3

Hyponatremia Gr 1 at Baseline to Gr >=3

Hyponatremia Gr 2 at Baseline to Gr >=3

Hyponatremia Gr 3 at Baseline to Gr >=3

Hyponatremia Gr 4 at Baseline to Gr >=3

Hyponatremia Gr 5 at Baseline to Gr >=3

Hypernatremia Gr 0 at Baseline to Gr >=3

Hypernatremia Gr 1 at Baseline to Gr >=3

Hypernatremia Gr 2 at Baseline to Gr >=3

Hypernatremia Gr 3 at Baseline to Gr >=3

Hypernatremia Gr 4 at Baseline to Gr >=3

Hypernatremia Gr 5 at Baseline to Gr >=3

Hypokalemia Gr 0 at Baseline to Gr >=3

Hypokalemia Gr 1 at Baseline to Gr >=3

Hypokalemia Gr 2 at Baseline to Gr >=3

Hypokalemia Gr 3 at Baseline to Gr >=3

Hypokalemia Gr 4 at Baseline to Gr >=3

Hypokalemia Gr 5 at Baseline to Gr >=3

Hyperkalemia Gr 0 at Baseline to Gr >=3

Hyperkalemia Gr 1 at Baseline to Gr >=3

Hyperkalemia Gr 2 at Baseline to Gr >=3

Hyperkalemia Gr 3 at Baseline to Gr >=3

Hyperkalemia Gr 4 at Baseline to Gr >=3

Hyperkalemia Gr 5 at Baseline to Gr >=3

Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3

Hypocalcemia Gr 0 at Baseline to Gr >=3

Hypocalcemia Gr 1 at Baseline to Gr >=3

Hypocalcemia Gr 2 at Baseline to Gr >=3

Hypocalcemia Gr 3 at Baseline to Gr >=3

Hypocalcemia Gr 4 at Baseline to Gr >=3

Hypocalcemia Gr 5 at Baseline to Gr >=3

Hypercalcemia Gr 0 at Baseline to Gr >=3

Hypercalcemia Gr 1 at Baseline to Gr >=3

Hypercalcemia Gr 2 at Baseline to Gr >=3

Hypercalcemia Gr 3 at Baseline to Gr >=3

Hypercalcemia Gr 4 at Baseline to Gr >=3

Hypercalcemia Gr 5 at Baseline to Gr >=3

Creatinine increased Gr 0 at Baseline to Gr >=3

Creatinine increased Gr 1 at Baseline to Gr >=3

Creatinine increased Gr 2 at Baseline to Gr >=3

Creatinine increased Gr 3 at Baseline to Gr >=3

Creatinine increased Gr 4 at Baseline to Gr >=3

Creatinine increased Gr 5 at Baseline to Gr >=3

Hypoalbuminemia Gr 0 at Baseline to Gr >=3

Hypoalbuminemia Gr 1 at Baseline to Gr >=3

Hypoalbuminemia Gr 2 at Baseline to Gr >=3

Hypoalbuminemia Gr 3 at Baseline to Gr >=3

Hypoalbuminemia Gr 4 at Baseline to Gr >=3

Hypoalbuminemia Gr 5 at Baseline to Gr >=3

Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3

Aspartate aminotransferase Gr0 at Baseline toGr>=3

Aspartate aminotransferase Gr1 at Baseline toGr>=3

Aspartate aminotransferase Gr2 at Baseline toGr>=3

Aspartate aminotransferase Gr3 at Baseline toGr>=3

Aspartate aminotransferase Gr4 at Baseline toGr>=3

Aspartate aminotransferase Gr5 at Baseline toGr>=3

Alanine aminotransferase Gr0 at Baseline to Gr >=3

Alanine aminotransferase Gr1 at Baseline to Gr >=3

Alanine aminotransferase Gr2 at Baseline to Gr >=3

Alanine aminotransferase Gr3 at Baseline to Gr >=3

Alanine aminotransferase Gr4 at Baseline to Gr >=3

Alanine aminotransferase Gr5 at Baseline to Gr >=3

Bilirubin increased Gr 0 at Baseline to Gr >=3

Bilirubin increased Gr 1 at Baseline to Gr >=3

Bilirubin increased Gr 2 at Baseline to Gr >=3

Bilirubin increased Gr 3 at Baseline to Gr >=3

Bilirubin increased Gr 4 at Baseline to Gr >=3

Bilirubin increased Gr 5 at Baseline to Gr >=3

Alkaline phosphatase Gr 0 at Baseline to Gr >=3

Alkaline phosphatase Gr 1 at Baseline to Gr >=3

Alkaline phosphatase Gr 2 at Baseline to Gr >=3

Alkaline phosphatase Gr 3 at Baseline to Gr >=3

Alkaline phosphatase Gr 4 at Baseline to Gr >=3

Alkaline phosphatase Gr 5 at Baseline to Gr >=3

Hypoglycemia Gr 0 at Baseline to Gr >=3

Hypoglycemia Gr 1 at Baseline to Gr >=3

Hypoglycemia Gr 2 at Baseline to Gr >=3

Hypoglycemia Gr 3 at Baseline to Gr >=3

Hypoglycemia Gr 4 at Baseline to Gr >=3

Hypoglycemia Gr 5 at Baseline to Gr >=3

Hyperglycemia Gr 0 at Baseline to Gr >=3

Hyperglycemia Gr 1 at Baseline to Gr >=3

Hyperglycemia Gr 2 at Baseline to Gr >=3

Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3

Spots Global Cancer Trial Database for Docetaxel+Oxaliplatin+S-1 (DOS) Regimen as Neoadjuvant Chemotherapy in Advanced Gastric Cancer

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