Clinical trial NCT01515748: Docetaxel+Oxaliplatin+S-1 (DOS) Regimen as Neoadjuvant Chemotherapy in Advanced Gastric Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-01-24
Enrollment: 530
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion criteria :

* Participants with new histologically confirmed, newly diagnosed, localized gastric or gastro-oesophageal adenocarcinoma, that is considered resectable.
* Participants with clinical stage (T2-3/N(+), T4/N(+/-):N positive means greater than or equal to \[\>=\] 8 in hour axis).
* Signed informed consent.

Exclusion criteria:

* Aged less than (\<) 20 years or \>= 76 years. Performance status \>=2 in Eastern Cooperative Oncology Group (ECOG) scale
* The participants who had the history of other malignancy within the last five years except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix which had been already successfully treated.
* Previous surgery on neoplasm of stomach.
* Participants who did not completely recovered from surgery.
* Distant metastases (M1) to other organs including distant nodal groups (retropancreatic, para-aortic, portal, retroperitoneal, mesenteric node). severe/unstable angina, coronary artery bypass graft, congestive heart failure, transient ischemic attack within 6 months prior to enrollment in the study.
* Any previous palliative, adjuvant or neoadjuvant chemotherapy and/or radiotherapy and/or immunotherapy, for the currently treated gastric cancer.
* Participants with active infection or sepsis.
* Intolerance of oral taking or malabsorption: lack of physical integrity of the upper gastrointestinal tract or those who have malabsorption syndrome likely to influence absorption of S-1. Ileus, chronic inflammatory intestinal disease or extensive resection of the small intestine and other disorders which limit drug resorption. This includes gastric dumping syndrome, indications of accelerated passage through the small intestine and indications of resorption disorders after intestinal surgery.
* Greater than or equal to grade 2 severe tumour haemorrhage.
* Simultaneous participation in another study, or participation in another study within 4 weeks of commencement of this study.
* Pregnant or lactating participants.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Percentage of Participants With 3-Year Progression-Free Survival (PFS), as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)1.1
timeFrame: 3 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization to date of death due to any cause (maximum duration: up to 10 years)
measure: Number of Participants With Post-Operative Pathological Stage Response
timeFrame: Up to 10 years
measure: Percentage of Participants With R0 Resection
timeFrame: Up to 10 years
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From randomization up to 30 days after last dose of study drug (maximum duration: up to 10 years)
measure: 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
timeFrame: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)
measure: Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3
timeFrame: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)
measure: Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3
timeFrame: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)
measure: 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
timeFrame: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)
measure: Number of Participants With Shift of Laboratory Parameters (Creatinine Clearance [Chronic Kidney Disease]) From Baseline Grade to Worst NCI-CTCAE Grade >=3
timeFrame: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Administrative Office
Study officials:
affiliation: Asan Medical Center
name: Yoon-Koo KANG, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kang YK, Yook JH, Park YK, Lee JS, Kim YW, Kim JY, Ryu MH, Rha SY, Chung IJ, Kim IH, Oh SC, Park YS, Son T, Jung MR, Heo MH, Kim HK, Park C, Yoo CH, Choi JH, Zang DY, Jang YJ, Sul JY, Kim JG, Kim BS, Beom SH, Cho SH, Ryu SW, Kook MC, Ryoo BY, Kim HK, Yoo MW, Lee NS, Lee SH, Kim G, Lee Y, Lee JH, Noh SH. PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer. J Clin Oncol. 2021 Sep 10;39(26):2903-2913. doi: 10.1200/JCO.20.02914. Epub 2021 Jun 16.