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

NCT01515748 | Completed Phase 3 Results DMC

• 3 other identifiers: DOCET_R_05153U1111-1127-0246EFC13833
• Study Type: interventional
• Target: 530
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (1)

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

  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.

  3 years

Secondary Outcomes (9)

• Overall Survival (OS)

  From randomization to date of death due to any cause (maximum duration: up to 10 years)

• Number of Participants With Post-Operative Pathological Stage Response

  Up to 10 years

• Percentage of Participants With R0 Resection

  Up to 10 years

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

  From randomization up to 30 days after last dose of study drug (maximum duration: up to 10 years)

• 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

  From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)

Study Arms (2)

Surgery + Adjuvant Chemotherapy (SC)

OTHER

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).

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

Neoadjuvant Chemotherapy +Surgery +Adjuvant chemotherapy (CSC)

EXPERIMENTAL

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).

Drug: Docetaxel (XRP6976); Drug: Oxaliplatin (SR96669); Drug: S-1 (1-(2-tetrahydrofuryl)-5-fluorouracil + 5-chloro-2, 4-dihydroxypyridine (CDHP) (Gimeracil) + Oxo (Oteracil)

Interventions

Docetaxel (XRP6976) DRUG

Pharmaceutical form:solution for infusion Route of administration: intravenous

Neoadjuvant Chemotherapy +Surgery +Adjuvant chemotherapy (CSC)

Oxaliplatin (SR96669) DRUG

Pharmaceutical form:solution for infusion Route of administration: intravenous

Neoadjuvant Chemotherapy +Surgery +Adjuvant chemotherapy (CSC)

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

Pharmaceutical form:Tablet Route of administration: Oral

Neoadjuvant Chemotherapy +Surgery +Adjuvant chemotherapy (CSC); Surgery + Adjuvant Chemotherapy (SC)

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Administrative Office

Seoul, South Korea

Location

Related Publications (2)

• Kang YK, Kim HD, Yook JH, Park YK, Lee JS, Kim YW, Kim JY, Ryu MH, Rha SY, Chung IJ, Kim IH, Oh SC, Park YS, Cheong JH, Jeong O, Heo MH, Kim HK, Park C, Yoo CH, Kang SY, Zang DY, Jang YJ, Sul JY, Kim JG, Kim BS, Beom SH, Hwang JE, Ryu SW, Kook MC, Ryoo BY, Kim H, Yoo MW, Lee NS, Lee SH, Noh SH. Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer: Updated Overall Survival Outcomes From Phase III PRODIGY. J Clin Oncol. 2024 Sep 1;42(25):2961-2965. doi: 10.1200/JCO.23.02167. Epub 2024 Jul 12.

  PMID: 38996201 DERIVED

• 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.

  PMID: 34133211 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Docetaxel; Oxaliplatin; S 1 (combination); Tegafur; gimeracil; potassium oxonate; Oxonic Acid

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Fluorouracil; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazines

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Yoon-Koo KANG, MD, PhD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2012
• First Posted: January 24, 2012
• Study Start: December 30, 2011
• Primary Completion: January 21, 2019
• Study Completion: December 13, 2021
• Last Updated: December 13, 2023
• Results First Posted: March 2, 2020

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share

Locations

KR (1)