S-1, Cisplatin-based Chemoradiotherapy, Induction Chemotherapy, Locally Advanced Gastric Adenocarcinoma

S-1 Plus Cisplatin-based Chemoradiotherapy After Induction Chemotherapy for Locally Advanced Gastric Adenocarcinoma : Phase II Trial

Currently, for further improved survival outcome, new cytotoxic compounds such as irinotecan and docetaxel have been combined with 5-FU/cisplatin. However, triplet regimen often burdened with higher toxicity and serious neutropenic infection. Therefore, future trials in neoadjuvant and adjuvant settings need to incorporate new molecular agents which improve efficacy, but less toxicity.

Study Overview

• Status: Completed
• Conditions: Gastric Adenocarcinoma
• Intervention / Treatment: Drug: Induction DCS chemotherapy

Detailed Description

Though a significant decrease in its incidence over the last 70 years, gastric cancer remains a significant health problem worldwide. Despite the R0 resection and adjuvant chemotherapy, the prognosis for patients with locally advanced GC remains poor, with 5-year survival rate below 60%. Therefore, active strategy to improve survival outcome is ongoing in gastric cancer. Due to the nature of gastric surgery, postsurgical recovery can be avoided by the administration of systemic therapy and/or radiation prior to the surgical procedure. Furthermore, preoperative therapy has the theoretical advantage of treating an untouched tumor (lack of treatment-induced resistance), with intact vascularization and without fibrotic remodeling of the tumor bed due to surgical trauma. These considerations addressed clinical trials incorporating neoadjuvant treatment for gastric cancer.

Preoperative chemotherapy proved superiority to surgery alone in esophagogastric junction cancer Regarding the pattern of failure, locoregional recurrence after surgical resection has been reported 20-50% of cases. To improve local control and survival outcome, chemoradiotherapy in the neoadjuvant or preoperative setting has been widely applied. In recently published meta-analysis, preoperative chemoradiotherapy combined with surgery significantly reduced the 5-year death rate compared to surgery alone (OR 0.57, P=0.001). Ajani et al reported phase II preoperative chemoradiotherapy (5-fluorouracil/cisplatin and 45 Gy radiotherapy) for localized gastric cancer. Among the 34 stage II/III gastric cancer patients, 30% had pathologic complete response and 24% had pathologic partial response (<10% residual carcinoma). Lowy et al also demonstrated 11% and 63% of complete, partial pathologic responses and preoperative chemoradiotherapy was safe and well tolerated. Based on those rationale, 28 clinical trials with neoadjuvant chemotherapy is ongoing for gastric cancer (clinicaltrial.gov) and the investigators' center is also conducting neoadjuvant chemoradiotherapy trial for localized gastric cancer (NCT01269255).Currently, for further improved survival outcome, new cytotoxic compounds such as irinotecan and docetaxel have been combined with 5-FU/cisplatin. However, triplet regimen often burdened with higher toxicity and serious neutropenic infection. Therefore, future trials in neoadjuvant and adjuvant settings need to incorporate new molecular agents which improve efficacy, but less toxicity.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University Health System, Yonsei Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed gastric cancer

• Clinical stage : - Borrmann type IV

  • Large Borrmann type III (>8cm)
  • Locally extensive nodal disease
• No evidence of metastasis
• Patients with tumor lesions which can be easily obtained fresh tumor tissue through repeated biopsies.
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
• Age≥ 20 years old.
• Performance status of Eastern Cooperative Oncology Group 0 to 2.
• Adequate organ function.

Exclusion Criteria:

1. metastatic disease
2. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ.
3. Subjects with an uncontrolled major cardiovascular disease (including AMI within 12 months, unstable angina within 6 months, over NYHA class III congestive heart failure, congenital long QT syndrome, 2° or more AV Block and uncontrolled hypertension)
4. Pregnant or lactating female
5. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Induction DCS chemotherapy; Induction chemotherapy -- S-1 35mg/m2 bid day 1-14Docetaxel 30 mg/m2 day1, 8Cisplatin 30 mg/m2 day1, 8; Chemoradiotherapy : S-1 20 mg/m2 bid (Day 1-14, 21-28) cisplatin (30 mg/m2/day, Day 1,8, 21,28), Radiotherapy 45 Gy	Drug: Induction DCS chemotherapy; docetaxel /cisplatin/S-1 followed by chemoradiotherapy (S-1/cisplatin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
pathologic response rate	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	3,6,9, 12 weeks

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Sun Young Rha, Severance Hosiptal, Yonsei University Health System

Publications and helpful links

General Publications

• Kim HS, Koom WS, Baek SE, Kim HI, Jung M, Beom SH, Kang B, Kim H, Chang JS, Choi YY, Son T, Cheong JH, Noh SH, Kim EH, Park JC, Shin SK, Lee SK, Lee YC, Shin SJ, Chung H, Jung I, Chung HC, Lim JS, Hyung WJ, Rha SY. Phase II trial of preoperative sequential chemotherapy followed by chemoradiotherapy for high-risk gastric cancer. Radiother Oncol. 2019 Nov;140:143-149. doi: 10.1016/j.radonc.2019.06.029. Epub 2019 Jul 11.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: July 8, 2015
• First Submitted That Met QC Criteria: July 10, 2015
• First Posted (Estimate): July 13, 2015

Study Record Updates

• Last Update Posted (Actual): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: 4-2013-0548