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

NCT ID: NCT02495493

Last Updated: 2020-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2019-07-31

Brief Summary

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.

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.

Conditions

Gastric Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Induction DCS chemotherapy

1. Induction chemotherapy -- S-1 35mg/m2 bid day 1-14

• Docetaxel 30 mg/m2 day1, 8
• Cisplatin 30 mg/m2 day1, 8

2. 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

Group Type: EXPERIMENTAL

Induction DCS chemotherapy

Intervention Type: DRUG

docetaxel /cisplatin/S-1 followed by chemoradiotherapy (S-1/cisplatin)

Interventions

Induction DCS chemotherapy

docetaxel /cisplatin/S-1 followed by chemoradiotherapy (S-1/cisplatin)

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Sun Young Rha

Severance Hospital, Yonsei University Health System

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sun Young Rha

Role: PRINCIPAL_INVESTIGATOR

Severance Hosiptal, Yonsei University Health System

Locations

Severance Hospital, Yonsei University Health System, Yonsei Cancer Center

Seoul, , South Korea

Countries

South Korea

References

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.

Reference Type: DERIVED

PMID: 31302344 (View on PubMed)

Other Identifiers

4-2013-0548

Identifier Type: -

Identifier Source: org_study_id