A Phase 2 Study of Neoadjuvant Docetaxel, Oxaliplatin, S-1 in Patients With Unresectable Locally Advanced or Distant Metastasis Limited to Lymph Node Gastric Cancer

Summary

Gastric cancer is the fifth most common carcinoma in the world, and cancer-related deaths rank third. It is one of the main causes of death from cancer in Korea. The cure method for gastric cancer is radical resection, but in most patients, radical resection is impossible due to local infiltration or peripheral organ or distant metastasis. Many assisted chemotherapy has been studied to improve survival rate, and in East Asia, assisted chemotherapy after complete D2 resection is the standard treatment. In the West, on the other hand, preoperative chemotherapy and postoperative assisted chemotherapy are currently standard treatments. However, due to the limited effect of adjuvant chemotherapy, it has been reported that better clinical course can be improved by increasing anticancer intensity.

In this context, a large number of prior chemotherapy have been attempted, and prior chemotherapy has several potential effects as follows. (1) Improvement of R0 resection rate due to reduced primary cancer size, (2) early treatment for micro metastasis, (3) evaluation of treatment response rate in patients with measurable lesions, and (4) unnecessary laparotomy can be avoided in patients with biologically aggressive diseases.

Based on the efficacy of chemotherapy in the combination of docetaxel, fluoropyrimidine, and platinum in metastatic gastric cancer, the investigators conducted a preceding auxiliary anti-cancer clinical trial of docetaxel, capecitabine and cisplatin in advanced gastric cancer patients who could not be completely resected by surgery. DXP was performed 4-6 cycles before surgery with the recommended dose in phase 1-2. In a total of 49 patients, R0 resection was performed in 31 (63%), and among patients, R0 resection was improved in cases where resection was not possible due to local infiltration (71%) and in cases where para-aortic node metastasis was performed (73%).

We have reported that docetaxel, oxaliplatin, and S-1 chemotherapy (DOS) as preoperative adjuvant therapy can be safely administered in combination with D2 gastrectomy and postoperative adjuvant therapy S-1 in potentially resectable local progressive gastric cancer patients. R0 resection was achieved in 97.6% of patients, and pathological complete remission was observed in 19.5%. Based on this, a phase 3 PRODIGY study was performed to evaluate the benefit of S-1 (CSC group) as a preoperative prior chemotherapy compared to S-1 (SC group) as a postoperative adjuvant therapy in gastric cancer of cT2/3N+ or cT4Nany stage, and 0.75% of the CSC group was administered HR. In the patient group undergoing surgery, the R0 resection rate was 95% in the CSC group and 84% in the SC group. In the CSC group, the pathological complete remission rate was 10.4%.

Based on these results, a clinical trial of DOS as a preoperative chemotherapy was planned for progressive gastric cancer that could not be resected due to local progression or metastasis limited to remote lymph nodes.

Primary goal: Evaluation of R0 resection rate in patients who underwent prior chemotherapy as a clinical trial.

Secondary objective: safety evaluation, overall survival period, progression-free survival period, pathological complete remission rate, and investigation of biological markers.

Conditions

• Stomach Neoplasm

Interventions

DRUG

Docetaxel injection, oxaliplatin, S-1

As a prior chemotherapy, intravenous administration is performed every 3 weeks for docetaxel 50 mg/m2 D1, intravenous administration for oxaliplatin 100 mg/m2 D1, and oral administration twice a day for S-140 mg/m2 D1 to 14.

Sponsors & Collaborators

• Asan Medical Center

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

19 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-03-23

Primary Completion

2027-06-30

Completion

2027-12-31

Countries

• South Korea

Study Locations