Phase II Study of DC Versus 5-FU/CF as Chemotherapy and Concurrent Chemoradiotherapy for Locally Advanced Gastric Cancer

Phase 2

• Conditions: Gastric Cancer
• Interventions: Drug: concurrent chemoradiotherapy with 5-FU/CF; Drug: DC; Radiation: radiation

• Registration Number: NCT01889303
• Lead Sponsor: Wuhan University

Brief Summary

Concurrent chemoradiotherapy has been demonstrated a significant improvement in overall survival and disease-free survival according to Intergroup Trial 0116 in patients with gastric cancer after surgical resection. However,there are still many patients experiencing local recurrence or distant metastasis after adjuvant chemotherapy and concurrent chemoradiotherapy for locally advanced gastric cancer after resection. The optimal and standard regimen for adjuvant treatment has not been established in locally advanced gastric cancer yet.The investigators designed the trial to investigate the efficacy and safety of docetaxel plus cisplatin regimen as adjuvant chemotherapy and concurrent chemoradiotherapy regimen compared with classical FOLFOX6 regimen as adjuvant chemotherapy and 5-FU/CF as chemoradiotherapy in patients of locally advanced gastric cancer after D2 radical resection.

Detailed Description

In Intergroup 0116 trial, 5-FU plus CF regimen was used as adjuvant chemotherapy and concurrent chemoradiotherapy in patients with resected gastric cancer.But 33 percent of those in the chemoradiotherapy group had distant relapses. Docetaxel plus cisplatin regimen as adjuvant chemotherapy for gastric cancer has been proofed Safe and Effective in many clinical trials about gastric cancer. The purpose of this study is to evaluate efficacy and safety of docetaxel plus cisplatin regimen as adjuvant chemotherapy and concurrent chemoradiotherapy regimen compared with classical FOLFOX6 regimen as adjuvant chemotherapy and 5-FU/CF as chemoradiotherapy in patients of locally advanced gastric cancer after D2 radical surgery. The investigators hope the new interventions can reduce the rate of distant metastasis and have more clinical benefit.

Study Timeline

• Study Start: 2013-05
• Study First Submitted: 2013-06-02
• Study First Submitted QC: 2013-06-27
• Study First Posted: 2013-06-28
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-29
• Last Update Posted: 2022-02-14
• Primary Completion: 2023-06-01
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Written informed consent
2. Age > 19
3. Histologically proven gastric or gastroesophageal adenocarcinoma
4. ≥ D2 lymph node dissection, curative gastrectomy,
5. Stage T4 with or without any positive LN (AJCC 2010) ，No distant metastasis(M0) and after D2 radical gastrectomy
6. KPS≥70 or ECOG 0-2
7. R0 resection,
8. Adequate bone marrow functions (WBC≥4.0×109/L，GRAN≥2.0×109/L，Hb≥90g/L, transfusion allowed, PLT≥100×109/L )
9. No severe functional damage of major organ,and no uncontrolled or severe cardiopulmonary concurrent system disease
10. Adequate renal functions(serum creatinine ≤ 1.5×ULN ) ;liver functions (serum bilirubin ≤ 1.5×ULN, AST/ALT ≤ 2.5 times(normal value) ,serum AKP≤2.5×ULN
11. Predictive survival time longer than 6 months.

Exclusion Criteria

1. pregnant or breast-feeding women;
2. Have received preoperative neoadjuvant therapy of gastric cancer
3. Before or at the same time with other malignant tumor, and underwent chemotherapy, immune, and biological treatment and radiation therapy;with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
4. uncontrolled mental disease
5. Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, no myocardial infarction within the last 12 months, unstable angina pectoris, or significant arrhythmia)
6. Active infection requiring antibiotics
7. Resection margin (+) at permanent pathology
8. Peripheral neuropathy symptoms, NCI class > 1
9. severe malnutrition or severe anemia
10. uncontrolled Primary brain tumors or the central nervous system disease
11. Known hypersensitivity against any of the study drugs
12. Pathologic stage I-IIa or IV (according to AJCC 2010)
13. Inadequate surgery including D0, D1 resection, dissected LNs less than 12
14. Concurrent treatment with other experimental drugs or other anti-cancer therapy, or treatment within a clinical trial within 30 days prior to trial entry

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	concurrent chemoradiotherapy with 5-FU/CF	chemotherapy regimen:Oxaliplatin 85mg/m2 IV d1,Leucovorin 400mg/m2 IV d1,5-FU 400mg/m2 IV bolus d1 ,then 2400mg/m2 over 46h continuous infusion Q2W for 3 cycles → 5-FU 400 mg/m2 IV and Leucovorin 20 mg/m2 IV on the first four and the last three days of radiotherapy + RT 45Gy (5weeks)→ Rest for 4 weeks →Oxaliplatin 85mg/m2 IV d1,Leucovorin 400mg/m2 IV d1,5-FU 400mg/m2 IV bolus d1 ,then 2400mg/m2 over 46h continuous infusion Q2W for 3 cycles. Radiation: concurrent chemoradiotherapy with 5-FU/CF.Radiotherapy consisted of 45Gy of radiation at 1.8Gy per day, five days per week for five weeks.
Arm A	radiation	chemotherapy regimen:Oxaliplatin 85mg/m2 IV d1,Leucovorin 400mg/m2 IV d1,5-FU 400mg/m2 IV bolus d1 ,then 2400mg/m2 over 46h continuous infusion Q2W for 3 cycles → 5-FU 400 mg/m2 IV and Leucovorin 20 mg/m2 IV on the first four and the last three days of radiotherapy + RT 45Gy (5weeks)→ Rest for 4 weeks →Oxaliplatin 85mg/m2 IV d1,Leucovorin 400mg/m2 IV d1,5-FU 400mg/m2 IV bolus d1 ,then 2400mg/m2 over 46h continuous infusion Q2W for 3 cycles. Radiation: concurrent chemoradiotherapy with 5-FU/CF.Radiotherapy consisted of 45Gy of radiation at 1.8Gy per day, five days per week for five weeks.
Arm B	radiation	chemotherapy regimen:Docetaxel 75mg iv D1,Cisplatin 75mg iv D1 ,Q3W x 2 cycles → Docetaxel 35mg iv D1,Cisplatin 25mg iv D1,QWx4 cycles(but rest in the 4th week during RT) + RT 45Gy (5weeks) for concurrent chemoradiotherapy→ Rest for 4 weeks → Docetaxel 75mg iv D1,Cisplatin 75mg iv D1 ,Q3W x 2 cycles Radiation: concurrent chemoradiotherapy with DC.Radiotherapy consisted of 45Gy of radiation at 1.8Gy per day, five days per week for five weeks.
Arm B	DC	chemotherapy regimen:Docetaxel 75mg iv D1,Cisplatin 75mg iv D1 ,Q3W x 2 cycles → Docetaxel 35mg iv D1,Cisplatin 25mg iv D1,QWx4 cycles(but rest in the 4th week during RT) + RT 45Gy (5weeks) for concurrent chemoradiotherapy→ Rest for 4 weeks → Docetaxel 75mg iv D1,Cisplatin 75mg iv D1 ,Q3W x 2 cycles Radiation: concurrent chemoradiotherapy with DC.Radiotherapy consisted of 45Gy of radiation at 1.8Gy per day, five days per week for five weeks.

Primary Outcome Measures

Name	Time	Method
Disease free survival	2,3 year	efficacy of docetaxel plus cisplatin regimen as adjuvant chemotherapy and concurrent chemoradiotherapy for locally advanced gastric cancer patients in this trial is defined as 2 or 3 year disease free survival

Secondary Outcome Measures

Name	Time	Method
Overall survival(OS)	3 year	efficacy of docetaxel plus cisplatin regimen as adjuvant chemotherapy and concurrent chemoradiotherapy for locally advanced gastric cancer patients in this trial is defined as 3-year overall survival
Local and regional control rate	2,3 year	efficacy of docetaxel plus cisplatin regimen as adjuvant chemotherapy and concurrent chemoradiotherapy for locally advanced gastric cancer patients in this trial is defined as local and regional control rate
feasibility (including adverse events )	3year	feasibility of docetaxel plus cisplatin regimen as adjuvant chemotherapy and concurrent chemoradiotherapy for locally advanced gastric cancer patients in this trial is defined as toxicities and rate of patients complete concurrent chemoradiation according to protocol.

Trial Locations

Locations (1)

Zhongnan Hospital of Wuhan University; 🇨🇳 Wuhan, Hubei, China