Neoadjuvant Bev Plus DOF vs DOF in LAGC and Its Association With Circulating Tumor Cell

Phase 2 Study of Neoadjuvant Bevacizumab Plus DOF Versus DOF in Local Advanced Gastric Carcinoma and Its Association With Circulating Tumor Cell

Background Local advanced gastric carcinoma (LAGC) is suggested to be potentially cured by R0 resection, and neoadjuvant chemotherapy can increase the R0 resection rate but not enough. Bevacizumab (Bev), an anti-tumor angiogenesis monoclonal antibody, combined with chemotherapy has been shown effective in advanced GC. In addition, CTC has been suggested as an indicator of the anti-tumor drugs' efficacy. Therefore, in this study, the investigators plan to evaluate the efficacy and safety of neoadjuvant Bev plus docetaxel/oxaliplatin/5-FU/CF (DOF) versus DOF in mainly gastric antrum LAGC, and to investigate whether CTC is an effectiveness indicator.

Methods 86 patients diagnosed as IIIb-IIIc GC have been enrolled and randomly assigned (1:1) to receive neoadjuvant Bev (5 mg/kg, d1) plus DOF (docetaxel, 75 mg/m2, iv, d1; oxaliplatin, 85 mg/m2, iv, d1; 5-FU, iv infusion 600 mg/m2 and iv injection 400mg/m2, d1-2; CF, 200 mg/m2, d1 and d2) or DOF each 3-week, up to 2-4 cycles preoperation, and another 2-4 cycles postoperation up to total 6 cycles. The primary endpoint is R0 resection rate. CTC was detected every 8 weeks. All patients signed the informed consent.

Study Overview

• Status: Completed
• Conditions: Locally Advanced Gastric Carcinoma
• Intervention / Treatment: Procedure: Gastrectomy; Biological: Bevacizumab; Drug: docetaxel oxaliplatin 5-FU CF

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100048
      • First Affiliated Hospital, Chinese PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed locally advanced adenocarcinoma of the stomach.
• Age of 18 to 70, Karnofsky score higher than 80.
• T3-4，N1-3，M0 (AJCC 7th), potentially resectable.
• No severe functional damage of major organ, normal blood cell, normal liver and kidney function.

Exclusion Criteria:

• Clinical findings of distant metastasis or Peritoneal carcinomatosis
• Prior systemic (chemo- or targeted) treatment. Prior radiotherapy to the upper abdomen
• Previous malignancy within 5 years, with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
• Upper gastrointestinal bleeding
• Any contraindication to treatment with docetaxel, 5-fu or oxaliplatin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: bevacizumab plus DOF; patients receive bev +DOF pre and post surgery up to total 6 cycles	Procedure: Gastrectomy; Biological: Bevacizumab; Bev (5 mg/kg, d1) every 3 weeks, up to 2-4 cycles preoperation, and another 2-4 cycles postoperation up to total 6 cycles.; Drug: docetaxel oxaliplatin 5-FU CF; docetaxel, 75 mg/m2, iv, d1; oxaliplatin, 85 mg/m2, iv, d1; 5-FU, iv infusion 600 mg/m2 and iv injection 400mg/m2, d1-2; CF, 200 mg/m2, d1 and d2 each 3-week, up to 2-4 cycles preoperation, and another 2-4 cycles postoperation up to total 6 cycles.
ACTIVE_COMPARATOR: DOF; patients receive DOF pre and post surgery up to total 6 cycles	Procedure: Gastrectomy; Drug: docetaxel oxaliplatin 5-FU CF; docetaxel, 75 mg/m2, iv, d1; oxaliplatin, 85 mg/m2, iv, d1; 5-FU, iv infusion 600 mg/m2 and iv injection 400mg/m2, d1-2; CF, 200 mg/m2, d1 and d2 each 3-week, up to 2-4 cycles preoperation, and another 2-4 cycles postoperation up to total 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
R0 resection rate	6-12 weeks after administration

Secondary Outcome Measures

Outcome Measure	Time Frame
pCR rate	Day 1 after surgery
OS	3 years after surgery
DFS	3 years after surgery
ORR	6 weeks after administration
safety of peroperative treatment and surgery	from first administration to 28 days after last administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
circulating tumor cell number change	to investigate the circulating tumor cell number change before and after neoadjuvant therapy and whether it's an effectiveness and survival predictor in LAGC	6 weeks

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: January 25, 2014
• First Submitted That Met QC Criteria: January 28, 2014
• First Posted (ESTIMATE): January 29, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): April 25, 2014
• Last Update Submitted That Met QC Criteria: April 23, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Neoplastic Processes; Neoplasm Metastasis; Stomach Neoplasms; Carcinoma; Neoplastic Cells, Circulating; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Docetaxel; Oxaliplatin; Bevacizumab
• Other Study ID Numbers: GC neoadjuvant bev CTC; BSC2013-dunan (OTHER: Beijing science commission)