A Phase 2 Trial of Optimizing Platinum-Based Chemotherapy Based on ERCC1 Expression as First-Line Treatment in Patients With Locally Advanced or Metastatic Gastric Cancer

A Prospective, Multi-Center, Randomized Control Phase 2 Trial of Optimizing Platinum-Based Chemotherapy Based on ERCC1 Expression as First-Line Treatment in Patients With Locally Advanced or Metastatic Gastric Cancer

The purpose of this study is to determine whether ERCC1(excision repair cross-complementation 1 ) expression has effects on platinum-based chemotherapy for patients with locally advanced or metastatic gastric cancer, and to explore if ERCC1 can act as a biological predictor for the individual therapy of gastric cancer

Study Overview

• Status: Terminated
• Conditions: Stomach Neoplasms
• Intervention / Treatment: Drug: Capecitabine+Cisplatin; Drug: Docetaxel+Capecitabine

Detailed Description

This is a prospective, multi-center, randomized control clinical trial, aimed to demonstrate if ERCC1 expression could predict the efficacy of platinum-based chemotherapy in patients with locally advanced or metastatic gastric cancer. A total of 180 patients are planned to be enrolled into the study. ERCC1 protein expression in paraffin-embedding tumor tissue is examined by immunohistochemistry (IHC). Patients with low ERCC1 expression (group L) will be treated with XP regimen. Patients with high ERCC1 expression will be randomized into group H-A or group H-B, and be treated with XP or DX regimen, respectively. The primary end point is progression free survival (PFS), and the secondary end points include the median overall survival, objective response rate (ORR),disease control rate(DCR), duration of response, safety(number and degree of adverse events), and the quality of life (QOL).

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Anshan, Liaoning, China
      • The Fourth Hospital of Anshan
    • Dalian, Liaoning, China
      • The First Hospital of Dalian Medical University
    • Dalian, Liaoning, China
      • The Second Hospital of Dalian Medical University
    • Jinzhou, Liaoning, China
      • The First Hospital of Liaoning Medical University
    • Shenyang, Liaoning, China, 110001
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China
      • Shengjing Hospital of China Medical University
    • Shenyang, Liaoning, China
      • Liaoning Tumor Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18y≤Age≤65y, male or female
• KPS≥70
• Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable locally advanced or recurrent and/or metastatic disease
• At least one measurable lesion, according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), assessed using imaging techniques (CT or MRI)
• No prior anti-tumor treatment or an interval of at least 6 months from the last adjuvant chemotherapy, and an interval of at least 4 weeks from the last radical radiation therapy
• No major organ disorder, with normal liver, kidney and heart function
• Laboratory test must meet the following criteria: hemoglobin (HGB) ≥90g/L, neutrophil count ≥1.5×109/L, platelet count ≥100×109/L, creatinine clearance rate (CCr) ≥60ml/min, total bilirubin (TBil) ≤1.5 upper normal limitation (UNL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 UNL (For patients with liver metastasis, the AST/ALT must be ≤5.0 UNL), blood glucose ≤11.1 mmol/L
• Life expectancy of at least 12 weeks
• Signed informed consent
• For women with child bearing potential, a negative serum or urine pregnancy test result should be obtained before enrollment

Exclusion Criteria:

• Progression from prior palliative treatment with capecitabine- or docetaxel-based regimen
• Serious uncontrolled systemic illness or medical condition: congestive heart failure, unstable angina, history of documented myocardial infarction within 6 months, uncontrolled hypertension and high risk uncontrollable arrhythmias; Obvious neurological or mental abnormalities including mental disorder, epileptic dementia, which affect compliance; Uncontrolled acute infections; Uncontrolled peptic ulcer, diabetes or other contraindication for corticosteroid therapy
• Inability to take or absorb oral medicine
• Concurrent administration of any other investigational drug, or have been enrolled in other clinical trial with investigational drug treatment within the 30 days of start of study treatment
• Presence of neuropathy ≥grade 1 according to NCI-CTCAE V4.0
• Hypersensitivity or known or suspicious allergic to any of the study drugs
• Pregnant or lactated women
• Unsuitable for the study or other chemotherapy determined by investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: H-A: ERCC1 High Expression Group A; XP：Capecitabine+Cisplatin	Drug: Capecitabine+Cisplatin; Cisplatin 75mg/m2, d1; Capecitabine 1700-2000mg/m2/day on days1-14 every 21 days, 6 cycles.Capecitabine is to be continued until disease progression or intolerable toxicity.; Other Names: Xeloda
Experimental: H-B: ERCC1 High Expression Group B; DX：Docetaxel+Capecitabine	Drug: Docetaxel+Capecitabine; Docetaxel 75mg/m2, d1; Capecitabine 1700-2000mg/m2/day on days1-14 every 21 days, 6 cycles. Capecitabine is to be continued until disease progression or intolerable toxicity.; Other Names: Xeloda; Docetaxel for injection
Active Comparator: L: ERCC1 Low Expression Group; XP：Capecitabine+Cisplatin	Drug: Capecitabine+Cisplatin; Cisplatin 75mg/m2, d1; Capecitabine 1700-2000mg/m2/day on days1-14 every 21 days, 6 cycles.Capecitabine is to be continued until disease progression or intolerable toxicity.; Other Names: Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-Free Survival (PFS)	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response	2 years
Overall Survival(OS)	2 years
Objective Response Rate(ORR),Including Complete Response(CR) and Partial Response(PR)	2 years
Disease Control Rate(DCR), Including Complete Response(CR) , Partial Response(PR) and Stable Disease(SD)	2 years
Safety(number and degree of adverse events)	2 years
Quality of Life(QOL)	2 years

Collaborators and Investigators

• Sponsor: China Medical University, China
• Investigators: Principal Investigator: Yunpeng Liu, MD., PhD, China Medical University, China; Principal Investigator: Xiujuan Qu, MD.,PhD., China Medical University, China

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: October 15, 2013
• First Submitted That Met QC Criteria: October 18, 2013
• First Posted (Estimate): October 23, 2013

Study Record Updates

• Last Update Posted (Actual): May 30, 2019
• Last Update Submitted That Met QC Criteria: May 28, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Gastric Cancer; Platinum; Chemotherapy; ERCC1
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Capecitabine
• Other Study ID Numbers: CLOG1301