Bevacizumab Therapy Untreated Unresectable Liver Metastases From Colorectal Cancer

LIAONING CANCER HOSPITAL&INSTITUTE

A multi-center, non-random, open study ,to observe efficacy and safety of bevacizumab plus Oxaliplatin based multidrug chemotherapy as conversion therapy for patients with previously untreated unresectable liver metastases from colorectal cancer.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Liver Metastases
• Intervention / Treatment: Drug: bevacizumab plus chemotherapy

Detailed Description

PRIMARY OBJECTIVES：To assess the objective response rate(ORR)（8 weeks after chemotherapy）

SECONDARY OBJECTIVES：

1. To assess the R0 resection rate of liver metastases（8 weeks after chemotherapy、every three months follow-up 1 time in R0 postoperative 1-2 years、Every six months follow-up 1 time in R0 postoperative 2-5 years）
2. To assess the incidence of adverse events of level 3-4 （Bleeding、Gastrointestinal Perforation、Anastomotic Fistula、Hypertension、Wound Healing Delay）（8 weeks after chemotherapy）

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150086
      • Second Affiliated Hosptial of Harbin Medical University
  • Liaoning
    • Shenyang, Liaoning, China
      • LiaoNing Cancer Hospital&Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written inform consent form
2. histologically or cytologically confirmed Colorectal Adenocarcinoma
3. Age≥18 and ≤80 years old
4. Primary colorectal cancer and liver metastases，Liver lesions determined to be unresectable by multidisciplinary team (MDT) （primary lesions surgically removed）
5. Simultaneity or heterochrony metastases
6. Colorectal cancer lesions from anal edge at least 8 cm
7. Within 6 months did not receive any chemotherapy, including targeted therapy
8. One or more measurable lesions, conventional Computed Tomography(CT) scanning measurement diameter at least 20 mm [Response Evaluation Criteria In Solid Tumors(RECIST) standard]
9. Eastern Collaborative Oncology Group(ECOG) 0 or 1
10. Expected lifetime at least for 12 weeks
11. Screening within 7 days， the ability of bone marrow, liver and kidney function reserve enough；Absolute neutrophil count（ANC）≥1.5x109/L; hemoglobin≥9.0g/dl; platelet count≥80 x109/L; Total Bilirubin(TBil)≤1.5 x upper level of normal range(ULN); Alanine Aminotransferase(ALT) and Aspartate Aminotransferase(AST)≤2.5 x ULN(Patients with hepatic metastasis≤5x ULN); alkaline phosphatase≤4 x ULN; serum creatinine≤1.5 x ULN;
12. Women of reproductive age should take effective contraceptive measures;

Exclusion Criteria:

1. Arrhythmia requiring medication（except β- receptor blocking pharmacon and digoxigenin），symptomatic coronary artery disease and myocardial ischemia [myocardial infarction (≤6months before enrollment)]，congestive heart failure [≥New York Heart Association(NYHA)2];
2. History of HIV infection,Chronic hepatitis B or hepatitis C of active phase(high copy virus DNA);
3. Other activated serious infection [>National Cancer Institute-Common Toxicity Criteria(NCI-CTC) 3.0];
4. Any extrahepatic metastases;
5. Seizures requiring medication(such as steroids or antiepileptic therapy);
6. Other malignancies in the past 5 years (except curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix);
7. Chronic inflammatory bowel disease, intestinal obstruction;
8. Drug abuse and medicine, psychology or social conditions may interfere with patients to participate in research or the results of the evaluation have influence;
9. Known or suspected allergy to any investigational drug in this study;
10. Any unstable condition or is likely to endanger the patient safety and compliance situation;
11. Pregnant or lactating women not using or refusing to use effective non hormonal means of contraception;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Bevacizumab plus chemotherapy; Bevacizumab:7.5mg/kg, iv, on day 1 of each 21 day cycle or 5mg/kg, iv, on day 1 of each 14 day cycle;; Oxaliplatin+capecitabine(XELOX):( The total dose not less than 70% of the recommended dose of this standard) Oxaliplatin: 130mg/m2,d1; capecitabine: 850-1,000mg/m2，d1-d14, bid，each 21 day cycle;; Oxaliplatin+5-Fluorouracil+ Levomisole（FOLFOX）: Oxaliplatin: 85mg/m2,iv for 2 hours ,d1; Levomisole（LV）: 400mg/m2,iv for 2 hours,d1; 5-Fluorouracil（5-FU） :400mg/m2 iv,d1,then 1200mg/m2/d ×2d continuous intravenous infusion(volume dose:2400mg/m2,iv for 46-48 hours ) each 14 day cycle;

Drug: bevacizumab plus chemotherapy; Bevacizumab:7.5mg/kg, iv, on day 1 of each 21 day cycle or 5mg/kg, iv, on day 1 of each 14 day cycle;; Oxaliplatin+capecitabine(XELOX):( The total dose not less than 70% of the recommended dose of this standard) Oxaliplatin: 130mg/m2,d1; capecitabine: 850-1,000mg/m2，d1-d14, bid，each 21 day cycle;; Oxaliplatin+5-Fluorouracil+ Levomisole（FOLFOX）: Oxaliplatin: 85mg/m2,iv for 2 hours ,d1; Levomisole（LV）: 400mg/m2,iv for 2 hours,d1; 5-Fluorouracil（5-FU） :400mg/m2 iv,d1,then 1200mg/m2/d ×2d continuous intravenous infusion(volume dose:2400mg/m2,iv for 46-48 hours ) each 14 day cycle;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the objective response rate(ORR)	8 weeks after chemotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the R0 resection rate of liver metastases	8 weeks after chemotherapy、every three months follow-up 1 time in R0 postoperative 1-2 years、Every six months follow-up 1 time in R0 postoperative 2-5 years

Other Outcome Measures

Outcome Measure	Time Frame
To assess the incidence of adverse events of level 3-4 （Bleeding、Gastrointestinal Perforation、Anastomotic Fistula、Hypertension、Wound Healing Delay）	8 weeks after chemotherapy

Collaborators and Investigators

• Sponsor: Liaoning Tumor Hospital & Institute
• Investigators: Principal Investigator: Chun Song, Ph.D, Professor

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Anticipated): May 1, 2013
• Study Completion (Anticipated): September 1, 2014

Study Registration Dates

• First Submitted: December 28, 2012
• First Submitted That Met QC Criteria: January 5, 2013
• First Posted (Estimate): January 8, 2013

Study Record Updates

• Last Update Posted (Estimate): January 29, 2013
• Last Update Submitted That Met QC Criteria: January 28, 2013
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: colorectal cancer; Bevacizumab; liver metastases; conversion therapy; objective response rate
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: Avastin Study