Bevacizumab Therapy Untreated Unresectable Liver Metastases From Colorectal Cancer

Sponsor

Liaoning Tumor Hospital & Institute (Other)

Overall Status

Unknown status

CT.gov ID

NCT01763450

Collaborator

(none)

100

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Metastases Colorectal Cancer	Drug: bevacizumab plus chemotherapy	Phase 2

Detailed Description

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

SECONDARY OBJECTIVES：

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）
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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

LIAONING CANCER HOSPITAL&INSTITUTE

Study Start Date :

Sep 1, 2012

Anticipated Primary Completion Date :

May 1, 2013

Anticipated Study Completion Date :

Sep 1, 2014

Arms and Interventions

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;

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

Outcome Measures

Primary Outcome Measures

To assess the objective response rate(ORR) [8 weeks after chemotherapy]

Secondary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Written inform consent form
histologically or cytologically confirmed Colorectal Adenocarcinoma
Age≥18 and ≤80 years old
Primary colorectal cancer and liver metastases，Liver lesions determined to be unresectable by multidisciplinary team (MDT) （primary lesions surgically removed）
Simultaneity or heterochrony metastases
Colorectal cancer lesions from anal edge at least 8 cm
Within 6 months did not receive any chemotherapy, including targeted therapy
One or more measurable lesions, conventional Computed Tomography(CT) scanning measurement diameter at least 20 mm [Response Evaluation Criteria In Solid Tumors(RECIST) standard]
Eastern Collaborative Oncology Group(ECOG) 0 or 1
Expected lifetime at least for 12 weeks
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;
Women of reproductive age should take effective contraceptive measures;

Exclusion Criteria:

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];
History of HIV infection,Chronic hepatitis B or hepatitis C of active phase(high copy virus DNA);
Other activated serious infection [>National Cancer Institute-Common Toxicity Criteria(NCI-CTC) 3.0];
Any extrahepatic metastases;
Seizures requiring medication(such as steroids or antiepileptic therapy);
Other malignancies in the past 5 years (except curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix);
Chronic inflammatory bowel disease, intestinal obstruction;
Drug abuse and medicine, psychology or social conditions may interfere with patients to participate in research or the results of the evaluation have influence;
Known or suspected allergy to any investigational drug in this study;
Any unstable condition or is likely to endanger the patient safety and compliance situation;
Pregnant or lactating women not using or refusing to use effective non hormonal means of contraception;