Clinical trial NCT01763450: Bevacizumab Therapy Untreated Unresectable Liver Metastases From Colorectal Cancer
Official title: LIAONING CANCER HOSPITAL&INSTITUTE
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Liver Metastases
Colorectal Cancer
Keywords: Bevacizumab
conversion therapy
liver metastases
colorectal cancer
objective response rate
Lead sponsor: Liaoning Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2013-01-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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）

Eligibility criteria: 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;

Primary outcomes:
measure: To assess the objective response rate(ORR)
timeFrame: 8 weeks after chemotherapy
Secondary outcomes:
measure: To assess the R0 resection rate of liver metastases
timeFrame: 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 outcomes:
measure: To assess the incidence of adverse events of level 3-4 （Bleeding、Gastrointestinal Perforation、Anastomotic Fistula、Hypertension、Wound Healing Delay）
timeFrame: 8 weeks after chemotherapy
Locations:
city: Harbin
country: China
facility: Second Affiliated Hosptial of Harbin Medical University
state: Heilongjiang
city: Shenyang
country: China
facility: Liaoning Cancer Hospital&Institute
state: Liaoning
Study officials:
affiliation: Professor
name: Chun Song, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: