Clinical trial NCT01695772: A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
Official title: A Multi-Center, Single-Arm, Pilot Study of 5-FU Based Doublet Chemotherapy Plus Bevacizumab as Neoadjuvant Therapy for Patients With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Colorectal Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-09-28
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This open-label, single arm, multicenter study evaluated the resection rate in participants with colorectal cancer and previously untreated unresectable liver-only metastases after adding bevacizumab to 5-FU based doublet chemotherapy in the neoadjuvant setting. Participants receive standard 5-FU based chemotherapy plus Avastin bevacizumab 5 milligrams per kilogram (mg/kg) every 2 weeks for a maximum of 12 cycles combined pre- and postoperatively, unless they experienced progressive disease or unacceptable toxicity.


Eligibility criteria: Inclusion Criteria:

* Adult Chinese participants, 18-75 years of age
* Histologically confirmed adenocarcinoma in colon or rectum with primary lesion surgically removed
* Previously untreated unresectable liver-only metastases
* Liver lesions determined to be unresectable by multidisciplinary team (MDT, consisting of experienced hepatic surgeons, medical oncologist and radiologist).
* No previous treatment against liver metastases, including chemotherapy, surgery, radiotherapy, Transarterial chemoembolisation therapy (TACE) and target therapy
* Adequate hematological, renal and hepatic function
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Life expectancy greater than (\>) 3 months

Exclusion Criteria:

* The relapse has occurred within 6 months of completion of the adjuvant treatment
* Expected impossible to achieve complete resection (R0 resection) and/or gain 30% residual liver volume even with responsive neoadjuvant therapy
* Participant cannot tolerate the surgery
* Other malignancies in the past 5 years, except for curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
* Any extrahepatic metastases and/or recurrence of the primary tumor
* Any residual toxicity from previous chemotherapy (except alopecia) of National Cancer Institute Common Toxicity Criteria (NCI CTC) v.4.0 grade 2
* Hypertension crisis or encephalopathy
* Pregnant or lactating women
* Clinically significant cardiovascular disease
* Evidence of bleeding diathesis or coagulopathy
* Current or recent (within 10 days of study drug initiation) use of full dose of aspirin, clopidrogel or warfarin
* History or evidence of Central Nervous System (CNS) disease (for example, primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke)

Primary outcomes:
measure: Percentage of Participants Achieving Complete Resection (R0 Resection)
timeFrame: At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)
Secondary outcomes:
measure: Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection)
timeFrame: At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)
measure: Percentage of Participants Achieving Objective Response
timeFrame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
measure: Number of Participants With Disease Progression or Relapse or Death
timeFrame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
measure: Progression Free Survival (PFS)
timeFrame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
measure: Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18
timeFrame: Months 3, 6, 9, 12, 15, and 18
measure: Number of Participants With Disease Relapse or Death
timeFrame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
measure: Disease Free Survival (DFS)
timeFrame: Complete resection date up to disease relapse or death until data cutoff on 12 May 2016 (up to approximately 3.5 years)
measure: Percent Probability Of Being Alive and Disease Free at Months 3, 6, 9, and 12
timeFrame: Months 3, 6, 9, and 12
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Guangzhou
country: China
facility: Sun Yet-sen University Cancer Center
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University College
city: Harbin
country: China
facility: The 2nd Affiliated Hospital of Harbin Medical University
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Shenyang
country: China
facility: Liaoning cancer Hospital & Institute
city: Wuhan
country: China
facility: Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: