Back to resultsA 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
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
5-FU based doublet chemotherapy
bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
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)
Sites / Locations
- Beijing Cancer Hospital
- Sun Yet-sen University Cancer Center
- The Second Affiliated Hospital of Zhejiang University College
- The 2nd Affiliated Hospital of Harbin Medical University
- Zhongshan Hospital Fudan University
- Liaoning cancer Hospital & Institute
- Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Bevacizumab
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Participants Achieving Complete Resection (R0 Resection)
R0 resection was defined as complete resection confirmed by pathology after pre-operative chemotherapy plus bevacizumab. Participants with R0 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.
Secondary Outcome Measures
Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection)
R1 resection was defined as achievement of incomplete tumor resection with microscopic involvement of a margin after pre-operative chemotherapy plus bevacizumab, as confirmed by pathology. Participants with R1 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.
Percentage of Participants Achieving Objective Response
Objective response rate was defined as the percentage of participants who achieved either Partial Response (PR) or Complete Response (CR) per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1. This is defined as the best response recorded from the start of trial treatment until disease progression (or death). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 mm). No new lesions. PR was defined as greater than or equal to [≥] 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Number of Participants With Disease Progression or Relapse or Death
According to RECIST v1.1 Progressive Disease is defined as a 20 % or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions.
Progression Free Survival (PFS)
Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. Kaplan-Meier curves were used to display PFS.
Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18
Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. The probability was estimated by Kaplan Meier curve analysis.
Number of Participants With Disease Relapse or Death
Disease Free Survival (DFS)
Disease Free Survival (DFS) was defined as the time from complete resection of liver metastases to disease relapse or death, for participants who achieve complete resection after pre-operative treatment with standard 5-FU based doublet regimen plus bevacizumab.
Percent Probability Of Being Alive and Disease Free at Months 3, 6, 9, and 12
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01695772
Brief Title
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
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
October 16, 2012 (Actual)
Primary Completion Date
April 4, 2015 (Actual)
Study Completion Date
May 12, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bevacizumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
5-FU based doublet chemotherapy
Intervention Description
Standard 5-FU based doublet chemotherapy. Protocol did not specify any particular chemotherapy regimen. The choice of 5-FU based doublet chemotherapy was as per standard of practice and the dosage of 5-FU based doublet chemotherapy was as per product labels.
Intervention Type
Drug
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
5 mg/kg every 2 weeks, up to 12 cycles pre- and postoperatively
Primary Outcome Measure Information:
Title
Percentage of Participants Achieving Complete Resection (R0 Resection)
Description
R0 resection was defined as complete resection confirmed by pathology after pre-operative chemotherapy plus bevacizumab. Participants with R0 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.
Time Frame
At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection)
Description
R1 resection was defined as achievement of incomplete tumor resection with microscopic involvement of a margin after pre-operative chemotherapy plus bevacizumab, as confirmed by pathology. Participants with R1 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.
Time Frame
At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)
Title
Percentage of Participants Achieving Objective Response
Description
Objective response rate was defined as the percentage of participants who achieved either Partial Response (PR) or Complete Response (CR) per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1. This is defined as the best response recorded from the start of trial treatment until disease progression (or death). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 mm). No new lesions. PR was defined as greater than or equal to [≥] 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time Frame
Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
Title
Number of Participants With Disease Progression or Relapse or Death
Description
According to RECIST v1.1 Progressive Disease is defined as a 20 % or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions.
Time Frame
Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
Title
Progression Free Survival (PFS)
Description
Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. Kaplan-Meier curves were used to display PFS.
Time Frame
Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
Title
Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18
Description
Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. The probability was estimated by Kaplan Meier curve analysis.
Time Frame
Months 3, 6, 9, 12, 15, and 18
Title
Number of Participants With Disease Relapse or Death
Time Frame
Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
Title
Disease Free Survival (DFS)
Description
Disease Free Survival (DFS) was defined as the time from complete resection of liver metastases to disease relapse or death, for participants who achieve complete resection after pre-operative treatment with standard 5-FU based doublet regimen plus bevacizumab.
Time Frame
Complete resection date up to disease relapse or death until data cutoff on 12 May 2016 (up to approximately 3.5 years)
Title
Percent Probability Of Being Alive and Disease Free at Months 3, 6, 9, and 12
Time Frame
Months 3, 6, 9, and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
ZIP/Postal Code
100142
Country
China
Facility Name
Sun Yet-sen University Cancer Center
City
Guangzhou
ZIP/Postal Code
510060
Country
China
Facility Name
The Second Affiliated Hospital of Zhejiang University College
City
Hangzhou
ZIP/Postal Code
310009
Country
China
Facility Name
The 2nd Affiliated Hospital of Harbin Medical University
City
Harbin
ZIP/Postal Code
150001
Country
China
Facility Name
Zhongshan Hospital Fudan University
City
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Liaoning cancer Hospital & Institute
City
Shenyang
ZIP/Postal Code
110042
Country
China
Facility Name
Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology
City
Wuhan
ZIP/Postal Code
430022
Country
China
12. IPD Sharing Statement
Learn more about this trial
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
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