An Observational Study of Bevacizumab in Combination With 5-FU-Based Chemotherapy in Chinese Participants With Metastatic Colorectal Cancer

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01319877
• Collaborator: (none)
• Enrollment: 609
• Locations: 24
• Duration (Months): 48
• Patients Per Site: 25.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This observational study will evaluate the safety and efficacy of Bevacizumab in combination with 5-Fluorouracil based chemotherapy as first-line and second-line therapy in Chinese participants with metastatic colorectal cancer. Data will be collected from each participant for up to 3 years.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer

Study Design

• Study Type: Observational
• Actual Enrollment: 609 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Multi-center Observational Study of Bevacizumab Plus 5-FU Based Chemotherapy as First Line and Second Line Treatment for Chinese Patients With Metastatic Colorectal Cancer (ML25391)
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
First Line Treatment Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.
Second Line Treatment Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Events [36 months]

   An adverse event (AE) is defined as any untoward medical occurrence in a participant after administration of a pharmaceutical product and which did not necessarily have a causal relationship with this treatment.

2. Percentage of Participants With Serious Adverse Events [36 months]

   A Serious Adverse Event (SAE) was any untoward medical occurrence that at any dose was fatal, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant, or required intervention to prevent one or other of the outcomes listed above.

3. Percentage of Participants With Adverse Events of Special Interest [36 months]

4. Percentage of Participants With Bevacizumab-Related Adverse Events [36 months]

5. Percentage of Participants With Bevacizumab-related Serious Adverse Events [36 months]

Secondary Outcome Measures

1. Percentage of Participants Achieving an Overall Response [36 months]

   Overall response was defined as complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, all non-target lesions, and no new lesions. PR: At least a 30% decrease in the sum of the diameters of target lesions, no progression in non-target lesions, and no new lesions.

2. Progression-free Survival [36 months]

   Progression-free-survival (PFS) was defined as the time from the date when the participant signed the informed consent form to the time of first documented disease progression or death, whichever occurred first.

3. One-year Progression-free Survival Rate [1 year]

   One year progression-free survival rate was defined as the percentage of participants who were free of progression or death from the date when the participant signed the informed consent form to one year.

4. One-year Survival Rate [1 year]

5. Percentage of Participants Achieving an Overall Response Per Kirsten Rat Sarcoma Viral (KRAS) Oncogene Subgroup [36 months]

   Overall response was defined as complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, all non-target lesions, and no new lesions. PR: At least a 30% decrease in the sum of the diameters of target lesions, no progression in non-target lesions, and no new lesions. Results are reported per participants' Kirsten Rat Sarcoma Viral (KRAS) oncogene subgroup.

6. One-year Progression-free Survival Rate Per KRAS Subgroup [1 year]

   One year progression-free survival rate was defined as the percentage of participants who were free of progression or death from the date when the participant signed the informed consent form to one year. Results are reported per participants' Kirsten Rat Sarcoma Viral (KRAS) oncogene subgroup.

7. One-year Survival Rate by the KRAS Subgroup [1 year]

8. Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup [Up to 36 Months]

   Overall response was defined as complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, all non-target lesions, and no new lesions. PR: At least a 30% decrease in the sum of the diameters of target lesions, no progression in non-target lesions, and no new lesions. Results are reported per participants' chemotherapy regimen subgroup.

9. One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup [1 year]

   One year progression-free survival rate was defined as the percentage of participants who were free of progression or death from the date when the participant signed the informed consent form to one year. Results are reported per participants' chemotherapy regimen subgroup.

10. One-year Survival Rate by the Chemotherapy Regimen Subgroup [1 year]

11. Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire [Up to 36 Months]

    Quality of life was assessed at baseline and every three months after treatment by the EORTC QLQ-C30 questionnaire. The possible score range was 0 to 100, with a higher score indicating better functioning.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult Chinese participants, >/= 18 years of age

• Histologically confirmed and previously untreated metastatic colorectal cancer

• Initiated on treatment with Bevacizumab (in combination with 5-FU based chemotherapy) according to locally approved Bevacizumab China package insert

• Documented participant with medical records

Exclusion Criteria:

• Recent history of serious hemorrhage or hemoptysis of >/= 1/2 teaspoon of red blood

• Proteinuria at baseline (>/=2 grams / 24 hours)

• Major surgical procedure within 28 days prior to study treatment start, not fully healed wounds

• Pregnant or lactating women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Beijing		China	100071
2		Beijing		China	100083
3		Changzhou		China	213003
4		Chengdu		China	610041
5		Fuzhou		China	350014
6		Guangzhou		China	510080
7		Guangzhou		China	510515
8		Guangzhou		China	510655
9		Hangzhou		China	310003
10		Hangzhou		China	310009
11		Hangzhou		China	310022
12		Harbin		China	150040
13		Jinan		China	250117
14		Nanjing		China	210009
15		Nanjing		China	210036
16		Nanjing		China
17		Nanning		China	530021
18		Shanghai		China	200003
19		Shanghai		China	200032
20		Shenyang		China	110001
21		Shenyang		China	110042
22		Wuhan		China	430079
23		Xi'an		China	710032
24		Xiamen		China	361004

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01319877
• Other Study ID Numbers: ML25391
• First Posted: Mar 22, 2011
• Last Update Posted: Sep 7, 2016
• Last Verified: Jul 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Colorectal Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	Three enrolled participants received third-line therapy and were not included in the evaluable population.

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Period Title: Overall Study
STARTED	453	153
COMPLETED	345	108
NOT COMPLETED	108	45

Baseline Characteristics

Arm/Group Title	First Line Treatment	Second Line Treatment	Total
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.	Total of all reporting groups
Overall Participants	453	153	606
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.7 (11.9)	54.5 (11.9)	55.4 (11.9)
Sex: Female, Male (Count of Participants)
Female	183 40.4%	53 34.6%	236 38.9%
Male	270 59.6%	100 65.4%	370 61.1%
Region of Enrollment (participants) [Number]
China	453 100%	153 100%	606 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Events
Description	An adverse event (AE) is defined as any untoward medical occurrence in a participant after administration of a pharmaceutical product and which did not necessarily have a causal relationship with this treatment.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
Number [percentage of participants]	76.4 16.9%	68.0 44.4%

2. Primary Outcome

Title	Percentage of Participants With Serious Adverse Events
Description	A Serious Adverse Event (SAE) was any untoward medical occurrence that at any dose was fatal, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant, or required intervention to prevent one or other of the outcomes listed above.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
Number [percentage of participants]	4.9 1.1%	4.6 3%

3. Primary Outcome

Title	Percentage of Participants With Adverse Events of Special Interest
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
Number [percentage of participants]	9.1 2%	5.9 3.9%

4. Primary Outcome

Title	Percentage of Participants With Bevacizumab-Related Adverse Events
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
Number [percentage of participants]	54.5 12%	45.8 29.9%

5. Primary Outcome

Title	Percentage of Participants With Bevacizumab-related Serious Adverse Events
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
Number [percentage of participants]	3.1 0.7%	2.0 1.3%

6. Secondary Outcome

Title	Percentage of Participants Achieving an Overall Response
Description	Overall response was defined as complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, all non-target lesions, and no new lesions. PR: At least a 30% decrease in the sum of the diameters of target lesions, no progression in non-target lesions, and no new lesions.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
Number (95% Confidence Interval) [percentage of participants]	21.0 4.6%	10.5 6.9%

7. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free-survival (PFS) was defined as the time from the date when the participant signed the informed consent form to the time of first documented disease progression or death, whichever occurred first.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
Median (95% Confidence Interval) [months]	9.1	8.1

8. Secondary Outcome

Title	One-year Progression-free Survival Rate
Description	One year progression-free survival rate was defined as the percentage of participants who were free of progression or death from the date when the participant signed the informed consent form to one year.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
Number (95% Confidence Interval) [percentage of participants]	34.2 7.5%	29.9 19.5%

9. Secondary Outcome

Title	One-year Survival Rate
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
Number (95% Confidence Interval) [percentage of participants]	68.7 15.2%	69.1 45.2%

10. Secondary Outcome

Title	Percentage of Participants Achieving an Overall Response Per Kirsten Rat Sarcoma Viral (KRAS) Oncogene Subgroup
Description	Overall response was defined as complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, all non-target lesions, and no new lesions. PR: At least a 30% decrease in the sum of the diameters of target lesions, no progression in non-target lesions, and no new lesions. Results are reported per participants' Kirsten Rat Sarcoma Viral (KRAS) oncogene subgroup.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

Participants with known KRAS status were evaluated.

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
Wild-type	18.6 4.1%	10.3 6.7%
Mutant-type	10.7 2.4%	4.8 3.1%

11. Secondary Outcome

Title	One-year Progression-free Survival Rate Per KRAS Subgroup
Description	One year progression-free survival rate was defined as the percentage of participants who were free of progression or death from the date when the participant signed the informed consent form to one year. Results are reported per participants' Kirsten Rat Sarcoma Viral (KRAS) oncogene subgroup.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Participants with known KRAS status were evaluated.

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
Wild-type	45.2 10%	31.3 20.5%
Mutant-type	19.5 4.3%	0 0%

12. Secondary Outcome

Title	One-year Survival Rate by the KRAS Subgroup
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Participants with known KRAS status were evaluated

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
Wild-type	81.0 17.9%	69.1 45.2%
Mutant-type	57.9 12.8%	33.9 22.2%

13. Secondary Outcome

Title	Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup
Description	Overall response was defined as complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, all non-target lesions, and no new lesions. PR: At least a 30% decrease in the sum of the diameters of target lesions, no progression in non-target lesions, and no new lesions. Results are reported per participants' chemotherapy regimen subgroup.
Time Frame	Up to 36 Months

Outcome Measure Data

Analysis Population Description

Participants with known prior chemotherapy regimens were evaluated

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
FOLFOX	25.7 5.7%	15.2 9.9%
IFL	18.5 4.1%	10.9 7.1%
XELIRI	45.5 10%	14.3 9.3%
XELOX	32.1 7.1%	0 0%
Others	5.8 1.3%	7.1 4.6%

14. Secondary Outcome

Title	One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup
Description	One year progression-free survival rate was defined as the percentage of participants who were free of progression or death from the date when the participant signed the informed consent form to one year. Results are reported per participants' chemotherapy regimen subgroup.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Participants with known prior chemotherapy regimens were evaluated.

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
FOLFOX	38.9 8.6%	38.1 24.9%
IFL	29.1 6.4%	32.2 21%
XELIRI	13.3 2.9%	20.0 13.1%
XELOX	44.9 9.9%	20.8 13.6%
Others	19.5 4.3%	16.7 10.9%

15. Secondary Outcome

Title	One-year Survival Rate by the Chemotherapy Regimen Subgroup
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Participants with known prior chemotherapy regimens were evaluated

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	453	153
FOLFOX	66.6 14.7%	71.6 46.8%
IFL	70.8 15.6%	71.4 46.7%
XELIRI	66.7 14.7%	20.8 13.6%
XELOX	75.2 16.6%	0 0%
Others	64.7 14.3%	60.0 39.2%

16. Secondary Outcome

Title	Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire
Description	Quality of life was assessed at baseline and every three months after treatment by the EORTC QLQ-C30 questionnaire. The possible score range was 0 to 100, with a higher score indicating better functioning.
Time Frame	Up to 36 Months

Outcome Measure Data

Analysis Population Description

Evaluable participants.

Arm/Group Title	First Line Treatment	Second Line Treatment
Arm/Group Description	Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy.	Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy.
Measure Participants	248	67
Baseline (n=248,67)	63.68 (18.020)	65.67 (14.103)
Visit 2 (n=159,44)	62.89 (15.875)	64.96 (17.105)
Visit 3 (n=80,21)	59.79 (18.073)	56.35 (19.168)
Visit 4 (n=50,12)	54.83 (22.718)	61.11 (14.360)
Visit 5 (n=26,9)	57.05 (15.758)	62.96 (16.724)
Visit 6 (n=15,5)	57.22 (14.389)	73.33 (16.030)
Visit 7 (n=11,4)	56.82 (16.168)	72.92 (15.773)
Visit 8 (n=7,3)	60.72 (14.205)	66.67 (8.335)
Visit 9 (n=4,1)	45.83 (15.960)	66.67 (NA)
Visit 10 (n=1,0)	50.00 (NA)	NA (NA)

Adverse Events

Time Frame	Up to 36 months
Arm/Group Title	First and Second Line Treatment
Arm/Group Description	The participants from the first line and second line treatments were combined for the adverse event analysis.
All Cause Mortality
	First and Second Line Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	First and Second Line Treatment
	Affected / at Risk (%)	# Events
Total	29/606 (4.8%)
Blood and lymphatic system disorders
Febrile neutropenia	1/606 (0.2%)
Bone marrow failure	1/606 (0.2%)
Cardiac disorders
Myocardial infarction	2/606 (0.3%)
Angina pectoris	1/606 (0.2%)
Gastrointestinal disorders
Enteritis	2/606 (0.3%)
Intestinal obstruction	2/606 (0.3%)
Intestinal perforation	2/606 (0.3%)
Gastritis	1/606 (0.2%)
Gastrointestinal hemorrhage	1/606 (0.2%)
Gastrointestinal perforation	1/606 (0.2%)
Mouth ulceration	1/606 (0.2%)
Large intestinal obstruction	1/606 (0.2%)
Enterovesical fistula	1/606 (0.2%)
General disorders
Pyrexia	2/606 (0.3%)
Infections and infestations
Infection	2/606 (0.3%)
Bacteremia	1/606 (0.2%)
Peritonitis	1/606 (0.2%)
Urinary tract infection	1/606 (0.2%)
Injury, poisoning and procedural complications
Urinary tract stoma complication	1/606 (0.2%)
Investigations
Neutrophil count decreased	2/606 (0.3%)
Nervous system disorders
Hypoxic-ischaemic encephalopathy	1/606 (0.2%)
Renal and urinary disorders
Ureteric fistula	1/606 (0.2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/606 (0.2%)
Vascular disorders
Deep vein thrombosis	4/606 (0.7%)
Other (Not Including Serious) Adverse Events
	First and Second Line Treatment
	Affected / at Risk (%)	# Events
Total	450/606 (74.3%)
Blood and lymphatic system disorders
Bone marrow failure	73/606 (12%)
Gastrointestinal disorders
Nausea	108/606 (17.8%)
Vomiting	93/606 (15.3%)
Diarrhea	65/606 (10.7%)
Constipation	31/606 (5.1%)
General disorders
Pyrexia	58/606 (9.6%)
Fatigue	52/606 (8.6%)
Investigations
White blood cell count decreased	130/606 (21.5%)
Neutrophil count decreased	100/606 (16.5%)
Platelet count decreased	39/606 (6.4%)
Alanine aminotransferase increased	37/606 (6.1%)
Aspartate aminotransferase increased	36/606 (5.9%)
Metabolism and nutrition disorders
Decreased appetite	50/606 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.