Trial Outcomes & Findings for Bevacizumab Plus Capecitabine (Xeloda) in Patients With Untreated Metastatic Colorectal Cancer (NCT NCT00203411)
NCT ID: NCT00203411
Last Updated: 2017-02-06
Results Overview
Progression Free Survival (PFS)- the interval from the date of enrollment to the first documented date of disease progression, death due to cancer, or the last date of a definitive assessment (not an unknown assessment) at which the patient is known to be progression-free. If there is an unknown assessment, then (a) if the next subsequent definitive assessment is complete response (CR), partial response (PR), or stable disease (SD), the patient is considered to be progression-free at the date of the subsequent definitive assessment and PFS is calculated as above; (b) if the next subsequent definitive assessment is progressive disease (PD), the patient is considered to be a failure at the time of the (earliest) assessment of unknown preceding the documented disease progression (i.e. PFS is back-dated to the date of the unknown assessment) and (c) if there is no subsequent definitive assessment, PFS for the patient is considered to be a censored observation at the date
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
45 participants
Primary outcome timeframe
12 months
Results posted on
2017-02-06
Participant Flow
Dates of recruitment period: October 2005 to February 2009 Types of location: Academic medical oncology clinical and community medical oncology clinics
Participant milestones
| Measure |
Bevacizumab Plus Capecitabine
Bevacizumab 7.5 mg/kg every 3 weeks will be administered interavenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m\^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
Capecitabine (Xeloda): 1000mg/m2 administered orally twice daily for two weeks followed by one week rest period
Bevacizumab: 7.5 mg/kg IV will be administered every 3 weeks
|
|---|---|
|
Treatment Period
STARTED
|
45
|
|
Treatment Period
COMPLETED
|
45
|
|
Treatment Period
NOT COMPLETED
|
0
|
|
Follow-up
STARTED
|
45
|
|
Follow-up
COMPLETED
|
41
|
|
Follow-up
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Bevacizumab Plus Capecitabine
Bevacizumab 7.5 mg/kg every 3 weeks will be administered interavenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m\^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
Capecitabine (Xeloda): 1000mg/m2 administered orally twice daily for two weeks followed by one week rest period
Bevacizumab: 7.5 mg/kg IV will be administered every 3 weeks
|
|---|---|
|
Follow-up
Progressive Disease
|
4
|
Baseline Characteristics
Bevacizumab Plus Capecitabine (Xeloda) in Patients With Untreated Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Bevacizumab Plus Capecitabine
n=45 Participants
Bevacizumab 7.5 mg/kg every 3 weeks will be administered interavenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m\^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
|
|---|---|
|
Age, Continuous
|
79 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
36 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
45 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG)
Score of 1
|
17 subjects
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG)
Score of 2
|
28 subjects
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsProgression Free Survival (PFS)- the interval from the date of enrollment to the first documented date of disease progression, death due to cancer, or the last date of a definitive assessment (not an unknown assessment) at which the patient is known to be progression-free. If there is an unknown assessment, then (a) if the next subsequent definitive assessment is complete response (CR), partial response (PR), or stable disease (SD), the patient is considered to be progression-free at the date of the subsequent definitive assessment and PFS is calculated as above; (b) if the next subsequent definitive assessment is progressive disease (PD), the patient is considered to be a failure at the time of the (earliest) assessment of unknown preceding the documented disease progression (i.e. PFS is back-dated to the date of the unknown assessment) and (c) if there is no subsequent definitive assessment, PFS for the patient is considered to be a censored observation at the date
Outcome measures
| Measure |
Bevacizumab Plus Capecitabine
n=45 Participants
Bevacizumab 7.5 mg/kg every 3 weeks will be administered intravenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m\^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
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|---|---|
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Time to Disease Progression
|
6.87 months
Interval 5.1 to 11.5
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PRIMARY outcome
Timeframe: 3 monthsPopulation: all subjects that received chemotherapy
Number of Subjects that required Bevacizumab or Capecitabine dose modifications, delay, reduction or discontinuation due to adverse reactions.
Outcome measures
| Measure |
Bevacizumab Plus Capecitabine
n=45 Participants
Bevacizumab 7.5 mg/kg every 3 weeks will be administered intravenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m\^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
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|---|---|
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Number of Subjects Requiring Dose Modifications
Reduction of Capecitabine Dose
|
13 participants
|
|
Number of Subjects Requiring Dose Modifications
Discontinuation of Capecitabine
|
16 participants
|
|
Number of Subjects Requiring Dose Modifications
Delay in Bevacizumab Dose
|
15 participants
|
|
Number of Subjects Requiring Dose Modifications
Discontinuation of Bevacizumab
|
14 participants
|
|
Number of Subjects Requiring Dose Modifications
Delay in Capec itabineDose
|
8 participants
|
SECONDARY outcome
Timeframe: every 21 days up to 12 monthsEvaluation of target lesions Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Outcome measures
| Measure |
Bevacizumab Plus Capecitabine
n=45 Participants
Bevacizumab 7.5 mg/kg every 3 weeks will be administered intravenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m\^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
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|---|---|
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Response Rates
Complete Response
|
2 participants
|
|
Response Rates
Partial Response
|
14 participants
|
|
Response Rates
Stable Disease
|
16 participants
|
|
Response Rates
Progression
|
9 participants
|
|
Response Rates
Not Evaluable
|
4 participants
|
SECONDARY outcome
Timeframe: Baseline, Cycle 2, and End of StudyFunctional Assessment of Cancer Therapy-Colorectal (FACT-C) Trial Outcome Index (TOI) - a questionnaire assessing quality of life concerns pertinent to colorectal cancer patients. Questions address Physical, Emotional and Functional Well-Being. Scale: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), and very much (4). Higher numbers indicate a better state of well being. Scale 0 -136. Higher numbers indicating a better state of well-being. The Overall scores for the FACT-C Composite scale range between 0-100 with higher scores indicating a better state of well being. The EQ VAS= Euro Quality of Life 5 Dimension Self Reported Healthstate. It records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled 0 'Best imaginable health state' and 100 'Worst imaginable health state'.
Outcome measures
| Measure |
Bevacizumab Plus Capecitabine
n=45 Participants
Bevacizumab 7.5 mg/kg every 3 weeks will be administered intravenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m\^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
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|---|---|
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Quality of Life of Patients
Baseline FACT-C Trial outcome index (TOI)
|
62.85 score on a scale
Standard Deviation 12.12
|
|
Quality of Life of Patients
Cycle 2 FACT-C TOI
|
66.31 score on a scale
Standard Deviation 10.32
|
|
Quality of Life of Patients
End of Study FACT-C TOI
|
62.09 score on a scale
Standard Deviation 12.12
|
|
Quality of Life of Patients
Baseline FACT-C Composite
|
99.87 score on a scale
Standard Deviation 19.87
|
|
Quality of Life of Patients
Cycle 2 FACT-C Composite
|
105.38 score on a scale
Standard Deviation 17.02
|
|
Quality of Life of Patients
End of Study FACT-Composite
|
98.61 score on a scale
Standard Deviation 21.73
|
|
Quality of Life of Patients
Baseline EQ-5D VAS
|
61.76 score on a scale
Standard Deviation 23.17
|
|
Quality of Life of Patients
Cycle 2 EQ-5D VAS
|
68.59 score on a scale
Standard Deviation 22.26
|
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Quality of Life of Patients
End of Study EQ-5D VAS
|
66.54 score on a scale
Standard Deviation 23.18
|
Adverse Events
Bevacizumab Plus Capecitabine
Serious events: 45 serious events
Other events: 30 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bevacizumab Plus Capecitabine
n=45 participants at risk
Bevacizumab 7.5 mg/kg every 3 weeks will be administered intravenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m\^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
17.8%
8/45 • Number of events 8 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
General disorders
Fatigue
|
13.3%
6/45 • Number of events 6 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Skin and subcutaneous tissue disorders
Hand Foot Skin Reaction
|
13.3%
6/45 • Number of events 6 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Dehydration
|
8.9%
4/45 • Number of events 4 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
3/45 • Number of events 3 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Vascular disorders
Hypertension
|
6.7%
3/45 • Number of events 3 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Nausea
|
4.4%
2/45 • Number of events 2 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Mucositis
|
4.4%
2/45 • Number of events 2 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
General disorders
Pain-Abdomen
|
4.4%
2/45 • Number of events 2 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Anorexia
|
4.4%
2/45 • Number of events 2 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.2%
1/45 • Number of events 1 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Bloating
|
4.4%
2/45 • Number of events 2 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Nervous system disorders
Cerebral vascular accident
|
2.2%
1/45 • Number of events 1 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Vascular disorders
Deep vein thrombosis
|
2.2%
1/45 • Number of events 1 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Blood and lymphatic system disorders
Dyspepsia
|
2.2%
1/45 • Number of events 1 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Hemorrhage-GI
|
2.2%
1/45 • Number of events 1 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Obstruction
|
4.4%
2/45 • Number of events 2 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Hepatobiliary disorders
Liver Failure
|
2.2%
1/45 • Number of events 1 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Hepatobiliary disorders
Renal Failure
|
2.2%
1/45 • Number of events 1 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Infarction
|
2.2%
1/45 • Number of events 1 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
Other adverse events
| Measure |
Bevacizumab Plus Capecitabine
n=45 participants at risk
Bevacizumab 7.5 mg/kg every 3 weeks will be administered intravenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m\^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
|
|---|---|
|
General disorders
Fatigue
|
66.7%
30/45 • Number of events 30 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Diarrhea
|
62.2%
28/45 • Number of events 28 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Skin and subcutaneous tissue disorders
Hand Foot Skin Reaction
|
53.3%
24/45 • Number of events 24 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Nausea
|
46.7%
21/45 • Number of events 21 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Mucositis
|
35.6%
16/45 • Number of events 16 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Anorexia
|
33.3%
15/45 • Number of events 15 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Blood and lymphatic system disorders
Anemia
|
28.9%
13/45 • Number of events 13 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Nervous system disorders
Neuropathy
|
24.4%
11/45 • Number of events 11 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Nervous system disorders
Pain-Abdomen
|
22.2%
10/45 • Number of events 10 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Vascular disorders
Hypertension
|
22.2%
10/45 • Number of events 10 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
9/45 • Number of events 9 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
17.8%
8/45 • Number of events 8 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
17.8%
8/45 • Number of events 8 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.6%
7/45 • Number of events 7 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Blood and lymphatic system disorders
Leukopenia
|
15.6%
7/45 • Number of events 7 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Renal and urinary disorders
Proteinuria
|
15.6%
7/45 • Number of events 7 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Gastrointestinal disorders
Dehydration
|
15.6%
7/45 • Number of events 7 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Blood and lymphatic system disorders
Hemorrhage-Nose
|
13.3%
6/45 • Number of events 6 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Metabolism and nutrition disorders
Weight Loss
|
11.1%
5/45 • Number of events 5 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Nervous system disorders
Pain-Head
|
11.1%
5/45 • Number of events 5 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
General disorders
Memory Impairment
|
11.1%
5/45 • Number of events 5 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Ear and labyrinth disorders
Dizziness
|
11.1%
5/45 • Number of events 5 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
|
Blood and lymphatic system disorders
Edema-limb
|
11.1%
5/45 • Number of events 5 • From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place