A Study of Avastin (Bevacizumab) in Combination With XELOX or FOLFOX-4 in Patients With Metastatic Colorectal Cancer.

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00349336
• Collaborator: (none)
• Enrollment: 64
• Locations: 7
• Arms: 2
• Duration (Months): 27
• Patients Per Site: 9.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This 2 arm study will compare the pharmacokinetics and safety of Avastin at steady state under 2 different dosing regimens, in combination with XELOX (oxaliplatin + Xeloda) or FOLFOX-4 (oxaliplatin, leucovorin and 5-fluorouracil). Patients randomized to the XELOX arm will receive Avastin (7.5mg/kg iv) on Day 1 of each 3 week cycle; patients randomized to the FOLFOX-4 arm will receive Avastin (5mg/kg iv) on Day 1 of each 2 week cycle. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: bevacizumab [Avastin]; Drug: XELOX; Drug: bevacizumab [Avastin]; Drug: FOLFOX-4	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open Label Trial to Assess the Steady State Pharmacokinetics of Avastin Given With Either XELOX or FOLFOX-4 in Patients With Metastatic Colorectal Cancer
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: bevacizumab [Avastin]; 7.5mg/kg iv on day 1 of each 3 week cycle; Drug: XELOX; As prescribed
Experimental: 2	Drug: bevacizumab [Avastin]; 5mg/kg iv on day 1 of each 2 week cycle; Drug: FOLFOX-4; As prescribed

Outcome Measures

Primary Outcome Measures

1. Weekly Steady-state Exposure of Bevacizumab [Up to 48 weeks]

   Area under the serum concentration-time curve per week, at steady state (AUCss per week). Estimation of the parameter was performed using non-compartmental methods.

Secondary Outcome Measures

1. Time Zero to Last Measurable Plasma Concentration of Bevacizumab [Up to 48 weeks]

   Area under the serum concentration-time curve from time zero to the time of the last measurable plasma concentration (AUC 0-last). Estimation of the parameter was performed using non-compartmental methods.

2. Steady-state Exposure of Bevacizumab From Time Zero to Tau [Up to 48 weeks]

   Area under the serum concentration-time curve from time zero to tau, at steady state (AUCss 0-tau), where tau was the length of the cycle, i.e., tau = 3 weeks for XELOX+BV and tau = 2 weeks for FOLFOX-4+BEV. Estimation of the parameter was performed using non-compartmental methods.

3. Maximum Serum Concentration of Bevacizumab at Steady State [Up to 48 weeks]

   Maximum serum concentration at steady state (Css,max). Estimation of the parameter was performed using non-compartmental methods.

4. Minimum Serum Concentration of Bevacizumab at Steady State [Up to 48 weeks]

   Minimum serum concentration at steady state (Css, min). Estimation of the parameter was performed using non-compartmental methods.

5. Serum Clearance of Bevacizumab [Up to 48 weeks]

   Serum clearance (CL). Estimation of the parameter was performed using non-compartmental methods.

6. Time of Maximum Serum Concentration of Bevacizumab [Up to 48 weeks]

   Time of maximum serum concentration (tmax). Estimation of the parameter was performed using non-compartmental methods.

7. Volume of Distribution of Bevacizumab at Steady State [Up to 48 weeks]

   Volume of distribution at steady state (Vss). Estimation of the parameter was performed using non-compartmental methods.

8. Terminal Half-life of Bevacizumab [Up to 48 weeks]

   Terminal half-life (t1/2) (apparent elimination half-life). Estimation of the parameter was performed using non-compartmental methods.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• adult patients, >=18 years of age;

• adenocarcinoma of the colon or rectum, with metastatic or locally advanced disease;

• =1 target lesion.

Exclusion Criteria:

• patients who have previously received systemic treatment for advanced or metastatic disease;

• patients who have received adjuvant treatment for non-metastatic disease in past 3 months;

• previous therapy with oxaliplatin or Avastin.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Box Hill		Australia	3128
2		Fitzroy		Australia	3065
3		Sydney		Australia	2031
4		Brampton	Ontario	Canada	L6R 3J7
5		Hamilton	Ontario	Canada	L8V 5C2
6		Toronto	Ontario	Canada	M5G 2M9
7		Christchurch		New Zealand

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: NCT00349336
• Other Study ID Numbers: NO20254
• First Posted: Jul 7, 2006
• Last Update Posted: Sep 18, 2012
• Last Verified: Sep 1, 2012

• Additional relevant MeSH terms: Colorectal Neoplasms; Bevacizumab

Study Results

Participant Flow

Recruitment Details	A total of 64 patients in 7 centers were enrolled between 01 August 2006 to 28 May 2008. 37 were included in the pharmacokinetic (PK) analyses.

Arm/Group Title	XELOX+Bevacizumab	FOLFOX-4+Bevacizumab
Arm/Group Description	XELOX regimen = oxaliplatin in combination with capecitabine. Bevacizumab 7.5 mg/kg IV followed by oxaliplatin 130 mg/m² IV on Day 1 in combination with capecitabine, administered orally at a dose of 1000 mg/m² twice daily (BID); 3-week cycles up to 48 weeks (Cycle 16).	FOLFOX-4 regimen = oxaliplatin in combination with infusional 5-fluorouracil and leucovorin. Bevacizumab 5.0 mg/kg IV followed by oxaliplatin 85 mg/m² IV on Day 1 concomitantly with leucovorin 200 mg/m² IV, followed by 5-fluorouracil administered as a 400 mg/m² bolus injection, and then as a 600 mg/m² continuous infusion on Days 1 and 2; 2-week cycles for up to 48 weeks (Cycle 24).
Period Title: Overall Study
STARTED	32	32
COMPLETED	19	18
NOT COMPLETED	13	14

Baseline Characteristics

Arm/Group Title	XELOX+Bevacizumab	FOLFOX-4+Bevacizumab	Total
Arm/Group Description	XELOX regimen = oxaliplatin in combination with capecitabine. Bevacizumab 7.5 mg/kg IV followed by oxaliplatin 130 mg/m² IV on Day 1 in combination with capecitabine, administered orally at a dose of 1000 mg/m² twice daily (BID); 3-week cycles up to 48 weeks (Cycle 16).	FOLFOX-4 regimen = oxaliplatin in combination with infusional 5-fluorouracil and leucovorin. Bevacizumab 5.0 mg/kg IV followed by oxaliplatin 85 mg/m² IV on Day 1 concomitantly with leucovorin 200 mg/m² IV, followed by 5-fluorouracil administered as a 400 mg/m² bolus injection, and then as a 600 mg/m² continuous infusion on Days 1 and 2; 2-week cycles for up to 48 weeks (Cycle 24).	Total of all reporting groups
Overall Participants	32	32	64
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.9 (12.56)	57.9 (10.84)	56.9 (11.74)
Sex: Female, Male (Count of Participants)
Female	13 40.6%	17 53.1%	30 46.9%
Male	19 59.4%	15 46.9%	34 53.1%

Outcome Measures

1. Secondary Outcome

Title	Time Zero to Last Measurable Plasma Concentration of Bevacizumab
Description	Area under the serum concentration-time curve from time zero to the time of the last measurable plasma concentration (AUC 0-last). Estimation of the parameter was performed using non-compartmental methods.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

42 patients participated in pharmacokinetic (PK) assessments and of those, 37 were included in the PK analysis. Two patients receiving XELOX+BV were not included in the PK analysis due to protocol violations.

Arm/Group Title	XELOX+Bevacizumab	FOLFOX-4+Bevacizumab
Arm/Group Description	XELOX regimen = oxaliplatin in combination with capecitabine. Bevacizumab 7.5 mg/kg IV followed by oxaliplatin 130 mg/m² IV on Day 1 in combination with capecitabine, administered orally at a dose of 1000 mg/m² twice daily (BID); 3-week cycles up to 48 weeks (Cycle 16).	FOLFOX-4 regimen = oxaliplatin in combination with infusional 5-fluorouracil and leucovorin. Bevacizumab 5.0 mg/kg IV followed by oxaliplatin 85 mg/m² IV on Day 1 concomitantly with leucovorin 200 mg/m² IV, followed by 5-fluorouracil administered as a 400 mg/m² bolus injection, and then as a 600 mg/m² continuous infusion on Days 1 and 2; 2-week cycles for up to 48 weeks (Cycle 24).
Measure Participants	19	18
Mean (Standard Deviation) [day*ug/mL]	2457.19 (359.5)	1709.8 (497.0)

2. Primary Outcome

Title	Weekly Steady-state Exposure of Bevacizumab
Description	Area under the serum concentration-time curve per week, at steady state (AUCss per week). Estimation of the parameter was performed using non-compartmental methods.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

42 patients participated in pharmacokinetic (PK) assessments and of those, 37 were included in the PK analysis. Two patients receiving XELOX+BV were not included in the PK analysis due to protocol violations.

Arm/Group Title	XELOX+Bevacizumab	FOLFOX-4+Bevacizumab
Arm/Group Description	XELOX regimen = oxaliplatin in combination with capecitabine. Bevacizumab 7.5 mg/kg IV followed by oxaliplatin 130 mg/m² IV on Day 1 in combination with capecitabine, administered orally at a dose of 1000 mg/m² twice daily (BID); 3-week cycles up to 48 weeks (Cycle 16).	FOLFOX-4 regimen = oxaliplatin in combination with infusional 5-fluorouracil and leucovorin. Bevacizumab 5.0 mg/kg IV followed by oxaliplatin 85 mg/m² IV on Day 1 concomitantly with leucovorin 200 mg/m² IV, followed by 5-fluorouracil administered as a 400 mg/m² bolus injection, and then as a 600 mg/m² continuous infusion on Days 1 and 2; 2-week cycles for up to 48 weeks (Cycle 24).
Measure Participants	19	18
Mean (Standard Deviation) [day*ug/mL]	4090.3 (1047.6)	4022.4 (1774.2)

3. Secondary Outcome

Title	Steady-state Exposure of Bevacizumab From Time Zero to Tau
Description	Area under the serum concentration-time curve from time zero to tau, at steady state (AUCss 0-tau), where tau was the length of the cycle, i.e., tau = 3 weeks for XELOX+BV and tau = 2 weeks for FOLFOX-4+BEV. Estimation of the parameter was performed using non-compartmental methods.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

42 patients participated in pharmacokinetic (PK) assessments and of those, 37 were included in the PK analysis. Two patients receiving XELOX+BV were not included in the PK analysis due to protocol violations.

Arm/Group Title	XELOX+Bevacizumab	FOLFOX-4+Bevacizumab
Arm/Group Description	XELOX regimen = oxaliplatin in combination with capecitabine. Bevacizumab 7.5 mg/kg IV followed by oxaliplatin 130 mg/m² IV on Day 1 in combination with capecitabine, administered orally at a dose of 1000 mg/m² twice daily (BID); 3-week cycles up to 48 weeks (Cycle 16).	FOLFOX-4 regimen = oxaliplatin in combination with infusional 5-fluorouracil and leucovorin. Bevacizumab 5.0 mg/kg IV followed by oxaliplatin 85 mg/m² IV on Day 1 concomitantly with leucovorin 200 mg/m² IV, followed by 5-fluorouracil administered as a 400 mg/m² bolus injection, and then as a 600 mg/m² continuous infusion on Days 1 and 2; 2-week cycles for up to 48 weeks (Cycle 24).
Measure Participants	19	18
Mean (Standard Deviation) [day*ug/mL]	2457.0 (360.6)	1758.4 (468.5)

4. Secondary Outcome

Title	Maximum Serum Concentration of Bevacizumab at Steady State
Description	Maximum serum concentration at steady state (Css,max). Estimation of the parameter was performed using non-compartmental methods.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

42 patients participated in pharmacokinetic (PK) assessments and of those, 37 were included in the PK analysis. Two patients receiving XELOX+BV were not included in the PK analysis due to protocol violations.

Arm/Group Title	XELOX+Bevacizumab	FOLFOX-4+Bevacizumab
Arm/Group Description	XELOX regimen = oxaliplatin in combination with capecitabine. Bevacizumab 7.5 mg/kg IV followed by oxaliplatin 130 mg/m² IV on Day 1 in combination with capecitabine, administered orally at a dose of 1000 mg/m² twice daily (BID); 3-week cycles up to 48 weeks (Cycle 16).	FOLFOX-4 regimen = oxaliplatin in combination with infusional 5-fluorouracil and leucovorin. Bevacizumab 5.0 mg/kg IV followed by oxaliplatin 85 mg/m² IV on Day 1 concomitantly with leucovorin 200 mg/m² IV, followed by 5-fluorouracil administered as a 400 mg/m² bolus injection, and then as a 600 mg/m² continuous infusion on Days 1 and 2; 2-week cycles for up to 48 weeks (Cycle 24).
Measure Participants	19	18
Mean (Standard Deviation) [ug/mL]	242 (31.6)	215.6 (53.2)

5. Secondary Outcome

Title	Minimum Serum Concentration of Bevacizumab at Steady State
Description	Minimum serum concentration at steady state (Css, min). Estimation of the parameter was performed using non-compartmental methods.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

42 patients participated in pharmacokinetic (PK) assessments and of those, 37 were included in the PK analysis. Two patients receiving XELOX+BV were not included in the PK analysis due to protocol violations.

Arm/Group Title	XELOX+Bevacizumab	FOLFOX-4+Bevacizumab
Arm/Group Description	XELOX regimen = oxaliplatin in combination with capecitabine. Bevacizumab 7.5 mg/kg IV followed by oxaliplatin 130 mg/m² IV on Day 1 in combination with capecitabine, administered orally at a dose of 1000 mg/m² twice daily (BID); 3-week cycles up to 48 weeks (Cycle 16).	FOLFOX-4 regimen = oxaliplatin in combination with infusional 5-fluorouracil and leucovorin. Bevacizumab 5.0 mg/kg IV followed by oxaliplatin 85 mg/m² IV on Day 1 concomitantly with leucovorin 200 mg/m² IV, followed by 5-fluorouracil administered as a 400 mg/m² bolus injection, and then as a 600 mg/m² continuous infusion on Days 1 and 2; 2-week cycles for up to 48 weeks (Cycle 24).
Measure Participants	19	18
Mean (Standard Deviation) [ug/ml]	59.6 (14.1)	80.0 (25.5)

6. Secondary Outcome

Title	Serum Clearance of Bevacizumab
Description	Serum clearance (CL). Estimation of the parameter was performed using non-compartmental methods.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

42 patients participated in pharmacokinetic (PK) assessments and of those, 37 were included in the PK analysis. Two patients receiving XELOX+BV were not included in the PK analysis due to protocol violations.

Arm/Group Title	XELOX+Bevacizumab	FOLFOX-4+Bevacizumab
Arm/Group Description	XELOX regimen = oxaliplatin in combination with capecitabine. Bevacizumab 7.5 mg/kg IV followed by oxaliplatin 130 mg/m² IV on Day 1 in combination with capecitabine, administered orally at a dose of 1000 mg/m² twice daily (BID); 3-week cycles up to 48 weeks (Cycle 16).	FOLFOX-4 regimen = oxaliplatin in combination with infusional 5-fluorouracil and leucovorin. Bevacizumab 5.0 mg/kg IV followed by oxaliplatin 85 mg/m² IV on Day 1 concomitantly with leucovorin 200 mg/m² IV, followed by 5-fluorouracil administered as a 400 mg/m² bolus injection, and then as a 600 mg/m² continuous infusion on Days 1 and 2; 2-week cycles for up to 48 weeks (Cycle 24).
Measure Participants	19	18
Mean (Standard Deviation) [L/day]	0.236 (0.051)	0.226 (0.056)

7. Secondary Outcome

Title	Time of Maximum Serum Concentration of Bevacizumab
Description	Time of maximum serum concentration (tmax). Estimation of the parameter was performed using non-compartmental methods.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

42 patients participated in pharmacokinetic (PK) assessments and of those, 37 were included in the PK analysis. Two patients receiving XELOX+BV were not included in the PK analysis due to protocol violations.

Arm/Group Title	XELOX+Bevacizumab	FOLFOX-4+Bevacizumab
Arm/Group Description	XELOX regimen = oxaliplatin in combination with capecitabine. Bevacizumab 7.5 mg/kg IV followed by oxaliplatin 130 mg/m² IV on Day 1 in combination with capecitabine, administered orally at a dose of 1000 mg/m² twice daily (BID); 3-week cycles up to 48 weeks (Cycle 16).	FOLFOX-4 regimen = oxaliplatin in combination with infusional 5-fluorouracil and leucovorin. Bevacizumab 5.0 mg/kg IV followed by oxaliplatin 85 mg/m² IV on Day 1 concomitantly with leucovorin 200 mg/m² IV, followed by 5-fluorouracil administered as a 400 mg/m² bolus injection, and then as a 600 mg/m² continuous infusion on Days 1 and 2; 2-week cycles for up to 48 weeks (Cycle 24).
Measure Participants	19	18
Mean (Standard Deviation) [hr]	6.442 (6.786)	4.958 (3.596)

8. Secondary Outcome

Title	Volume of Distribution of Bevacizumab at Steady State
Description	Volume of distribution at steady state (Vss). Estimation of the parameter was performed using non-compartmental methods.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

42 patients participated in pharmacokinetic (PK) assessments and of those, 37 were included in the PK analysis. Two patients receiving XELOX+BV were not included in the PK analysis due to protocol violations.

Arm/Group Title	XELOX+Bevacizumab	FOLFOX-4+Bevacizumab
Arm/Group Description	XELOX regimen = oxaliplatin in combination with capecitabine. Bevacizumab 7.5 mg/kg IV followed by oxaliplatin 130 mg/m² IV on Day 1 in combination with capecitabine, administered orally at a dose of 1000 mg/m² twice daily (BID); 3-week cycles up to 48 weeks (Cycle 16).	FOLFOX-4 regimen = oxaliplatin in combination with infusional 5-fluorouracil and leucovorin. Bevacizumab 5.0 mg/kg IV followed by oxaliplatin 85 mg/m² IV on Day 1 concomitantly with leucovorin 200 mg/m² IV, followed by 5-fluorouracil administered as a 400 mg/m² bolus injection, and then as a 600 mg/m² continuous infusion on Days 1 and 2; 2-week cycles for up to 48 weeks (Cycle 24).
Measure Participants	19	18
Mean (Standard Deviation) [L]	4.932 (1.409)	4.908 (1.563)

9. Secondary Outcome

Title	Terminal Half-life of Bevacizumab
Description	Terminal half-life (t1/2) (apparent elimination half-life). Estimation of the parameter was performed using non-compartmental methods.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

42 patients participated in pharmacokinetic (PK) assessments and of those, 37 were included in the PK analysis. Two patients receiving XELOX+BV were not included in the PK analysis due to protocol violations.

Arm/Group Title	XELOX+Bevacizumab	FOLFOX-4+Bevacizumab
Arm/Group Description	XELOX regimen = oxaliplatin in combination with capecitabine. Bevacizumab 7.5 mg/kg IV followed by oxaliplatin 130 mg/m² IV on Day 1 in combination with capecitabine, administered orally at a dose of 1000 mg/m² twice daily (BID); 3-week cycles up to 48 weeks (Cycle 16).	FOLFOX-4 regimen = oxaliplatin in combination with infusional 5-fluorouracil and leucovorin. Bevacizumab 5.0 mg/kg IV followed by oxaliplatin 85 mg/m² IV on Day 1 concomitantly with leucovorin 200 mg/m² IV, followed by 5-fluorouracil administered as a 400 mg/m² bolus injection, and then as a 600 mg/m² continuous infusion on Days 1 and 2; 2-week cycles for up to 48 weeks (Cycle 24).
Measure Participants	19	18
Mean (Standard Deviation) [hr]	381.2 (91.7)	394.1 (121.8)

Adverse Events

Arm/Group Title	XELOX+Bevacizumab		FOLFOX-4+Bevacizumab
Arm/Group Description	XELOX regimen = oxaliplatin in combination with capecitabine. Bevacizumab 7.5 mg/kg IV followed by oxaliplatin 130 mg/m² IV on Day 1 in combination with capecitabine, administered orally at a dose of 1000 mg/m² twice daily (BID); 3-week cycles up to 48 weeks (Cycle 16).		FOLFOX-4 regimen = oxaliplatin in combination with infusional 5-fluorouracil and leucovorin. Bevacizumab 5.0 mg/kg IV followed by oxaliplatin 85 mg/m² IV on Day 1 concomitantly with leucovorin 200 mg/m² IV, followed by 5-fluorouracil administered as a 400 mg/m² bolus injection, and then as a 600 mg/m² continuous infusion on Days 1 and 2; 2-week cycles for up to 48 weeks (Cycle 24).
All Cause Mortality
	XELOX+Bevacizumab		FOLFOX-4+Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	XELOX+Bevacizumab		FOLFOX-4+Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/32 (28.1%)		15/32 (46.9%)
Blood and lymphatic system disorders
Febrile Neutropenia	0/32 (0%)		1/32 (3.1%)
Iron Deficiency Anaemia	0/32 (0%)		1/32 (3.1%)
Gastrointestinal disorders
Diarrhoea	4/32 (12.5%)		1/32 (3.1%)
Abdominal Pain	0/32 (0%)		2/32 (6.3%)
Vomiting	1/32 (3.1%)		1/32 (3.1%)
Gastrointestinal Obstruction	0/32 (0%)		1/32 (3.1%)
Ileus	1/32 (3.1%)		0/32 (0%)
Nausea	0/32 (0%)		1/32 (3.1%)
Oesophagitis	1/32 (3.1%)		0/32 (0%)
Rectal Haemorhage	0/32 (0%)		1/32 (3.1%)
Small Intestinal Obstruction	0/32 (0%)		1/32 (3.1%)
Upper Gastrointestinal Haemorrhage	0/32 (0%)		1/32 (3.1%)
General disorders
Fatigue	0/32 (0%)		2/32 (6.3%)
Pyrexia	1/32 (3.1%)		1/32 (3.1%)
Catheter Thrombosis	0/32 (0%)		1/32 (3.1%)
Chest Pain	1/32 (3.1%)		0/32 (0%)
Hepatobiliary disorders
Bile Duct Obstruction	1/32 (3.1%)		0/32 (0%)
Cholecystitis	1/32 (3.1%)		0/32 (0%)
Immune system disorders
Hypersensitivity	0/32 (0%)		2/32 (6.3%)
Infections and infestations
Anorectal Infection	0/32 (0%)		1/32 (3.1%)
Infection	0/32 (0%)		1/32 (3.1%)
Sepsis	1/32 (3.1%)		0/32 (0%)
Injury, poisoning and procedural complications
Gastrointestinal Anastomotic Leak	0/32 (0%)		1/32 (3.1%)
Metabolism and nutrition disorders
Dehydration	2/32 (6.3%)		0/32 (0%)
Metabolic Acidosis	1/32 (3.1%)		0/32 (0%)
Vascular disorders
Haemorrhage	0/32 (0%)		1/32 (3.1%)
Other (Not Including Serious) Adverse Events
	XELOX+Bevacizumab		FOLFOX-4+Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/32 (100%)		32/32 (100%)
Blood and lymphatic system disorders
Neutropenia	4/32 (12.5%)		14/32 (43.8%)
Thrombocytopenia	1/32 (3.1%)		2/32 (6.3%)
Anaemia	0/32 (0%)		2/32 (6.3%)
Eye disorders
Eye Pain	3/32 (9.4%)		2/32 (6.3%)
Lacrimation Increased	0/32 (0%)		5/32 (15.6%)
Gastrointestinal disorders
Diarrhoea	20/32 (62.5%)		23/32 (71.9%)
Nausea	26/32 (81.3%)		16/32 (50%)
Abdominal Pain	11/32 (34.4%)		8/32 (25%)
Constipation	10/32 (31.3%)		9/32 (28.1%)
Vomiting	8/32 (25%)		9/32 (28.1%)
Stomatitis	5/32 (15.6%)		7/32 (21.9%)
Flatulence	9/32 (28.1%)		1/32 (3.1%)
Dyspepsia	4/32 (12.5%)		2/32 (6.3%)
Gastrooesophageal Reflux Disease	1/32 (3.1%)		5/32 (15.6%)
Haemorrhoids	3/32 (9.4%)		3/32 (9.4%)
Abdominal Distension	3/32 (9.4%)		2/32 (6.3%)
Abdominal Pain Lower	2/32 (6.3%)		3/32 (9.4%)
Abdominal Pain Upper	4/32 (12.5%)		1/32 (3.1%)
Rectal Haemorrhage	1/32 (3.1%)		4/32 (12.5%)
Abdominal Discomfort	2/32 (6.3%)		1/32 (3.1%)
Dry Mouth	1/32 (3.1%)		2/32 (6.3%)
Dysphagia	1/32 (3.1%)		2/32 (6.3%)
Oral Pain	1/32 (3.1%)		2/32 (6.3%)
Anal Fissure	0/32 (0%)		2/32 (6.3%)
Anorectal Discomfort	0/32 (0%)		2/32 (6.3%)
Gingival Bleeding	2/32 (6.3%)		0/32 (0%)
Hypoaesthesia Oral	0/32 (0%)		2/32 (6.3%)
Mouth Haemorrhage	0/32 (0%)		2/32 (6.3%)
Mouth Ulceration	0/32 (0%)		2/32 (6.3%)
General disorders
Fatigue	24/32 (75%)		23/32 (71.9%)
Temperature Intolerance	15/32 (46.9%)		12/32 (37.5%)
Mucosal Inflammation	6/32 (18.8%)		11/32 (34.4%)
Pyrexia	3/32 (9.4%)		7/32 (21.9%)
Oedema Peripheral	1/32 (3.1%)		6/32 (18.8%)
Influenza Like Illness	2/32 (6.3%)		3/32 (9.4%)
Injection Site Discolouration	3/32 (9.4%)		2/32 (6.3%)
Pain	3/32 (9.4%)		2/32 (6.3%)
Chest Pain	2/32 (6.3%)		2/32 (6.3%)
Chills	1/32 (3.1%)		2/32 (6.3%)
Mucosal Haemorrhage	2/32 (6.3%)		1/32 (3.1%)
Immune system disorders
Hypersensitivity	0/32 (0%)		4/32 (12.5%)
Infections and infestations
Rhinitis	5/32 (15.6%)		6/32 (18.8%)
Upper Respiratory Tract Infection	1/32 (3.1%)		4/32 (12.5%)
Nasopharyngitis	2/32 (6.3%)		2/32 (6.3%)
Oral Herpes	2/32 (6.3%)		2/32 (6.3%)
Urinary Tract Infection	1/32 (3.1%)		3/32 (9.4%)
Central Line Infection	0/32 (0%)		2/32 (6.3%)
Eye Infection	2/32 (6.3%)		0/32 (0%)
Lower Respiratory Tract Infection	0/32 (0%)		2/32 (6.3%)
Tooth Infection	0/32 (0%)		2/32 (6.3%)
Investigations
Weight Decreased	1/32 (3.1%)		5/32 (15.6%)
Gamma-Glutamyltransferase Increased	2/32 (6.3%)		1/32 (3.1%)
Metabolism and nutrition disorders
Anorexia	16/32 (50%)		8/32 (25%)
Decrease Appetite	2/32 (6.3%)		4/32 (12.5%)
Hyperglycaemia	2/32 (6.3%)		1/32 (3.1%)
Hypokalaemia	0/32 (0%)		2/32 (6.3%)
Musculoskeletal and connective tissue disorders
Pain in Extremity	7/32 (21.9%)		5/32 (15.6%)
Arthralgia	4/32 (12.5%)		7/32 (21.9%)
Back Pain	3/32 (9.4%)		6/32 (18.8%)
Musculoskeletal Pain	5/32 (15.6%)		4/32 (12.5%)
Musculoskeletal Chest Pain	1/32 (3.1%)		4/32 (12.5%)
Myalgia	2/32 (6.3%)		2/32 (6.3%)
Pain in Jaw	1/32 (3.1%)		3/32 (9.4%)
Groin Pain	2/32 (6.3%)		1/32 (3.1%)
Muscle Spasms	2/32 (6.3%)		1/32 (3.1%)
Neck Pain	1/32 (3.1%)		2/32 (6.3%)
Joint Stiffness	2/32 (6.3%)		0/32 (0%)
Muscle Twitching	0/32 (0%)		2/32 (6.3%)
Muscular Weakness	2/32 (6.3%)		0/32 (0%)
Musculoskeletal Stiffness	2/32 (6.3%)		0/32 (0%)
Nervous system disorders
Peripheral Sensory Neuropathy	15/32 (46.9%)		16/32 (50%)
Neuropathy Peripheral	15/32 (46.9%)		15/32 (46.9%)
Headache	10/32 (31.3%)		10/32 (31.3%)
Dizziness	6/32 (18.8%)		6/32 (18.8%)
Paraesthesia	4/32 (12.5%)		7/32 (21.9%)
Dysgeusia	3/32 (9.4%)		4/32 (12.5%)
Dysaesthesia	1/32 (3.1%)		2/32 (6.3%)
Cranial Neuropathy	2/32 (6.3%)		0/32 (0%)
Disturbance in Attention	0/32 (0%)		2/32 (6.3%)
Hypoaesthesia	0/32 (0%)		2/32 (6.3%)
Syncope	0/32 (0%)		2/32 (6.3%)
Psychiatric disorders
Insomnia	9/32 (28.1%)		9/32 (28.1%)
Renal and urinary disorders
Proteinuria	1/32 (3.1%)		3/32 (9.4%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	7/32 (21.9%)		13/32 (40.6%)
Cough	7/32 (21.9%)		8/32 (25%)
Pharyngolaryngeal Pain	3/32 (9.4%)		7/32 (21.9%)
Dysphonia	6/32 (18.8%)		3/32 (9.4%)
Dyspnoea	1/32 (3.1%)		6/32 (18.8%)
Rhinorrhoea	6/32 (18.8%)		1/32 (3.1%)
Nasal Congestion	3/32 (9.4%)		2/32 (6.3%)
Hiccups	1/32 (3.1%)		2/32 (6.3%)
Nasal Ulcer	0/32 (0%)		2/32 (6.3%)
Pulmonary Embolism	0/32 (0%)		2/32 (6.3%)
Respiratory Tract Congestion	2/32 (6.3%)		0/32 (0%)
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome	18/32 (56.3%)		1/32 (3.1%)
Alopecia	7/32 (21.9%)		9/32 (28.1%)
Skin Hyperpigmentation	7/32 (21.9%)		7/32 (21.9%)
Pruritis	3/32 (9.4%)		3/32 (9.4%)
Dermatitis Acneiform	4/32 (12.5%)		1/32 (3.1%)
Nail Disorder	4/32 (12.5%)		1/32 (3.1%)
Rash	3/32 (9.4%)		2/32 (6.3%)
Skin Discolouration	3/32 (9.4%)		2/32 (6.3%)
Dry Skin	3/32 (9.4%)		1/32 (3.1%)
Skin Fissures	2/32 (6.3%)		1/32 (3.1%)
Erythema	0/32 (0%)		2/32 (6.3%)
Hyperhidrosis	2/32 (6.3%)		0/32 (0%)
Vascular disorders
Hypertension	7/32 (21.9%)		7/32 (21.9%)
Thrombosis	1/32 (3.1%)		4/32 (12.5%)
Flushing	0/32 (0%)		3/32 (9.4%)
Hot Flush	0/32 (0%)		3/32 (9.4%)

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.