Trial Outcomes & Findings for A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Colorectal Cancer (NCT NCT00700570)
NCT ID: NCT00700570
Last Updated: 2016-11-02
Results Overview
Participants were assessed via microscopic and macroscopic examination for tumor resectability after completion of 5 cycles of neoadjuvant treatment. Unresectable participants exhibited any of the following criteria: greater than or equal to (≥) 4 liver metastases; location and/or distribution of metastatic disease within the liver considered unsuitable for resection with clear margins; liver involvement precluding resection, in the setting of adequate parenchymal volume for otherwise viable liver function in the immediate postoperative period; and inability to maintain adequate circulation for viable liver function. Participants who had not met any of the above criteria at the end of 5 cycles underwent surgical resection. The percentage of participants with conversion from initially unresectable to resectable liver metastases was calculated as \[number of participants eligible for surgical resection divided by the number analyzed\] multiplied by 100.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
45 participants
Primary outcome timeframe
After 5 cycles of neoadjuvant treatment (10 weeks)
Results posted on
2016-11-02
Participant Flow
Participant milestones
| Measure |
Resected
Participants with unresectable liver metastases secondary to colorectal cancer (CRC) were assigned to receive neoadjuvant treatment of intravenous (IV) bevacizumab with oral (PO) capecitabine and IV oxaliplatin (XELOX). Bevacizumab was given as 5 milligrams per kilogram (mg/kg) on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 milligrams per meter-squared (mg/m\^2) on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Participants could be withdrawn at any point for unacceptable toxicity.
|
Unresected
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with partial response (PR) or stable disease (SD), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, repeated neoadjuvant treatment until documented resectability or progressive disease (PD). Participants could be withdrawn at any point for unacceptable toxicity.
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
26
|
|
Overall Study
COMPLETED
|
8
|
0
|
|
Overall Study
NOT COMPLETED
|
11
|
26
|
Reasons for withdrawal
| Measure |
Resected
Participants with unresectable liver metastases secondary to colorectal cancer (CRC) were assigned to receive neoadjuvant treatment of intravenous (IV) bevacizumab with oral (PO) capecitabine and IV oxaliplatin (XELOX). Bevacizumab was given as 5 milligrams per kilogram (mg/kg) on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 milligrams per meter-squared (mg/m\^2) on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Participants could be withdrawn at any point for unacceptable toxicity.
|
Unresected
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with partial response (PR) or stable disease (SD), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, repeated neoadjuvant treatment until documented resectability or progressive disease (PD). Participants could be withdrawn at any point for unacceptable toxicity.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
6
|
|
Overall Study
Discretion of Investigator or Sponsor
|
0
|
3
|
|
Overall Study
Disease Progression
|
8
|
11
|
|
Overall Study
Withdrawal by Subject
|
1
|
6
|
Baseline Characteristics
A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Resected
n=19 Participants
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Participants could be withdrawn at any point for unacceptable toxicity.
|
Unresected
n=26 Participants
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.0 years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
55.1 years
STANDARD_DEVIATION 10.4 • n=7 Participants
|
55.08 years
STANDARD_DEVIATION 11.2 • n=5 Participants
|
|
Gender
Female
|
6 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Gender
Male
|
13 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After 5 cycles of neoadjuvant treatment (10 weeks)Population: ITT Population.
Participants were assessed via microscopic and macroscopic examination for tumor resectability after completion of 5 cycles of neoadjuvant treatment. Unresectable participants exhibited any of the following criteria: greater than or equal to (≥) 4 liver metastases; location and/or distribution of metastatic disease within the liver considered unsuitable for resection with clear margins; liver involvement precluding resection, in the setting of adequate parenchymal volume for otherwise viable liver function in the immediate postoperative period; and inability to maintain adequate circulation for viable liver function. Participants who had not met any of the above criteria at the end of 5 cycles underwent surgical resection. The percentage of participants with conversion from initially unresectable to resectable liver metastases was calculated as \[number of participants eligible for surgical resection divided by the number analyzed\] multiplied by 100.
Outcome measures
| Measure |
All Participants
n=45 Participants
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
Unresected
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With Conversion From Unresectable to Resectable Liver Metastases
|
42.2 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, and within 4 weeks of end of treatment [EOT])Population: ITT Population.
Objective tumor response was assessed using RECIST version 1.1. Disease progression was defined as a ≥20 percent (%) increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. The percentage of participants with disease progression was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.
Outcome measures
| Measure |
All Participants
n=19 Participants
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
Unresected
n=26 Participants
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With Disease Progression
|
52.6 percentage of participants
|
46.2 percentage of participants
|
SECONDARY outcome
Timeframe: Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, and within 4 weeks of EOT)Population: ITT Population.
Objective tumor response was assessed using RECIST version 1.1. Disease progression was defined as a ≥20% increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. Time to disease progression was defined as the time from first dose to time of disease progression. Participants without progression were censored at the time of last tumor assessment. Time to disease progression was estimated using Kaplan-Meier analysis and expressed in months.
Outcome measures
| Measure |
All Participants
n=19 Participants
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
Unresected
n=26 Participants
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
|---|---|---|
|
Time to Disease Progression
|
10.1 months
Interval 7.0 to 20.4
|
8.7 months
Interval 5.0 to 14.2
|
SECONDARY outcome
Timeframe: Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, within 4 weeks of EOT, and at least 4 weeks after initial response)Population: ITT Population.
Objective tumor response was assessed using RECIST version 1.1. CR was defined as the disappearance of all target lesions, and PR was defined as a ≥30% decrease in the sum of longest diameters compared to Baseline. Response was confirmed at a minimum of 4 weeks after the first documented response. The percentage of participants with confirmed CR or PR was calculated as \[number of participants meeting the respective criteria divided by the number analyzed\] multiplied by 100.
Outcome measures
| Measure |
All Participants
n=19 Participants
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
Unresected
n=26 Participants
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants With a Best Overall Tumor Response of Complete Response (CR) or PR According to RECIST Version 1.1
|
47.4 percentage of participants
|
34.6 percentage of participants
|
SECONDARY outcome
Timeframe: Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, within 4 weeks of EOT, and at least 4 weeks after initial response)Population: ITT Population.
Objective tumor response was assessed using RECIST version 1.1. CR was defined as the disappearance of all target lesions, and PR was defined as a ≥30% decrease in the sum of longest diameters compared to Baseline. Response was to be confirmed at a minimum of 4 weeks after the first documented response. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, as well as no new target lesions. Disease progression or PD was defined as a ≥20% increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. Non-evaluability for tumor assessment was also documented when applicable. The percentage of participants with each level of response was calculated as \[number of participants meeting the respective criteria divided by the number analyzed\] multiplied by 100.
Outcome measures
| Measure |
All Participants
n=19 Participants
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
Unresected
n=26 Participants
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
|---|---|---|
|
Percentage of Participants by Best Overall Tumor Response According to RECIST Version 1.1
CR
|
36.8 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants by Best Overall Tumor Response According to RECIST Version 1.1
PR
|
10.5 percentage of participants
|
34.6 percentage of participants
|
|
Percentage of Participants by Best Overall Tumor Response According to RECIST Version 1.1
SD
|
0 percentage of participants
|
15.4 percentage of participants
|
|
Percentage of Participants by Best Overall Tumor Response According to RECIST Version 1.1
PD
|
52.6 percentage of participants
|
46.2 percentage of participants
|
|
Percentage of Participants by Best Overall Tumor Response According to RECIST Version 1.1
Non-evaluable
|
0 percentage of participants
|
3.8 percentage of participants
|
Adverse Events
All Participants
Serious events: 11 serious events
Other events: 45 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Participants
n=45 participants at risk
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
3/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Gastrointestinal disorders
Enteritis
|
2.2%
1/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
2.2%
1/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Gastrointestinal disorders
Ileus
|
4.4%
2/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
General disorders
Pyrexia
|
4.4%
2/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Infections and infestations
Enterocolitis infectious
|
2.2%
1/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Infections and infestations
Perihepatic abscess
|
2.2%
1/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Injury, poisoning and procedural complications
Intestinal anastomosis complication
|
2.2%
1/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
2.2%
1/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour associated fever
|
2.2%
1/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour necrosis
|
2.2%
1/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
Other adverse events
| Measure |
All Participants
n=45 participants at risk
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m\^2 on Day 1, and PO capecitabine as 1000 mg/m\^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
11.1%
5/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Blood and lymphatic system disorders
Leukopenia
|
13.3%
6/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Blood and lymphatic system disorders
Neutropenia
|
24.4%
11/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
42.2%
19/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Gastrointestinal disorders
Abdominal pain
|
17.8%
8/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Gastrointestinal disorders
Constipation
|
11.1%
5/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Gastrointestinal disorders
Diarrhoea
|
35.6%
16/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Gastrointestinal disorders
Nausea
|
31.1%
14/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Gastrointestinal disorders
Stomatitis
|
15.6%
7/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Gastrointestinal disorders
Vomiting
|
37.8%
17/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
General disorders
Fatigue
|
40.0%
18/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
General disorders
Mucosal inflammation
|
17.8%
8/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
General disorders
Pyrexia
|
17.8%
8/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Infections and infestations
Paronychia
|
6.7%
3/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Infections and infestations
Urinary tract infection
|
6.7%
3/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Investigations
Weight decreased
|
8.9%
4/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
44.4%
20/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Nervous system disorders
Dizziness
|
6.7%
3/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Nervous system disorders
Hypoaesthesia
|
6.7%
3/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Nervous system disorders
Neuropathy peripheral
|
42.2%
19/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
20.0%
9/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Psychiatric disorders
Insomnia
|
20.0%
9/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Renal and urinary disorders
Proteinuria
|
33.3%
15/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
8.9%
4/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
11.1%
5/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
77.8%
35/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Skin and subcutaneous tissue disorders
Pigmentation disorder
|
8.9%
4/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.9%
4/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
|
Vascular disorders
Hypertension
|
17.8%
8/45 • Up to approximately 3 years (continuously until 4 weeks after EOT)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER