Trial Outcomes & Findings for A Study of Bevacizumab and Modified FOLFOX-6 (mFOLFOX-6) in Participants With Metastatic Colorectal Cancer (NCT NCT01383707)
NCT ID: NCT01383707
Last Updated: 2017-06-14
Results Overview
ORR was defined as the percentage of participants with shrinkage (partial response \[PR\]) or disappearance of cancer (complete response \[CR\]). Tumor response was evaluated according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). The same method of tumor measurement and assessment had to be used to characterize each lesion throughout the study. Tumor assessment consisted of computerized tomography (CT) scan (abdomen + pelvis + chest) or contrast-enhanced magnetic resonance imaging (CE-MRI) (abdomen + pelvis) + non CE-CT (chest) according to the choice of the center. CR, Disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
77 participants
Primary outcome timeframe
Up to 11 cycles of treatment (up to Week 22)
Results posted on
2017-06-14
Participant Flow
Participant milestones
| Measure |
Bevacizumab + Modified FOLFOX-6 (mFOLFOX-6)
Combination therapy of bevacizumab and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\], oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). 5-FU: 400 mg/meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours; Bevacizumab: 5 mg/kg IV on Day 1 of each 2 weeks' cycle; Levofolinic acid: 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle; Oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle
|
|---|---|
|
Overall Study
STARTED
|
77
|
|
Overall Study
COMPLETED
|
5
|
|
Overall Study
NOT COMPLETED
|
72
|
Reasons for withdrawal
| Measure |
Bevacizumab + Modified FOLFOX-6 (mFOLFOX-6)
Combination therapy of bevacizumab and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\], oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). 5-FU: 400 mg/meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours; Bevacizumab: 5 mg/kg IV on Day 1 of each 2 weeks' cycle; Levofolinic acid: 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle; Oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle
|
|---|---|
|
Overall Study
Consent withdrawal
|
6
|
|
Overall Study
Death
|
19
|
|
Overall Study
Other
|
8
|
|
Overall Study
Sponsor's decision
|
2
|
|
Overall Study
Adverse Event
|
14
|
|
Overall Study
Progressive disease
|
23
|
Baseline Characteristics
A Study of Bevacizumab and Modified FOLFOX-6 (mFOLFOX-6) in Participants With Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Bevacizumab + mFOLFOX-6
n=77 Participants
Combination therapy of bevacizumab and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\], oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). 5-FU: 400 mg/meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours; Bevacizumab: 5 mg/kg IV on Day 1 of each 2 weeks' cycle; Levofolinic acid: 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle; Oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle
|
|---|---|
|
Age, Continuous
|
63.7 years
STANDARD_DEVIATION 10.6 • n=99 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Up to 11 cycles of treatment (up to Week 22)Population: The ITT set, which included all enrolled participants, who received at least one dose of any study medication.
ORR was defined as the percentage of participants with shrinkage (partial response \[PR\]) or disappearance of cancer (complete response \[CR\]). Tumor response was evaluated according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). The same method of tumor measurement and assessment had to be used to characterize each lesion throughout the study. Tumor assessment consisted of computerized tomography (CT) scan (abdomen + pelvis + chest) or contrast-enhanced magnetic resonance imaging (CE-MRI) (abdomen + pelvis) + non CE-CT (chest) according to the choice of the center. CR, Disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Bevacizumab + mFOLFOX-6
n=77 Participants
Combination therapy of bevacizumab and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\], oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). 5-FU: 400 mg/meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours; Bevacizumab: 5 mg/kg IV on Day 1 of each 2 weeks' cycle; Levofolinic acid: 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle; Oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle
|
|---|---|
|
Objective Response Rate (ORR) in the Intent-to-treat (ITT) Analysis Set
|
54.5 percentage of participants
Interval 42.8 to 65.9
|
PRIMARY outcome
Timeframe: Up to 11 cycles of treatment (up to Week 22)Population: The PPAS included all subjects in the ITT set, who did not experience any major protocol violations.
ORR was defined as the percentage of participants with shrinkage (PR) or disappearance of cancer (CR). Tumor response was evaluated according to the RECIST v1.1. The same method of tumor measurement and assessment had to be used to characterize each lesion throughout the study. Tumor assessment consisted of CT scan (abdomen + pelvis + chest) or CE-MRI (abdomen + pelvis) + non CE-CT (chest) according to the choice of the center. CR, Disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.
Outcome measures
| Measure |
Bevacizumab + mFOLFOX-6
n=64 Participants
Combination therapy of bevacizumab and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\], oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). 5-FU: 400 mg/meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours; Bevacizumab: 5 mg/kg IV on Day 1 of each 2 weeks' cycle; Levofolinic acid: 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle; Oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle
|
|---|---|
|
Objective Response Rate (ORR) in the Per-protocol Analysis Set (PPAS)
|
64.1 percentage of participants
Interval 51.1 to 75.7
|
SECONDARY outcome
Timeframe: End of study up to approximately 3 yearsPopulation: The ITT set, which included all enrolled participants, who received at least one dose of any study medication.
The percentage of participants achieving R0/R1 liver resection was defined as the percentage of participants achieving R0 surgery (no residual tumor) plus percentage of participants achieving R1 surgery (surgical margin with microscopic residual tumor).
Outcome measures
| Measure |
Bevacizumab + mFOLFOX-6
n=77 Participants
Combination therapy of bevacizumab and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\], oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). 5-FU: 400 mg/meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours; Bevacizumab: 5 mg/kg IV on Day 1 of each 2 weeks' cycle; Levofolinic acid: 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle; Oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle
|
|---|---|
|
Percentage of Participants Achieving No Residual Tumor (R0)/Surgical Margin With Microscopic Residual Tumor (R1) Liver Resection
|
29.9 percentage of participants
Interval 20.0 to 41.4
|
SECONDARY outcome
Timeframe: End of study up to approximately 3 yearsPopulation: The ITT set, which included all enrolled participants, who received at least one dose of any study medication.
DFI was defined as the time from the date of R0/R1 surgery to the date of disease relapse or death due to any cause. Participants who did not progress were considered censored at the date of the last assessment performed. For participants receiving two-stage resection, the date of R0/R1 surgery was the date of the second surgery. Participants, who did not receive surgery and participants without R0/R1 surgery were censored at Day 1. DFI was calculated as follows: DFI (months) = (\[Date of R0/R1 surgery - Date of 1st relapse/Death\] + 1)/30
Outcome measures
| Measure |
Bevacizumab + mFOLFOX-6
n=77 Participants
Combination therapy of bevacizumab and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\], oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). 5-FU: 400 mg/meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours; Bevacizumab: 5 mg/kg IV on Day 1 of each 2 weeks' cycle; Levofolinic acid: 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle; Oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle
|
|---|---|
|
Disease-free Interval (DFI)
|
10.8 months
Interval 5.7 to 15.7
|
SECONDARY outcome
Timeframe: End of study up to approximately 3 yearsPopulation: The ITT set, which included all enrolled participants, who received at least one dose of any study medication.
PFS was defined as the time from the date of first study drug administration to the date of disease progression or death due to any cause, whichever came first. Progression was defined according to RECIST, v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions. Participants, who did not progress were censored at the date of the last assessment performed. Participants who withdrew from the study without documented progression and for whom an electronic case report form (eCRF) existed as evidence that evaluations had been made, were censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without post-baseline tumor assessments, but known to be alive were censored at the time of first study drug administration. PFS was calculated: PFS (months) = (\[Date of Event - Date of first study drug administration\] + 1)/30.
Outcome measures
| Measure |
Bevacizumab + mFOLFOX-6
n=77 Participants
Combination therapy of bevacizumab and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\], oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). 5-FU: 400 mg/meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours; Bevacizumab: 5 mg/kg IV on Day 1 of each 2 weeks' cycle; Levofolinic acid: 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle; Oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle
|
|---|---|
|
Progression-Free Survival (PFS)
|
11.7 months
Interval 10.3 to 14.3
|
SECONDARY outcome
Timeframe: End of study up to approximately 3 yearsPopulation: The ITT set, which included all enrolled participants, who received at least one dose of any study medication.
OS was defined as the time from the date of first study drug administration to the date of death due to any cause. Participants who were alive at the time of the analysis were censored at the last date the participant was known to be alive. OS was calculated as follows: OS (months) = (\[Date of Death - first study drug administration\] + 1)/30
Outcome measures
| Measure |
Bevacizumab + mFOLFOX-6
n=77 Participants
Combination therapy of bevacizumab and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\], oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). 5-FU: 400 mg/meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours; Bevacizumab: 5 mg/kg IV on Day 1 of each 2 weeks' cycle; Levofolinic acid: 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle; Oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle
|
|---|---|
|
Overall Survival (OS)
|
NA months
The median overall survival time and its 95% confidence interval were not estimable because of the low number of events (less than 50%) and of the distribution of censored participants over time.
|
Adverse Events
Bevacizumab + mFOLFOX-6
Serious events: 32 serious events
Other events: 77 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bevacizumab + mFOLFOX-6
n=77 participants at risk
Combination therapy of bevacizumab and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\], oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). 5-FU: 400 mg/meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours; Bevacizumab: 5 mg/kg IV on Day 1 of each 2 weeks' cycle; Levofolinic acid: 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle; Oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.6%
2/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Cardiac disorders
Acute myocardial infarction
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Cardiac disorders
Atrial fibrillation
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Cardiac disorders
Cardiac arrest
|
3.9%
3/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Cardiac disorders
Cardiac failure acute
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Abdominal pain
|
2.6%
2/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Constipation
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Diarrhoea
|
2.6%
2/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Vomiting
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
General disorders
Pyrexia
|
2.6%
2/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Hepatobiliary disorders
Biliary tract disorder
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Hepatobiliary disorders
Biloma
|
2.6%
2/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Hepatobiliary disorders
Hepatic failure
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Infections and infestations
Subcutaneous abscess
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Infections and infestations
Device related infection
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Injury, poisoning and procedural complications
Chemical peritonitis
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Investigations
Neutrophil count decreased
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Metabolism and nutrition disorders
Dehydration
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Musculoskeletal and connective tissue disorders
Fistula
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Nervous system disorders
Transient ischaemic attack
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
2.6%
2/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
3.9%
3/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Surgical and medical procedures
Biliary drainage
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Surgical and medical procedures
Colectomy
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Vascular disorders
Deep vein thrombosis
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Vascular disorders
Haemorrhage
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Vascular disorders
Hypertension
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Vascular disorders
Hypertensive crisis
|
1.3%
1/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
Other adverse events
| Measure |
Bevacizumab + mFOLFOX-6
n=77 participants at risk
Combination therapy of bevacizumab and mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil \[5-FU\], oxaliplatin) on Day 1 of every 2 weeks' cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability will undergo a liver metastasectomy. Thereafter participants will receive combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). 5-FU: 400 mg/meter-squared (mg/m\^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m\^2, continuous infusion over 46 hours; Bevacizumab: 5 mg/kg IV on Day 1 of each 2 weeks' cycle; Levofolinic acid: 200 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle; Oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
10.4%
8/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Blood and lymphatic system disorders
Leukopenia
|
10.4%
8/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Blood and lymphatic system disorders
Neutropenia
|
41.6%
32/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
13.0%
10/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Abdominal pain
|
14.3%
11/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
11.7%
9/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Constipation
|
19.5%
15/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Diarrhoea
|
22.1%
17/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.2%
4/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Nausea
|
50.6%
39/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Stomatitis
|
18.2%
14/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Vomiting
|
16.9%
13/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
General disorders
Asthenia
|
41.6%
32/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
General disorders
Fatigue
|
10.4%
8/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
General disorders
Mucosal inflammation
|
11.7%
9/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
General disorders
Pyrexia
|
20.8%
16/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
10.4%
8/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Nervous system disorders
Neuropathy peripheral
|
5.2%
4/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Nervous system disorders
Neurotoxicity
|
5.2%
4/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Nervous system disorders
Paraesthesia
|
57.1%
44/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.1%
7/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
18.2%
14/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.2%
4/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
6.5%
5/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Vascular disorders
Hypertension
|
39.0%
30/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Gastrointestinal disorders
Dyspepsia
|
5.2%
4/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Investigations
White blood cell count decreased
|
5.2%
4/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.2%
4/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Nervous system disorders
Headache
|
7.8%
6/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Renal and urinary disorders
Proteinuria
|
6.5%
5/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.2%
4/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.2%
4/77 • End of study up to approximately 3 years.
The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
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