A Study Comparing the Efficacy and Safety of Vanucizumab... | NCT02141295

ID	Type	Description	Link
2013-005108-32	EudraCT Number

Label	Type	Description	Intervention Names
Part 1 (Induction): Vanucizumab + mFOLFOX-6	Experimental	Participants will receive vanucizumab at a dose of 2000 milligram (mg) as intravenous (IV) infusion; oxaliplatin at a dose of 85 mg per meter-squared (mg/m^2) as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months).	Drug: 5-FU Drug: Folinic acid Drug: Oxaliplatin Drug: Vanucizumab
Part 1 (Maintenance): Vanucizumab + 5-FU + Folinic acid	Experimental	Participants will receive vanucizumab at a dose confirmed during induction as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.	Drug: 5-FU Drug: Folinic acid Drug: Vanucizumab
Part 2 (Induction): Bevacizumab + mFOLFOX-6	Active Comparator	Participants will receive bevacizumab at a dose of 5 milligram per kilogram (mg/kg) as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months).	Drug: 5-FU Drug: Bevacizumab Drug: Folinic acid Drug: Oxaliplatin
Part 2 (Induction): Vanucizumab + mFOLFOX-6

Name	Type	Description	Arm Group Labels	Other Names
5-FU	Drug	5-FU will be administered according to dose and schedule described in respective arm.	Part 1 (Induction): Vanucizumab + mFOLFOX-6 Part 1 (Maintenance): Vanucizumab + 5-FU + Folinic acid

Measure	Description	Time Frame
Progression-free Survival (PFS), Time to Event	Efficacy of vanucizumab was evaluated in terms of PFS as Investigator-Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). PFS was defined as the time between randomization and the date of first documented disease progression or death from any cause on study, whichever occurred first. Death on study was defined as death from any cause within 30 days of the last study treatment.	Baseline, every 8 weeks, up to approximately 29 months

Measure	Description	Time Frame
Percentage of Participants With Objective Response (ORR) as Assessed Using RECIST v. 1.1	Efficacy of vanucizumab was evaluated in terms of Percentage of Participants With ORR as Investigator-Assessed Using RECIST v. 1.1. Best Overall Confirmed Response.	Baseline (within 28 days prior to Day 1), then every 8 weeks until progressive disease (PD), start of other anticancer therapy, withdrawal of consent, or death (up to approximately 29 months)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically or cytologically confirmed mCRC not amenable to potentially curative resection with at least one measurable metastatic lesion, as defined by RECIST v1.1
Eastern Cooperative Oncology Group (World Health Organization) performance status of 0 or 1
Adequate hematologic, liver, coagulation, renal, and cardiovascular function
Recovery from all reversible AEs of previous medical therapies to baseline or National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 1, except for alopecia (any grade)
Negative serum pregnancy test within 7 days prior to starting study treatment in premenopausal women and women less than (< 2) years after the onset of menopause

Exclusion Criteria:

Any prior systemic therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors, immunotherapy, hormonal therapy) before Day 1 of Cycle 1 for treatment of mCRC
Malignancies other than CRC within 5 years prior to randomization, except for those with a minimal risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ treated surgically with curative intent
Radiotherapy within 28 days and abdominal/ pelvic radiotherapy within 60 days prior to Day 1 of Cycle 1, except palliative radiotherapy to bone lesions within 7 days prior to Day 1 of Cycle 1
Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to Day 1 of Cycle
Pregnant or lactating women
Symptomatic central nervous system (CNS) metastases or carcinomatous meningitis. Asymptomatic patients must be clinically stable with regard to their CNS/ meningeal metastatic involvement, have completed previous therapy (including radiation and/ or surgery) at least 4 weeks prior to study drug administration, are not receiving steroid therapy or taper, and are not receiving anti-convulsive medication for any CNS involvement
Active infection requiring IV antibiotics
Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids, or the equivalent of less than or equal to (</=) 10 mg/day prednisone
Sensory peripheral neuropathy greater than or equal to (>/=) Grade 2
Significant cardiovascular or cerebrovascular disease within 6 months prior to Day 1 of Cycle 1
Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation
Current use of anticoagulants at therapeutic doses within 7 days prior to study drug administration. Prophylactic use of unfractioned heparin or low molecular weight heparin is permitted
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to Day 1 of Cycle 1
History of intra-abdominal inflammatory process within 6 months prior to Day 1 of Cycle 1 including but not limited to peptic ulcer disease, diverticulitis, or colitis
Colonic prosthesis (stent) implant in place
History of abdominal or tracheo-oesophageal fistula or gastrointestinal (GI) perforation or intra abdominal abscess within 6 months prior to Day 1 of Cycle 1
History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or a requirement for routine parenteral hydration, parenteral nutrition, or tube feeding within 6 months prior to Day 1 of Cycle 1
Chronic daily treatment with NSAID (occasional use for the symptomatic relief of medical conditions, for example headache or fever is allowed)
Chronic daily treatment with corticosteroids (dose > 10 mg/day methylprednisolone equivalent) excluding inhaled steroids
Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
Metastatic disease that involve major airways or blood vessels, or centrally located mediastinal tumor masses (< 30 millimeter from the carina) of large volume
History of bronchopulmonary hemorrhage NCI CTCAE >/= Grade 2 within 2 months prior to randomization
Severe, nonhealing or open wound, active ulcer, or untreated bone fracture
Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene polymorphism predisposing the patient for 5-FU toxicity
Any other condition, diseases, metabolic dysfunction, active or uncontrolled infections/inflammation, physical examination finding, mental status or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates participation in the clinical study due to safety concerns, compliance with clinical study procedures or that may affect the interpretation of the results

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Alabama Oncology		Birmingham	Alabama	35211	United States
Arizona Clinical Research Ctr

ID	Title	Description
FG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.
FG001	Vanucizumab + mFOLFOX-6

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 10, 2016	Jan 6, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression-free Survival (PFS), Time to Event

Efficacy of vanucizumab was evaluated in terms of PFS as Investigator-Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). PFS was defined as the time between randomization and the date of first documented disease progression or death from any cause on study, whichever occurred first. Death on study was defined as death from any cause within 30 days of the last study treatment.

This analysis was based on the ITT population, which consisted of all participants who were randomized (Part II only) and received any amount of the study treatment (5 FU/folinic acid, oxaliplatin, bevacizumab, or vanucizumab) in the bevacizumab + mFOLFOX-6 and vanucizumab + mFOLFOX-6 arms. Participants in the safety-run in were not included.

Posted

Median

95% Confidence Interval

days

Baseline, every 8 weeks, up to approximately 29 months

ID	Title	Description
OG000	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.
OG001	Bevacizumab + mFOLFOX-6	In the induction therapy participants received bevacizumab at a dose of 5 milligram per kilogram (mg/kg) as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received bevacizumab at a dose of 5 milligram per kilogram (mg/kg) as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Units	Counts
Participants	OG00094 OG00195

Title

Denominators

Categories

Title	Measurements
	OG000338.0(312.0 to 381.0) OG001309.0(284.0 to 352.0)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Kaplan-Meier methods were used to estimate median PFS for each treatment arm and the 95% CIs for median PFS were computed using the Brookmeyer and Crowley method. The stratified Cox proportional hazard was used to estimate the hazard ratio (i.e., the magnitude of the treatment effect) and the corresponding 95% confidence interval. The stratification factors are number of metastatic sites (1 vs. >1) and country/region (USA vs rest of the world).	Regression, Cox		= 0.6753	log-rank	Hazard Ratio (HR)	0.91			2-Sided	95	0.60	1.39					Other

Secondary

Percentage of Participants With Objective Response (ORR) as Assessed Using RECIST v. 1.1

Efficacy of vanucizumab was evaluated in terms of Percentage of Participants With ORR as Investigator-Assessed Using RECIST v. 1.1. Best Overall Confirmed Response.

Posted

Number

95% Confidence Interval

Percentage of Participants

Baseline (within 28 days prior to Day 1), then every 8 weeks until progressive disease (PD), start of other anticancer therapy, withdrawal of consent, or death (up to approximately 29 months)

ID	Title	Description
OG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.
OG001	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Secondary

Duration of Objective Response, as Assessed Using RECIST v. 1.1

Efficacy of vanucizumab was evaluated in terms of duration of objective response as assessed using RECIST v. 1.1. This was computed using the PFS definition with death on study (deaths that occurred outside the 30 days window from the last study treatment are excluded).

This analysis was based on the ITT population, which consisted of all participants in the bevacizumab + mFOLFOX-6 and vanucizumab + mFOLFOX-6 arms. Participants in the safety-run in were not included.

Posted

Median

95% Confidence Interval

days

Baseline (within 28 days prior to Day 1), then every 8 weeks until PD, start of other anticancer therapy, withdrawal of consent, or death (up to approximately 29 months)

ID	Title	Description
OG000	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.
OG001

Secondary

Overall Survival (OS)

Efficacy of vanucizumab was evaluated in terms of OS as the time from randomization until death from any cause. 99999 = data not estimable due to the low number of deaths.

Posted

Median

95% Confidence Interval

days

Baseline until death from any cause (maximum up to approximately 3.5 years)

ID	Title	Description
OG000	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.
OG001	Bevacizumab + mFOLFOX-6	In the induction therapy participants received bevacizumab at a dose of 5 milligram per kilogram (mg/kg) as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received bevacizumab at a dose of 5 milligram per kilogram (mg/kg) as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Secondary

Percentage of Participants With Adverse Events (AEs)

Safety is evaluated in terms of percentage of participants with at least one serious adverse event and percentage of participants with at least one adverse event.

n for the vanucizumab + mFOLFOX-6 arm changed from 94 to 93 due to the withdrawal of a participant that was randomized to this arm, but received only chemotherapy before leaving the study. This participant is included in the ITT population but not in the safety population.

Posted

Number

Percentage of Participants

Up to approximately 29 months

ID	Title	Description
OG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.
OG001	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Secondary

Number of Participants With Human Anti-human Antibodies (HAHAs) Against Vanucizumab

Safety is evaluated in terms of number of participants with Human Anti-human Antibodies (HAHAs) Against Vanucizumab.

Endpoint includes only arms in which the participants received vanucizumab. n for the vanucizumab + mFOLFOX-6 arm changed from 94 to 93 due to the withdrawal of a participant that was randomized to this arm, but received only chemotherapy before leaving the study. This participant is included in the ITT population but not in the safety population.

Posted

Count of Participants

Participants

End of study (EoS, within 28 to 42 days after last dose, latest at 29 months)

ID	Title	Description
OG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.
OG001	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Secondary

Area Under the Plasma Concentration-Time Curve (AUC) of Vanucizumab

PK profile of vanucizumab was evaluated in terms of AUC

This endpoint was only reported for arms in which the participants received vanucizumab.

Posted

Geometric Mean

Geometric Coefficient of Variation

hr*ug/ml

Cycles 1 and 8 of parts 1 and 2

ID	Title	Description
OG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.
OG001	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Secondary

Maximum Observed Plasma Concentration (Cmax) of Vanucizumab

PK profile of vanucizumab was evaluated in terms of Cmax

This endpoint was only reported for arms in which the participants received vanucizumab.

Posted

Geometric Mean

Geometric Coefficient of Variation

ug/ml

Cycles 1 and 8 of parts 1 and 2

ID	Title	Description
OG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.
OG001	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Secondary

Minimum Observed Plasma Concentration (Clast) of Vanucizumab

PK profile of vanucizumab was evaluated in terms of Clast

Data were collected and analyzed for the reported arms only.

Posted

Geometric Mean

Geometric Coefficient of Variation

ug/ml

Cycles 1 and 8 of parts 1 and 2

ID	Title	Description
OG000	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Units	Counts
Participants	OG000

Secondary

Time to Reach Cmax (Tmax) of Vanucizumab

PK profile of vanucizumab was evaluated in terms of Tmax

This endpoint was only reported for arms in which the participants received vanucizumab.

Posted

Median

Full Range

Cycles 1 and 8 of parts 1 and 2

ID	Title	Description
OG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.
OG001	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Secondary

Plasma Terminal Half-Life (t1/2) of Vanucizumab

PK profile of vanucizumab was evaluated in terms of t1/2, values are reported for cycle 8 of both part 1 (safety run-in) and part 2 of the study.

This endpoint was only reported for arms in which the participants received vanucizumab.

Posted

Geometric Mean

Geometric Coefficient of Variation

Cycle 8

ID	Title	Description
OG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.
OG001	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Secondary

Plasma Clearance at Steady State (CLss) of Vanucizumab

PK profile of vanucizumab was evaluated in terms of CLss, values are reported for cycle 8 of both part 1 (safety run-in) and part 2 of the study.

This endpoint was only reported for arms in which the participants received vanucizumab.

Posted

Geometric Mean

Geometric Coefficient of Variation

ml/hr

Cycle 8

ID	Title	Description
OG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.
OG001	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Secondary

Volume of Distribution at Steady State (Vss) of Vanucizumab

PK profile of vanucizumab was evaluated in terms of Vss, values are reported for cycle 8 of both part 1 (safety run-in) and part 2 of the study.

This endpoint was only reported for arms in which the participants received vanucizumab.

Posted

Geometric Mean

Geometric Coefficient of Variation

Cycle 8

ID	Title	Description
OG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.
OG001	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Secondary

Cmax Accumulation Ratio (AR) of Vanucizumab

PK profile of vanucizumab was evaluated in terms of Cmax Ratio, values are reported for cycle 8 of both part 1 (safety run-in) and part 2 of the study.

This endpoint was only reported for arms in which the participants received vanucizumab.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio

Cycle 8

ID	Title	Description
OG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.
OG001	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0025 events5 affected95 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0011 events1 affected93 at risk EG0022 events2 affected95 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Angina unstable	Cardiac disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Cardiac arrest	Cardiac disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Cardiac disorder	Cardiac disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Cardiac failure	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Coronary artery disease	Cardiac disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Myocardial Ischaemia	Cardiac disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0023 events3 affected95 at risk
Anal ulcer	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Colitis	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Constipation	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0012 events1 affected93 at risk EG0021 events1 affected95 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected93 at risk EG0023 events3 affected95 at risk
Diverticular perforation	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Enterovesical fistula	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Gastrointestinal perforation	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0022 events2 affected95 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0013 events3 affected93 at risk EG0023 events3 affected95 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0013 events3 affected93 at risk EG0022 events2 affected95 at risk
Large intestinal obstruction	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0021 events1 affected95 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0013 events3 affected93 at risk EG0021 events1 affected95 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0012 events1 affected93 at risk EG0020 events0 affected95 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0012 events1 affected93 at risk EG0020 events0 affected95 at risk
Subileus	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0013 events3 affected93 at risk EG0021 events1 affected95 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0011 events1 affected93 at risk EG0021 events1 affected95 at risk
Asthenia	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Complication associated with device	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
General physical health deterioration	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Non-cardiac chest pain	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Oedema peripheral	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Pyrexia	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0014 events4 affected93 at risk EG0028 events4 affected95 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Hypersensitivity	Immune system disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Bacteraemia	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Diarrhoea infectious	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Endocarditis	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Enterococcal bacteraemia	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Pneumonia	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0023 events3 affected95 at risk
Pneumonia pneumococcal	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Sepsis	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0021 events1 affected95 at risk
Septic shock	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0022 events2 affected95 at risk
Splenic abscess	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Urinary tract infection	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected93 at risk EG0024 events4 affected95 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Gastrointestinal anastomotic leak	Injury, poisoning and procedural complications	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0012 events1 affected93 at risk EG0021 events1 affected95 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Infected neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Tumor obstruction	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Guillain-Barre syndrome	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Seizure	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Spinal cord compression	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0022 events2 affected95 at risk
Device dislocation	Product Issues	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Device occlusion	Product Issues	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Mental status changes	Psychiatric disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Renal colic	Renal and urinary disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Renal failure	Renal and urinary disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0012 events1 affected93 at risk EG0020 events0 affected95 at risk
Renal impairment	Renal and urinary disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Female genital tract fistula	Reproductive system and breast disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected93 at risk EG0020 events0 affected95 at risk
Aortic thrombosis	Vascular disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Hypertension	Vascular disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected93 at risk EG0021 events1 affected95 at risk
Vasospasm	Vascular disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Myocardial infarction	Cardiac disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Oesophageal ulcer	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Pyelonephritis	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0022 events1 affected95 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG0020 events0 affected95 at risk
Obstructive nephropathy	Renal and urinary disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected93 at risk EG0021 events1 affected95 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.0	Non-systematic Assessment	EG0003 events3 affected8 at risk EG0017 events6 affected93 at risk EG00219 events12 affected95 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 19.0	Non-systematic Assessment	EG0006 events4 affected8 at risk EG00152 events40 affected93 at risk EG00263 events43 affected95 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 19.0	Non-systematic Assessment	EG0004 events3 affected8 at risk EG0016 events4 affected93 at risk EG0029 events8 affected95 at risk
Cataract	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Eyelid oedema	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Lacrimation increased	Eye disorders	MedDRA 19.0	Non-systematic Assessment	EG0002 events2 affected8 at risk EG0015 events4 affected93 at risk EG0027 events6 affected95 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0003 events2 affected8 at risk EG00133 events27 affected93 at risk EG00222 events22 affected95 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0018 events7 affected93 at risk EG0023 events3 affected95 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0019 events6 affected93 at risk EG00215 events14 affected95 at risk
Constipation	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0005 events3 affected8 at risk EG00136 events26 affected93 at risk EG00252 events31 affected95 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0008 events6 affected8 at risk EG001107 events56 affected93 at risk EG002133 events57 affected95 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0014 events4 affected93 at risk EG0026 events5 affected95 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG00115 events11 affected93 at risk EG00212 events8 affected95 at risk
Flatulence	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0016 events5 affected93 at risk EG0023 events3 affected95 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Hypoaesthesia oral	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0006 events6 affected8 at risk EG00193 events52 affected93 at risk EG00298 events55 affected95 at risk
Odynophagia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Oral pain	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0016 events6 affected93 at risk EG0021 events1 affected95 at risk
Proctalgia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG00125 events15 affected93 at risk EG00215 events11 affected95 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG00140 events31 affected93 at risk EG00246 events29 affected95 at risk
Asthenia	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0006 events3 affected8 at risk EG00189 events41 affected93 at risk EG002129 events42 affected95 at risk
Chest discomfort	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Chest pain	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0015 events5 affected93 at risk EG0023 events3 affected95 at risk
Fatigue	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG00133 events26 affected93 at risk EG00228 events23 affected95 at risk
Mass	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Mucosal inflammation	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0006 events4 affected8 at risk EG00142 events23 affected93 at risk EG00268 events31 affected95 at risk
Oedema peripheral	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0005 events3 affected8 at risk EG00115 events11 affected93 at risk EG0023 events3 affected95 at risk
Pyrexia	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG00124 events17 affected93 at risk EG00222 events18 affected95 at risk
Temperature intolerance	General disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG00115 events11 affected93 at risk EG00216 events10 affected95 at risk
Ear infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Furuncle	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Gingivitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Nasopharyngitis	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0002 events2 affected8 at risk EG0019 events8 affected93 at risk EG00212 events9 affected95 at risk
Oral candidiasis	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0015 events5 affected93 at risk EG0022 events1 affected95 at risk
Periodontitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Rhinitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0002 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Sinusitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0012 events2 affected93 at risk EG00215 events14 affected95 at risk
Urinary tract infection	Infections and infestations	MedDRA 19.0	Non-systematic Assessment	EG0003 events2 affected8 at risk EG00112 events11 affected93 at risk EG00214 events10 affected95 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0002 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG00126 events19 affected93 at risk EG00218 events13 affected95 at risk
Alanine aminotransferase increased	Investigations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0014 events3 affected93 at risk EG0025 events5 affected95 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0017 events3 affected93 at risk EG0027 events7 affected95 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Lipase increased	Investigations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected93 at risk EG0029 events9 affected95 at risk
Platelet count decreased	Investigations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG00125 events10 affected93 at risk EG0026 events4 affected95 at risk
Weight decreased	Investigations	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG00113 events12 affected93 at risk EG00213 events13 affected95 at risk
Weight increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.0	Non-systematic Assessment	EG0003 events1 affected8 at risk EG00145 events29 affected93 at risk EG00267 events33 affected95 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG00113 events9 affected93 at risk EG0027 events7 affected95 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected93 at risk EG00210 events6 affected95 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG00110 events9 affected93 at risk EG00211 events10 affected95 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0004 events2 affected8 at risk EG0014 events4 affected93 at risk EG00210 events8 affected95 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0019 events8 affected93 at risk EG00220 events16 affected95 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0002 events1 affected8 at risk EG0011 events1 affected93 at risk EG0026 events5 affected95 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG00112 events9 affected93 at risk EG0029 events7 affected95 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG00111 events8 affected93 at risk EG00212 events8 affected95 at risk
Pain in extremitiy	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0002 events2 affected8 at risk EG0013 events3 affected93 at risk EG0028 events6 affected95 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0016 events6 affected93 at risk EG0024 events2 affected95 at risk
Aphonia	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0015 events5 affected93 at risk EG0022 events2 affected95 at risk
Dizziness	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG00116 events11 affected93 at risk EG00217 events12 affected95 at risk
Dysaesthesia	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0003 events1 affected8 at risk EG00132 events15 affected93 at risk EG00279 events22 affected95 at risk
Dysgeusia	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0006 events5 affected8 at risk EG00116 events16 affected93 at risk EG00226 events22 affected95 at risk
Headache	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0002 events2 affected8 at risk EG00116 events15 affected93 at risk EG00230 events19 affected95 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0008 events3 affected8 at risk EG00131 events18 affected93 at risk EG00266 events28 affected95 at risk
Neurotoxicity	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG00114 events8 affected93 at risk EG0022 events2 affected95 at risk
Paraesthesia	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG00117 events15 affected93 at risk EG00224 events17 affected95 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 19.0	Non-systematic Assessment	EG0004 events2 affected8 at risk EG00183 events33 affected93 at risk EG00272 events28 affected95 at risk
Anxiety	Psychiatric disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0019 events9 affected93 at risk EG0028 events8 affected95 at risk
Depression	Psychiatric disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0016 events6 affected93 at risk EG0021 events1 affected95 at risk
Insomnia	Psychiatric disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG00111 events11 affected93 at risk EG00213 events12 affected95 at risk
Dysuria	Renal and urinary disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0015 events5 affected93 at risk EG0028 events6 affected95 at risk
Proteinuria	Renal and urinary disorders	MedDRA 19.0	Non-systematic Assessment	EG0005 events1 affected8 at risk EG00115 events12 affected93 at risk EG00217 events10 affected95 at risk
Urinary tract pain	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG00112 events10 affected93 at risk EG00213 events10 affected95 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0002 events1 affected8 at risk EG00113 events13 affected93 at risk EG00212 events9 affected95 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG00112 events10 affected93 at risk EG00212 events10 affected95 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0002 events2 affected8 at risk EG00127 events20 affected93 at risk EG00236 events28 affected95 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0014 events4 affected93 at risk EG0027 events7 affected95 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0015 events4 affected93 at risk EG0025 events5 affected95 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0015 events5 affected93 at risk EG00214 events14 affected95 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0002 events2 affected8 at risk EG00114 events9 affected93 at risk EG00223 events16 affected95 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0018 events5 affected93 at risk EG00210 events8 affected95 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0002 events2 affected8 at risk EG0017 events5 affected93 at risk EG0025 events4 affected95 at risk
Embolism venous	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0020 events0 affected95 at risk
Hypertension	Vascular disorders	MedDRA 19.0	Non-systematic Assessment	EG0009 events5 affected8 at risk EG00175 events42 affected93 at risk EG00250 events27 affected95 at risk
Hypotension	Vascular disorders	MedDRA 19.0	Non-systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected93 at risk EG0026 events6 affected95 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 19.0	Non-systematic Assessment	EG0000 events0 affected8 at risk EG0016 events5 affected93 at risk EG0025 events4 affected95 at risk

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases

ID	Term
D005472	Fluorouracil
D000068258	Bevacizumab
D002955	Leucovorin
D000077150	Oxaliplatin
C000619444	vanucizumab

ID	Term
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D005575	Formyltetrahydrofolates
D013763	Tetrahydrofolates
D005492	Folic Acid
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D003067	Coenzymes
D045762	Enzymes and Coenzymes
D056831	Coordination Complexes
D009930	Organic Chemicals

ID	Title	Description
BG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.
BG001	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.
BG002	Bevacizumab + mFOLFOX-6	In the induction therapy participants received bevacizumab at a dose of 5 milligram per kilogram (mg/kg) as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received bevacizumab at a dose of 5 milligram per kilogram (mg/kg) as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Safety Run-In	8 eligible participants received 2000 milligrams (mg) vanucizumab + mFOLFOX-6 every two weeks for up to 8 cycles in order to confirm the dose and schedule for the randomized part.	3	8	3	8	8	8
EG001	Vanucizumab + mFOLFOX-6	In the induction therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received vanucizumab at a dose of 2000 mg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.	24	93	46	93	91	93
EG002	Bevacizumab + mFOLFOX-6	In the induction therapy participants received bevacizumab at a dose of 5 milligram per kilogram (mg/kg) as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months). Subsequently, in the maintenance therapy participants received bevacizumab at a dose of 5 milligram per kilogram (mg/kg) as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.	27	95	41	95	94	95