A Study of Bevacizumab (Avastin) in Participants With New... | NCT00865189

ID	Type	Description	Link
2006-003472-35	EudraCT Number

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	Experimental	In this arm, participants will undergo 3 phases of treatment. During the Phase 1, participants will receive induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 will include 7 weeks of bevacizumab + chemoradiotherapy (intravenous [IV] infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 will be surgery involving a radical rectal excision using the total mesorectal excision (TME) technique.	Drug: Bevacizumab Drug: Oxaliplatin Drug: Folinic Acid Drug: 5-fluorouracil Radiation: Preoperative Radiotherapy Procedure: Surgery
Arm B (Bevacizumab, Chemoradiotherapy)	Experimental	In this arm, participants will receive the Phase 2 and Phase 3 treatments only. The phase 2 will include 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 will be surgery involving a radical rectal excision using the TME technique.	Drug: Bevacizumab Drug: 5-fluorouracil Radiation: Preoperative Radiotherapy Procedure: Surgery

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Bevacizumab	Drug	Bevacizumab will be administered at the fixed dose of 5 milligrams per kilogram (mg/kg) as an IV infusion over 30 to 90 minutes.	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Tumor Sterilization Defined by ypT0-N0	Tumor sterilization was defined as the absence of residual tumor cells in the resected specimen including lymph nodes (ypT0-N0). The rate of sterilization of the tumoral specimen was assessed after surgery on the surgical specimen by local review. Analyses were performed for participants who have been operated as defined by the protocol (within the study and TME technique) and for all participants who have been operated. Reported is the percentage of participants with tumor sterilization.	After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Tumor Down-Staging (ypT0-pT2)	A participant with a downstaging was defined as a participant with T3 (T describes the size of the original [primary] tumor) at inclusion and T2 or T1 or T0 after surgery, or with N+ (N describes lymph nodes involvement) at inclusion and N- after surgery and if T is equal at inclusion and after surgery. The clinical tumor-node-metastasis (cTNM) classification was used at inclusion and the pathological staging tumor and nodes (ypTN) classification after surgery. Reported is the percentage of participants with tumor downstaging of the surgical specimen according to the local review and centralized review.

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
ICO Paul Papin; Oncologie Medicale.		Angers		49055	France

PubMed Identifier	Type	Citation	Retractions
25122693	Derived	Borg C, Andre T, Mantion G, Boudghene F, Mornex F, Maingon P, Adenis A, Azria D, Piutti M, Morsli O, Bosset JF. Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study. Ann Oncol. 2014 Nov;25(11):2205-2210. doi: 10.1093/annonc/mdu377. Epub 2014 Aug 13.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (intravenous [IV] infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the total mesorectal excision (TME) technique.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.
BG001	Arm B (Bevacizumab, Chemoradiotherapy)	In this arm, participants received the Phase 2 and Phase 3 treatments only. The phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 was surgery involving a radical rectal excision using the TME technique.
BG002	Total	Total of all reporting groups

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

Percentage of Participants With Tumor Sterilization Defined by ypT0-N0

Tumor sterilization was defined as the absence of residual tumor cells in the resected specimen including lymph nodes (ypT0-N0). The rate of sterilization of the tumoral specimen was assessed after surgery on the surgical specimen by local review. Analyses were performed for participants who have been operated as defined by the protocol (within the study and TME technique) and for all participants who have been operated. Reported is the percentage of participants with tumor sterilization.

ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Posted

Number

95% Confidence Interval

percentage of participants

After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)

ID	Title	Description
OG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.
OG001	Arm B (Bevacizumab, Chemoradiotherapy)	In this arm, participants received the Phase 2 and Phase 3 treatments only. The phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 was surgery involving a radical rectal excision using the TME technique.

Units	Counts
Participants	OG00042 OG00144

Title

Denominators

Categories

Title	Measurements
	OG00023.8(12.1 to 39.5) OG00111.4(3.8 to 24.6)

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	This proportion was described for each treatment arm with a 95% confidence interval (CI) and compared with the standard proportion of 10% (CI) for each treatment arm.	Binomial test		0.015														Superiority or Other
OG001	This proportion was described for each treatment arm with a 95% CI and compared with the standard proportion of 10% (CI) using for each treatment arm.

Secondary

Percentage of Participants With Tumor Down-Staging (ypT0-pT2)

A participant with a downstaging was defined as a participant with T3 (T describes the size of the original [primary] tumor) at inclusion and T2 or T1 or T0 after surgery, or with N+ (N describes lymph nodes involvement) at inclusion and N- after surgery and if T is equal at inclusion and after surgery. The clinical tumor-node-metastasis (cTNM) classification was used at inclusion and the pathological staging tumor and nodes (ypTN) classification after surgery. Reported is the percentage of participants with tumor downstaging of the surgical specimen according to the local review and centralized review.

ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome. "n" = participants who were evaluable for specified category.

Posted

Number

95% Confidence Interval

percentage of participants

After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)

ID	Title	Description
OG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.

Secondary

Percentage of Participants With Local and Distant Recurrences

The percentage of participants with a recurrence was described by type of recurrence (local and distant recurrence).

ITT population

Posted

Number

95% Confidence Interval

percentage of participants

After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)

ID	Title	Description
OG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.
OG001	Arm B (Bevacizumab, Chemoradiotherapy)	In this arm, participants received the Phase 2 and Phase 3 treatments only. The phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 was surgery involving a radical rectal excision using the TME technique.

Secondary

Percentage of Participants With Second Cancer, Local or Regional Recurrence, Distant Metastasis, or Death

ITT population

Posted

Number

percentage of participants

Baseline up to approximately 6 years

ID	Title	Description
OG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.
OG001	Arm B (Bevacizumab, Chemoradiotherapy)	In this arm, participants received the Phase 2 and Phase 3 treatments only. The phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 was surgery involving a radical rectal excision using the TME technique.

Secondary

Disease-Free Survival (DFS)

The DFS was defined as the time from the first treatment intake to disease recurrence assessed (second primary cancer, local or distant recurrence, distant metastases) or death from any cause. The DFS was analyzed using Kaplan-Meier method.

ITT population

Posted

Median

95% Confidence Interval

months

From first time of the treatment administration to the date of second cancer, local or regional recurrence, distant metastasis or death from any cause (up to approximately 6 years)

ID	Title	Description
OG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.
OG001	Arm B (Bevacizumab, Chemoradiotherapy)	In this arm, participants received the Phase 2 and Phase 3 treatments only. The phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 was surgery involving a radical rectal excision using the TME technique.

Secondary

Percentage of Participants Who Died

ITT population

Posted

Number

percentage of participants

Baseline up to approximately 6 years

ID	Title	Description
OG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.
OG001	Arm B (Bevacizumab, Chemoradiotherapy)	In this arm, participants received the Phase 2 and Phase 3 treatments only. The phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 was surgery involving a radical rectal excision using the TME technique.

Secondary

Overall Survival

The overall survival was defined as the time from the first treatment intake to death from any cause.

ITT population

Posted

Median

95% Confidence Interval

months

From the first treatment administration to the date of death (up to approximately 6 years)

ID	Title	Description
OG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.
OG001	Arm B (Bevacizumab, Chemoradiotherapy)	In this arm, participants received the Phase 2 and Phase 3 treatments only. The phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 was surgery involving a radical rectal excision using the TME technique.

Secondary

Number of Cycles of Induction Chemotherapy

ITT population. Only Arm A participants received induction treatment.

Posted

Mean

Standard Deviation

cycles

6 cycles (12 weeks; cycle length = 14 days)

ID	Title	Description
OG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.

Units	Counts
Participants	OG000

Secondary

Number of Cycles of Chemotherapy

ITT population

Posted

Mean

Standard Deviation

cycles

Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7

ID	Title	Description
OG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.
OG001	Arm B (Bevacizumab, Chemoradiotherapy)	In this arm, participants received the Phase 2 and Phase 3 treatments only. The phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 was surgery involving a radical rectal excision using the TME technique.

Secondary

Number of Cycles of Radiotherapy

ITT population

Posted

Mean

Standard Deviation

cycles

Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7

ID	Title	Description
OG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.
OG001	Arm B (Bevacizumab, Chemoradiotherapy)	In this arm, participants received the Phase 2 and Phase 3 treatments only. The phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 was surgery involving a radical rectal excision using the TME technique.

Secondary

Percentage of Participants With Surgery

The surgery involving a radical rectal excision using the TME technique.

ITT population

Posted

Number

percentage of participants

Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment

ID	Title	Description
OG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.
OG001	Arm B (Bevacizumab, Chemoradiotherapy)	In this arm, participants received the Phase 2 and Phase 3 treatments only. The phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 was surgery involving a radical rectal excision using the TME technique.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)	In this arm, participants underwent 3 phases of treatment. During the Phase 1, participants received induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 was surgery involving a radical rectal excision using the TME technique.			21	46	46	46
EG001	Arm B (Bevacizumab, Chemoradiotherapy)	In this arm, participants received the Phase 2 and Phase 3 treatments only. The phase 2 consisted of 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 was surgery involving a radical rectal excision using the TME technique.			18	45	44	45

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anastomotic fistula	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0004 affected46 at risk EG0014 affected45 at risk
Incisional hernia	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0003 affected46 at risk EG0012 affected45 at risk
Intestinal anastomosis complication	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0002 affected46 at risk EG0010 affected45 at risk
Wound complication	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0012 affected45 at risk
Catheter site infection	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Gastrointestinal anastomotic complication	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Gastrointestinal stoma complication	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Post procedural infection	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0012 affected45 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0011 affected45 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0011 affected45 at risk
Colitis ischaemic	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Diverticulitis	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Enteritis	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Gastrointestinal perforation	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Intra-abdominal haematoma	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Intussusception	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Subileus	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Postoperative abscess	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0012 affected45 at risk
Abdominal wall abscess	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Gastroenteritis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Intervertebral discitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Pelvic abscess	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Perineal abscess	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Pilonidal cyst	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Sepsis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Septic shock	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Female genital tract fistula	Reproductive system and breast disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0011 affected45 at risk
Perineal pain	Reproductive system and breast disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Rectoprostatic fistula	Reproductive system and breast disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Vaginal fistula	Reproductive system and breast disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Phlebitis	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0011 affected45 at risk
Embolism venous	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Shock haemorrhagic	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Thrombophlebitis	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Catheter site pain	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Complication associated with device	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Localised oedema	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0012 affected45 at risk
Urinary retention	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0012 affected45 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected46 at risk EG0010 affected45 at risk
Sinus arrhythmia	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Tachycardia	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Ruptured cerebral aneurysm	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Wernicke's encephalopathy	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0011 affected45 at risk
Neutrophil count decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0010 affected45 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00025 affected46 at risk EG00124 affected45 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00024 affected46 at risk EG0017 affected45 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00015 affected46 at risk EG0013 affected45 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0007 affected46 at risk EG0015 affected45 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0009 affected46 at risk EG0012 affected45 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0005 affected46 at risk EG0014 affected45 at risk
Anorectal discomfort	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0017 affected45 at risk
Proctalgia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 affected46 at risk EG0013 affected45 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 affected46 at risk EG0012 affected45 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0006 affected46 at risk EG0010 affected45 at risk
Rectal tenesmus	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected46 at risk EG0013 affected45 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected46 at risk EG0011 affected45 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected46 at risk EG0013 affected45 at risk
Gingivitis	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected46 at risk EG0010 affected45 at risk
Proteinuria	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG00020 affected46 at risk EG00113 affected45 at risk
Dysuria	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG00012 affected46 at risk EG00110 affected45 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected46 at risk EG0013 affected45 at risk
Asthenia	General disorders	MedDRA 18.1	Non-systematic Assessment	EG00017 affected46 at risk EG0016 affected45 at risk
Mucosal inflammation	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0007 affected46 at risk EG0014 affected45 at risk
Fatigue	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 affected46 at risk EG0012 affected45 at risk
Pyrexia	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected46 at risk EG0010 affected45 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG00022 affected46 at risk EG0010 affected45 at risk
Paraesthesia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG00011 affected46 at risk EG0012 affected45 at risk
Headache	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0007 affected46 at risk EG0012 affected45 at risk
Dysaesthesia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 affected46 at risk EG0010 affected45 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0002 affected46 at risk EG0014 affected45 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0002 affected46 at risk EG0015 affected45 at risk
Anastomotic fistula	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0003 affected46 at risk EG0012 affected45 at risk
Wound complication	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0004 affected46 at risk EG0011 affected45 at risk
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0003 affected46 at risk EG0011 affected45 at risk
Neutrophil count decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG00012 affected46 at risk EG0011 affected45 at risk
Blood potassium decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0005 affected46 at risk EG0011 affected45 at risk
Weight decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0003 affected46 at risk EG0012 affected45 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00015 affected46 at risk EG0012 affected45 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 affected46 at risk EG0010 affected45 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected46 at risk EG0010 affected45 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected46 at risk EG0010 affected45 at risk
Hypertension	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG00011 affected46 at risk EG0017 affected45 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected46 at risk EG0010 affected45 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected46 at risk EG0011 affected45 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0006 affected46 at risk EG0013 affected45 at risk
Proctitis	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00021 affected46 at risk EG00118 affected45 at risk

ID	Term
D015179	Colorectal Neoplasms
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases

ID	Term
D000068258	Bevacizumab
D000077150	Oxaliplatin
D002955	Leucovorin
D005472	Fluorouracil
D013514	Surgical Procedures, Operative

ID	Term
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
D056831	Coordination Complexes
D009930	Organic Chemicals
D005575	Formyltetrahydrofolates
D013763	Tetrahydrofolates
D005492	Folic Acid
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D003067	Coenzymes
D045762	Enzymes and Coenzymes
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring