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A Study of Bevacizumab (Avastin) in Participants With Newly Diagnosed Locally Advanced Rectal Cancer (INOVA)

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ClinicalTrials.gov Identifier: NCT00865189
Recruitment Status : Completed
First Posted : March 19, 2009
Results First Posted : August 4, 2017
Last Update Posted : August 4, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rectal Cancer
Interventions Drug: Bevacizumab
Drug: Oxaliplatin
Drug: Folinic Acid
Drug: 5-fluorouracil
Radiation: Preoperative Radiotherapy
Procedure: Surgery
Enrollment 91
Recruitment Details  
Pre-assignment Details A total of 92 participants with resectable rectal cancer were selected and 91 participants were randomized into the study. One participant was not randomized due to non-compliance with the inclusion/exclusion criteria.
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 46 45
Completed 34 26
Not Completed 12 19
Reason Not Completed
Other             1             2
Death             4             11
Lost to Follow-up             6             6
Withdrawal by Subject             1             0
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy) Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 46 45 91
Hide Baseline Analysis Population Description
Intent to treat (ITT) population included all the randomized participants who received at least one dose of treatment.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 46 participants 45 participants 91 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
33
  71.7%
29
  64.4%
62
  68.1%
>=65 years
13
  28.3%
16
  35.6%
29
  31.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 46 participants 45 participants 91 participants
Female
15
  32.6%
15
  33.3%
30
  33.0%
Male
31
  67.4%
30
  66.7%
61
  67.0%
1.Primary Outcome
Title Percentage of Participants With Tumor Sterilization Defined by ypT0-N0
Hide Description 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.
Time Frame After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome.
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 42 44
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
23.8
(12.1 to 39.5)
11.4
(3.8 to 24.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method Binomial test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm B (Bevacizumab, Chemoradiotherapy)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.906
Comments [Not Specified]
Method Binomial test
Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Tumor Down-Staging (ypT0-pT2)
Hide Description 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.
Time Frame After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome. “n” = participants who were evaluable for specified category.
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 41 44
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Downstaging, local review (n=41, 44)
65.9
(51.3 to 80.4)
54.5
(39.8 to 69.3)
Downstaging, centralized review (n=39, 43)
64.1
(49.0 to 79.2)
55.8
(41.0 to 70.7)
3.Secondary Outcome
Title Percentage of Participants With Local and Distant Recurrences
Hide Description The percentage of participants with a recurrence was described by type of recurrence (local and distant recurrence).
Time Frame After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 46 45
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Local recurrence
2.2
(0.1 to 11.5)
6.7
(1.4 to 18.3)
Distant recurrence
17.4
(7.8 to 31.4)
13.3
(5.1 to 26.8)
4.Secondary Outcome
Title Percentage of Participants With Second Cancer, Local or Regional Recurrence, Distant Metastasis, or Death
Hide Description [Not Specified]
Time Frame Baseline up to approximately 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 46 45
Measure Type: Number
Unit of Measure: percentage of participants
30.4 33.3
5.Secondary Outcome
Title Disease-Free Survival (DFS)
Hide Description 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.
Time Frame 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 46 45
Median (95% Confidence Interval)
Unit of Measure: months
68.3 [1] 
(68.3 to NA)
NA [2] 
(53.0 to NA)
[1]
Upper limit of 95% CI was not reached due to low number of DFS-events.
[2]
Median and upper limit of 95% CI were not reached due to low number of DFS-events.
6.Secondary Outcome
Title Percentage of Participants Who Died
Hide Description [Not Specified]
Time Frame Baseline up to approximately 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 46 45
Measure Type: Number
Unit of Measure: percentage of participants
8.7 24.4
7.Secondary Outcome
Title Overall Survival
Hide Description The overall survival was defined as the time from the first treatment intake to death from any cause.
Time Frame From the first treatment administration to the date of death (up to approximately 6 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 46 45
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median and 95% CI were not reached due to low number of deaths.
8.Secondary Outcome
Title Number of Cycles of Induction Chemotherapy
Hide Description [Not Specified]
Time Frame 6 cycles (12 weeks; cycle length = 14 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only Arm A participants received induction treatment.
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 46
Mean (Standard Deviation)
Unit of Measure: cycles
5.8  (0.7)
9.Secondary Outcome
Title Number of Cycles of Chemotherapy
Hide Description [Not Specified]
Time Frame Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 46 45
Mean (Standard Deviation)
Unit of Measure: cycles
4.4  (1.5) 4.8  (0.5)
10.Secondary Outcome
Title Number of Cycles of Radiotherapy
Hide Description [Not Specified]
Time Frame Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 46 45
Mean (Standard Deviation)
Unit of Measure: cycles
4.5  (1.5) 5.0  (0.0)
11.Secondary Outcome
Title Percentage of Participants With Surgery
Hide Description The surgery involving a radical rectal excision using the TME technique.
Time Frame Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 46 45
Measure Type: Number
Unit of Measure: percentage of participants
91.3 97.8
Time Frame Baseline up to approximately 6 years
Adverse Event Reporting Description The safety population included all selected participants who received at least one dose of treatment and corresponded to the ITT population.
 
Arm/Group Title Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Affected / at Risk (%) Affected / at Risk (%)
Total   21/46 (45.65%)   18/45 (40.00%) 
Blood and lymphatic system disorders     
Febrile neutropenia * 1  2/46 (4.35%)  0/45 (0.00%) 
Cardiac disorders     
Sinus arrhythmia * 1  0/46 (0.00%)  1/45 (2.22%) 
Tachycardia * 1  1/46 (2.17%)  0/45 (0.00%) 
Gastrointestinal disorders     
Rectal haemorrhage * 1  1/46 (2.17%)  2/45 (4.44%) 
Diarrhoea * 1  1/46 (2.17%)  1/45 (2.22%) 
Intestinal obstruction * 1  1/46 (2.17%)  1/45 (2.22%) 
Colitis ischaemic * 1  0/46 (0.00%)  1/45 (2.22%) 
Diverticulitis * 1  1/46 (2.17%)  0/45 (0.00%) 
Enteritis * 1  1/46 (2.17%)  0/45 (0.00%) 
Gastrointestinal perforation * 1  1/46 (2.17%)  0/45 (0.00%) 
Intra-abdominal haematoma * 1  1/46 (2.17%)  0/45 (0.00%) 
Intussusception * 1  0/46 (0.00%)  1/45 (2.22%) 
Subileus * 1  0/46 (0.00%)  1/45 (2.22%) 
General disorders     
Catheter site pain * 1  0/46 (0.00%)  1/45 (2.22%) 
Complication associated with device * 1  0/46 (0.00%)  1/45 (2.22%) 
Localised oedema * 1  1/46 (2.17%)  0/45 (0.00%) 
Hepatobiliary disorders     
Cholecystitis acute * 1  0/46 (0.00%)  1/45 (2.22%) 
Infections and infestations     
Postoperative abscess * 1  0/46 (0.00%)  2/45 (4.44%) 
Abdominal wall abscess * 1  0/46 (0.00%)  1/45 (2.22%) 
Gastroenteritis * 1  1/46 (2.17%)  0/45 (0.00%) 
Infection * 1  1/46 (2.17%)  0/45 (0.00%) 
Intervertebral discitis * 1  0/46 (0.00%)  1/45 (2.22%) 
Pelvic abscess * 1  1/46 (2.17%)  0/45 (0.00%) 
Perineal abscess * 1  0/46 (0.00%)  1/45 (2.22%) 
Pilonidal cyst * 1  0/46 (0.00%)  1/45 (2.22%) 
Sepsis * 1  1/46 (2.17%)  0/45 (0.00%) 
Septic shock * 1  1/46 (2.17%)  0/45 (0.00%) 
Injury, poisoning and procedural complications     
Anastomotic fistula * 1  4/46 (8.70%)  4/45 (8.89%) 
Incisional hernia * 1  3/46 (6.52%)  2/45 (4.44%) 
Intestinal anastomosis complication * 1  2/46 (4.35%)  0/45 (0.00%) 
Wound complication * 1  0/46 (0.00%)  2/45 (4.44%) 
Catheter site infection * 1  0/46 (0.00%)  1/45 (2.22%) 
Gastrointestinal anastomotic complication * 1  1/46 (2.17%)  0/45 (0.00%) 
Gastrointestinal stoma complication * 1  0/46 (0.00%)  1/45 (2.22%) 
Post procedural infection * 1  0/46 (0.00%)  1/45 (2.22%) 
Wound dehiscence * 1  0/46 (0.00%)  1/45 (2.22%) 
Investigations     
Neutrophil count decreased * 1  1/46 (2.17%)  0/45 (0.00%) 
Metabolism and nutrition disorders     
Dehydration * 1  1/46 (2.17%)  2/45 (4.44%) 
Musculoskeletal and connective tissue disorders     
Osteonecrosis * 1  1/46 (2.17%)  0/45 (0.00%) 
Nervous system disorders     
Ruptured cerebral aneurysm * 1  1/46 (2.17%)  0/45 (0.00%) 
Wernicke's encephalopathy * 1  0/46 (0.00%)  1/45 (2.22%) 
Renal and urinary disorders     
Urinary retention * 1  0/46 (0.00%)  2/45 (4.44%) 
Acute kidney injury * 1  1/46 (2.17%)  0/45 (0.00%) 
Reproductive system and breast disorders     
Female genital tract fistula * 1  1/46 (2.17%)  1/45 (2.22%) 
Perineal pain * 1  1/46 (2.17%)  0/45 (0.00%) 
Rectoprostatic fistula * 1  1/46 (2.17%)  0/45 (0.00%) 
Vaginal fistula * 1  1/46 (2.17%)  0/45 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism * 1  1/46 (2.17%)  0/45 (0.00%) 
Vascular disorders     
Phlebitis * 1  1/46 (2.17%)  1/45 (2.22%) 
Embolism venous * 1  0/46 (0.00%)  1/45 (2.22%) 
Shock haemorrhagic * 1  1/46 (2.17%)  0/45 (0.00%) 
Thrombophlebitis * 1  1/46 (2.17%)  0/45 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Arm B (Bevacizumab, Chemoradiotherapy)
Affected / at Risk (%) Affected / at Risk (%)
Total   46/46 (100.00%)   44/45 (97.78%) 
Gastrointestinal disorders     
Diarrhoea * 1  25/46 (54.35%)  24/45 (53.33%) 
Nausea * 1  24/46 (52.17%)  7/45 (15.56%) 
Constipation * 1  15/46 (32.61%)  3/45 (6.67%) 
Abdominal pain * 1  7/46 (15.22%)  5/45 (11.11%) 
Rectal haemorrhage * 1  9/46 (19.57%)  2/45 (4.44%) 
Abdominal pain upper * 1  5/46 (10.87%)  4/45 (8.89%) 
Anorectal discomfort * 1  1/46 (2.17%)  7/45 (15.56%) 
Proctalgia * 1  4/46 (8.70%)  3/45 (6.67%) 
Haemorrhoids * 1  4/46 (8.70%)  2/45 (4.44%) 
Vomiting * 1  6/46 (13.04%)  0/45 (0.00%) 
Rectal tenesmus * 1  1/46 (2.17%)  3/45 (6.67%) 
Stomatitis * 1  3/46 (6.52%)  1/45 (2.22%) 
Abdominal pain lower * 1  0/46 (0.00%)  3/45 (6.67%) 
Gingivitis * 1  3/46 (6.52%)  0/45 (0.00%) 
Proctitis * 1  21/46 (45.65%)  18/45 (40.00%) 
General disorders     
Asthenia * 1  17/46 (36.96%)  6/45 (13.33%) 
Mucosal inflammation * 1  7/46 (15.22%)  4/45 (8.89%) 
Fatigue * 1  4/46 (8.70%)  2/45 (4.44%) 
Pyrexia * 1  3/46 (6.52%)  0/45 (0.00%) 
Infections and infestations     
Urinary tract infection * 1  2/46 (4.35%)  4/45 (8.89%) 
Injury, poisoning and procedural complications     
Wound dehiscence * 1  2/46 (4.35%)  5/45 (11.11%) 
Anastomotic fistula * 1  3/46 (6.52%)  2/45 (4.44%) 
Wound complication * 1  4/46 (8.70%)  1/45 (2.22%) 
Radiation skin injury * 1  3/46 (6.52%)  1/45 (2.22%) 
Investigations     
Neutrophil count decreased * 1  12/46 (26.09%)  1/45 (2.22%) 
Blood potassium decreased * 1  5/46 (10.87%)  1/45 (2.22%) 
Weight decreased * 1  3/46 (6.52%)  2/45 (4.44%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  6/46 (13.04%)  3/45 (6.67%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms * 1  3/46 (6.52%)  0/45 (0.00%) 
Nervous system disorders     
Neuropathy peripheral * 1  22/46 (47.83%)  0/45 (0.00%) 
Paraesthesia * 1  11/46 (23.91%)  2/45 (4.44%) 
Headache * 1  7/46 (15.22%)  2/45 (4.44%) 
Dysaesthesia * 1  4/46 (8.70%)  0/45 (0.00%) 
Renal and urinary disorders     
Proteinuria * 1  20/46 (43.48%)  13/45 (28.89%) 
Dysuria * 1  12/46 (26.09%)  10/45 (22.22%) 
Pollakiuria * 1  2/46 (4.35%)  3/45 (6.67%) 
Reproductive system and breast disorders     
Erectile dysfunction * 1  3/46 (6.52%)  1/45 (2.22%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  15/46 (32.61%)  2/45 (4.44%) 
Skin and subcutaneous tissue disorders     
Palmar-plantar erythrodysaesthesia syndrome * 1  4/46 (8.70%)  0/45 (0.00%) 
Alopecia * 1  3/46 (6.52%)  0/45 (0.00%) 
Pruritus * 1  3/46 (6.52%)  0/45 (0.00%) 
Vascular disorders     
Hypertension * 1  11/46 (23.91%)  7/45 (15.56%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00865189     History of Changes
Other Study ID Numbers: ML19202
2006-003472-35 ( EudraCT Number )
First Submitted: March 18, 2009
First Posted: March 19, 2009
Results First Submitted: April 13, 2017
Results First Posted: August 4, 2017
Last Update Posted: August 4, 2017