Combination Chemotherapy With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for High Risk Stage II or Stage III Colon Cancer
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Study Type: | Interventional |
|---|---|
| Study Design: | Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment |
| Condition: |
Colorectal Cancer |
| Interventions: |
Biological: Bevacizumab Drug: Capecitabine Drug: 5-Fluorouracil (5-FU) Drug: Leucovorin calcium Drug: Oxaliplatin |
Participant Flow
Recruitment Details
| Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations |
|---|
| No text entered. |
Pre-Assignment Details
| Significant events and approaches for the overall study following participant enrollment, but prior to group assignment |
|---|
| Randomization was stratified according to geographic region and disease stage (high-risk stage II or stage III N1 or stage III N2). The primary analysis population consisted of patients with Stage III disease. |
Reporting Groups
| Description | |
|---|---|
| FOLFOX4 |
Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-fluorouracil (5-FU), given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Observation only. |
| FOLFOX4 + Bv |
Weeks 1–24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 – 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25–48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks). |
| XELOX+Bv |
Weeks 1–24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 – 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks). Weeks 25–48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks). |
Participant Flow: Overall Study
| FOLFOX4 | FOLFOX4 + Bv | XELOX+Bv | |
|---|---|---|---|
| STARTED | 1151 | 1155 | 1145 |
| Received Treatment | 1126 | 1145 [1] | 1135 |
| Stage III Disease Population | 955 | 960 | 952 |
| COMPLETED | 937 [2] | 917 [2] | 916 [2] |
| NOT COMPLETED | 214 | 238 | 229 |
| [1] | Includes two patients from FOLFOX4 who received Bv and were assigned to FOLFOX4+Bv safety analysis |
|---|---|
| [2] | Represents patients alive in follow-up at the time of data cut-off (30 June 2010) |
Baseline Characteristics
Reporting Groups
| Description | |
|---|---|
| FOLFOX4 |
Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-fluorouracil (5-FU), given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Observation only. |
| FOLFOX4 + Bv |
Weeks 1–24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 – 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25–48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks). |
| XELOX+Bv |
Weeks 1–24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 – 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks). Weeks 25–48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks). |
| Total | Total of all reporting groups |
Baseline Measures
| FOLFOX4 | FOLFOX4 + Bv | XELOX+Bv | Total | |
|---|---|---|---|---|
|
Number of Participants
[units: participants] |
955 | 960 | 952 | 2867 |
|
Age, Customized
[1] [units: participants] |
||||
| <40 | 77 | 74 | 68 | 219 |
| 40-65 | 603 | 625 | 588 | 1816 |
| >=65 | 275 | 261 | 296 | 832 |
|
Gender
[units: participants] |
||||
| Female | 425 | 473 | 432 | 1330 |
| Male | 530 | 487 | 520 | 1537 |
|
Race/Ethnicity, Customized
[units: participants] |
||||
| American Indian or Alaska Native | 1 | 1 | 0 | 2 |
| Asian | 139 | 115 | 123 | 377 |
| Black or African American | 6 | 13 | 14 | 33 |
| White | 791 | 813 | 795 | 2399 |
| Other | 18 | 18 | 20 | 56 |
| [1] | Baseline Measures are based on the Intent-to-Treat - Stage III Disease Patient Population. |
|---|
Outcome Measures
| 1. Primary: | Disease-free Survival in Stage III Cancer Patients - Time to Event [ Time Frame: From first patient randomized until the data cut-off date of 30 June 2010 (36 months after the last patient randomized). ] |
| 2. Primary: | Disease-free Survival in Stage III Cancer Patients - Number of Events [ Time Frame: From first patient randomized until the data cut-off date of 30 June 2010 (36 months after the last patient randomized). ] |
| 3. Secondary: | Overall Survival in Stage III Cancer Patients - Time to Event [ Time Frame: From first patient randomized until the clinical data cut-off date of 30 June 2010 (36 months after the last patient randomized). ] |
| 4. Secondary: | Overall Survival in Stage III Cancer Patients - Number of Events [ Time Frame: From first patient randomized until the clinical data cut-off date of 30 June 2010 (36 months after the last patient randomized). ] |
Serious Adverse Events Other Adverse Events
| Time Frame | All adverse events occurring between the date of first drug intake and 28 days after last drug intake, regardless of which treatment group the patient was randomized to. |
|---|---|
| Additional Description | No text entered. |
Frequency Threshold
| Threshold above which other adverse events are reported | 5% |
|---|
Reporting Groups
| Description | |
|---|---|
| FOLFOX4 |
Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with Leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Observation only. |
| FOLFOX4 + Bv |
Weeks 1–24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 – 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25–48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks). |
| XELOX+Bv |
Weeks 1–24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 – 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks). Weeks 25–48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks). |
Other Adverse Events
| FOLFOX4 | FOLFOX4 + Bv | XELOX+Bv | |
|---|---|---|---|
| Total, other (not including serious) adverse events | |||
| # participants affected / at risk | 1112/1126 | 1127/1145 | 1117/1135 |
| Blood and lymphatic system disorders | |||
| Neutropenia † 1 | |||
| # participants affected / at risk | 660/1126 (58.61%) | 567/1145 (49.52%) | 273/1135 (24.05%) |
| Thrombocytopenia † 1 | |||
| # participants affected / at risk | 331/1126 (29.40%) | 115/1145 (10.04%) | 99/1135 (8.72%) |
| Anaemia † 1 | |||
| # participants affected / at risk | 116/1126 (10.30%) | 89/1145 (7.77%) | 74/1135 (6.52%) |
| Leukopenia † 1 | |||
| # participants affected / at risk | 79/1126 (7.02%) | 55/1145 (4.80%) | 34/1135 (3.00%) |
| Eye disorders | |||
| Lacrimation increased † 1 | |||
| # participants affected / at risk | 70/1126 (6.22%) | 69/1145 (6.03%) | 35/1135 (3.08%) |
| Gastrointestinal disorders | |||
| Nausea † 1 | |||
| # participants affected / at risk | 725/1126 (64.39%) | 761/1145 (66.46%) | 720/1135 (63.44%) |
| Diarrhoea † 1 | |||
| # participants affected / at risk | 620/1126 (55.06%) | 699/1145 (61.05%) | 699/1135 (61.59%) |
| Vomiting † 1 | |||
| # participants affected / at risk | 385/1126 (34.19%) | 394/1145 (34.41%) | 460/1135 (40.53%) |
| Stomatitis † 1 | |||
| # participants affected / at risk | 310/1126 (27.53%) | 360/1145 (31.44%) | 246/1135 (21.67%) |
| Constipation † 1 | |||
| # participants affected / at risk | 308/1126 (27.35%) | 324/1145 (28.30%) | 219/1135 (19.30%) |
| Abdominal pain † 1 | |||
| # participants affected / at risk | 220/1126 (19.54%) | 227/1145 (19.83%) | 214/1135 (18.85%) |
| Dyspepsia † 1 | |||
| # participants affected / at risk | 126/1126 (11.19%) | 162/1145 (14.15%) | 84/1135 (7.40%) |
| Abdominal pain upper † 1 | |||
| # participants affected / at risk | 86/1126 (7.64%) | 118/1145 (10.31%) | 113/1135 (9.96%) |
| Haemorrhoids † 1 | |||
| # participants affected / at risk | 29/1126 (2.58%) | 68/1145 (5.94%) | 41/1135 (3.61%) |
| General disorders | |||
| Fatigue † 1 | |||
| # participants affected / at risk | 404/1126 (35.88%) | 425/1145 (37.12%) | 355/1135 (31.28%) |
| Asthenia † 1 | |||
| # participants affected / at risk | 241/1126 (21.40%) | 251/1145 (21.92%) | 250/1135 (22.03%) |
| Pyrexia † 1 | |||
| # participants affected / at risk | 186/1126 (16.52%) | 185/1145 (16.16%) | 106/1135 (9.34%) |
| Mucosal inflammation † 1 | |||
| # participants affected / at risk | 85/1126 (7.55%) | 85/1145 (7.42%) | 57/1135 (5.02%) |
| Temperature intolerance † 1 | |||
| # participants affected / at risk | 61/1126 (5.42%) | 61/1145 (5.33%) | 50/1135 (4.41%) |
| Oedema peripheral † 1 | |||
| # participants affected / at risk | 54/1126 (4.80%) | 62/1145 (5.41%) | 45/1135 (3.96%) |
| Immune system disorders | |||
| Drug hypersensitivity † 1 | |||
| # participants affected / at risk | 66/1126 (5.86%) | 72/1145 (6.29%) | 32/1135 (2.82%) |
| Infections and infestations | |||
| Nasopharyngitis † 1 | |||
| # participants affected / at risk | 76/1126 (6.75%) | 92/1145 (8.03%) | 70/1135 (6.17%) |
| Upper respiratory tract infection † 1 | |||
| # participants affected / at risk | 52/1126 (4.62%) | 87/1145 (7.60%) | 55/1135 (4.85%) |
| Investigations | |||
| Weight increased † 1 | |||
| # participants affected / at risk | 58/1126 (5.15%) | 81/1145 (7.07%) | 68/1135 (5.99%) |
| Weight decreased † 1 | |||
| # participants affected / at risk | 26/1126 (2.31%) | 56/1145 (4.89%) | 61/1135 (5.37%) |
| Metabolism and nutrition disorders | |||
| Decreased appetite † 1 | |||
| # participants affected / at risk | 268/1126 (23.80%) | 324/1145 (28.30%) | 295/1135 (25.99%) |
| Musculoskeletal and connective tissue disorders | |||
| Arthralgia † 1 | |||
| # participants affected / at risk | 63/1126 (5.60%) | 140/1145 (12.23%) | 122/1135 (10.75%) |
| Pain in extremity † 1 | |||
| # participants affected / at risk | 63/1126 (5.60%) | 78/1145 (6.81%) | 116/1135 (10.22%) |
| Back pain † 1 | |||
| # participants affected / at risk | 79/1126 (7.02%) | 87/1145 (7.60%) | 66/1135 (5.81%) |
| Musculoskeletal pain † 1 | |||
| # participants affected / at risk | 35/1126 (3.11%) | 86/1145 (7.51%) | 46/1135 (4.05%) |
| Myalgia † 1 | |||
| # participants affected / at risk | 39/1126 (3.46%) | 70/1145 (6.11%) | 56/1135 (4.93%) |
| Nervous system disorders | |||
| Peripheral sensory neuropathy † 1 | |||
| # participants affected / at risk | 430/1126 (38.19%) | 430/1145 (37.55%) | 436/1135 (38.41%) |
| Paraesthesia † 1 | |||
| # participants affected / at risk | 310/1126 (27.53%) | 328/1145 (28.65%) | 314/1135 (27.67%) |
| Neuropathy peripheral † 1 | |||
| # participants affected / at risk | 252/1126 (22.38%) | 234/1145 (20.44%) | 204/1135 (17.97%) |
| Headache † 1 | |||
| # participants affected / at risk | 169/1126 (15.01%) | 284/1145 (24.80%) | 219/1135 (19.30%) |
| Dysgeusia † 1 | |||
| # participants affected / at risk | 237/1126 (21.05%) | 222/1145 (19.39%) | 152/1135 (13.39%) |
| Dysaesthesia † 1 | |||
| # participants affected / at risk | 128/1126 (11.37%) | 106/1145 (9.26%) | 128/1135 (11.28%) |
| Dizziness † 1 | |||
| # participants affected / at risk | 102/1126 (9.06%) | 117/1145 (10.22%) | 79/1135 (6.96%) |
| Neurotoxicity † 1 | |||
| # participants affected / at risk | 60/1126 (5.33%) | 69/1145 (6.03%) | 50/1135 (4.41%) |
| Lethargy † 1 | |||
| # participants affected / at risk | 44/1126 (3.91%) | 50/1145 (4.37%) | 59/1135 (5.20%) |
| Psychiatric disorders | |||
| Insomnia † 1 | |||
| # participants affected / at risk | 135/1126 (11.99%) | 132/1145 (11.53%) | 91/1135 (8.02%) |
| Anxiety † 1 | |||
| # participants affected / at risk | 45/1126 (4.00%) | 60/1145 (5.24%) | 61/1135 (5.37%) |
| Renal and urinary disorders | |||
| Proteinuria † 1 | |||
| # participants affected / at risk | 19/1126 (1.69%) | 73/1145 (6.38%) | 69/1135 (6.08%) |
| Respiratory, thoracic and mediastinal disorders | |||
| Epistaxis † 1 | |||
| # participants affected / at risk | 228/1126 (20.25%) | 424/1145 (37.03%) | 216/1135 (19.03%) |
| Cough † 1 | |||
| # participants affected / at risk | 86/1126 (7.64%) | 120/1145 (10.48%) | 41/1135 (3.61%) |
| Dyspnoea † 1 | |||
| # participants affected / at risk | 57/1126 (5.06%) | 74/1145 (6.46%) | 73/1135 (6.43%) |
| Dysphonia † 1 | |||
| # participants affected / at risk | 17/1126 (1.51%) | 91/1145 (7.95%) | 74/1135 (6.52%) |
| Dysaesthesia pharynx † 1 | |||
| # participants affected / at risk | 37/1126 (3.29%) | 28/1145 (2.45%) | 79/1135 (6.96%) |
| Oropharyngeal pain † 1 | |||
| # participants affected / at risk | 52/1126 (4.62%) | 59/1145 (5.15%) | 33/1135 (2.91%) |
| Skin and subcutaneous tissue disorders | |||
| Palmar-Plantar Erythrodysaesthesia Syndrome † 1 | |||
| # participants affected / at risk | 98/1126 (8.70%) | 119/1145 (10.39%) | 435/1135 (38.33%) |
| Alopecia † 1 | |||
| # participants affected / at risk | 231/1126 (20.52%) | 241/1145 (21.05%) | 73/1135 (6.43%) |
| Rash † 1 | |||
| # participants affected / at risk | 114/1126 (10.12%) | 112/1145 (9.78%) | 110/1135 (9.69%) |
| Dry skin † 1 | |||
| # participants affected / at risk | 52/1126 (4.62%) | 66/1145 (5.76%) | 50/1135 (4.41%) |
| Pruritus † 1 | |||
| # participants affected / at risk | 36/1126 (3.20%) | 65/1145 (5.68%) | 28/1135 (2.47%) |
| Vascular disorders | |||
| Hypertension † 1 | |||
| # participants affected / at risk | 196/1126 (17.41%) | 472/1145 (41.22%) | 468/1135 (41.23%) |
| † | Events were collected by systematic assessment |
|---|---|
| 1 | Term from vocabulary, MedDRA (13.0) |