Trial Outcomes & Findings for Bevacizumab and Cetuximab in Combination With FOLFOX6 in Patients With Metastatic Colorectal Cancer (NCT NCT00193219)
NCT ID: NCT00193219
Last Updated: 2022-01-11
Results Overview
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
36 participants
Primary outcome timeframe
18 months
Results posted on
2022-01-11
Participant Flow
Participant milestones
| Measure |
Bevacizumab/Cetuximab/FOLFOX
Bevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
|
|---|---|
|
Overall Study
STARTED
|
36
|
|
Overall Study
COMPLETED
|
6
|
|
Overall Study
NOT COMPLETED
|
30
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bevacizumab and Cetuximab in Combination With FOLFOX6 in Patients With Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Bevacizumab/Cetuximab/FOLFOX
n=36 Participants
Bevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
|
|---|---|
|
Age, Continuous
|
55 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
36 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: This study was originally designed as a randomized study with patients receiving FOLFOX and bevacizumab with or without cetuximab. Following an amendment, all patients received cetuximab, FOLFOX and bevacizumab. The 5 patients randomized prior to the amendment that did not receive cetuximab are excluded from the analysis.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Bevacizumab/Cetuximab/FOLFOX
n=31 Participants
Bevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
|
|---|---|
|
Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
|
55 percentage of patients
Interval 36.0 to 73.0
|
SECONDARY outcome
Timeframe: 18 monthsPopulation: This study was originally designed as a randomized study with patients receiving FOLFOX and bevacizumab with or without cetuximab. Following an amendment, all patients received cetuximab, FOLFOX and bevacizumab. The 5 patients randomized prior to the amendment that did not receive cetuximab are excluded from the analysis.
Progression Free Survival (PFS) is defined as the interval between the start date of treatment and the date of occurrence of progressive disease or death.
Outcome measures
| Measure |
Bevacizumab/Cetuximab/FOLFOX
n=31 Participants
Bevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
|
|---|---|
|
Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease
|
9 months
Interval 8.3 to 15.2
|
SECONDARY outcome
Timeframe: 36 monthsPopulation: This study was originally designed as a randomized study with patients receiving FOLFOX and bevacizumab with or without cetuximab. Following an amendment, all patients received cetuximab, FOLFOX and bevacizumab. The 5 patients randomized prior to the amendment that did not receive cetuximab are excluded from the analysis.
Measured from the date of first treatment until the date of death from any cause
Outcome measures
| Measure |
Bevacizumab/Cetuximab/FOLFOX
n=31 Participants
Bevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
|
|---|---|
|
Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
|
25.7 months
Interval 15.4 to 27.6
|
SECONDARY outcome
Timeframe: 18 monthsPopulation: This study was originally designed as a randomized study with patients receiving FOLFOX and bevacizumab with or without cetuximab. Following an amendment, all patients received cetuximab, FOLFOX and bevacizumab. The 5 patients randomized prior to the amendment that did not receive cetuximab are excluded from the analysis.
The toxicity assessments were made according to the common terminology criteria for adverse events (CTCAE version 3.0) of the National Cancer Institute. Number of participants with Grade 1 to 5 adverse events are reported here.
Outcome measures
| Measure |
Bevacizumab/Cetuximab/FOLFOX
n=31 Participants
Bevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
|
|---|---|
|
Number of Patients With Adverse Events as a Measure of Safety With FOLFOX6 Combined With Bevacizumab and Cetuximab
|
31 Participants
|
Adverse Events
Bevacizumab/Cetuximab/FOLFOX
Serious events: 14 serious events
Other events: 31 other events
Deaths: 0 deaths
Bevacizumab/FOLFOX
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bevacizumab/Cetuximab/FOLFOX
n=31 participants at risk
Bevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
|
Bevacizumab/FOLFOX
n=5 participants at risk
Bevacizumab 5 mg/kg IV; Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient); Leucovorin 350 mg IV; Oxaliplatin 85 mg/m2 IV
|
|---|---|---|
|
Gastrointestinal disorders
Pain - Gastrointestinal
|
6.5%
2/31 • Number of events 2
|
0.00%
0/5
|
|
Vascular disorders
Thrombosis/Thrombus/Embolism
|
12.9%
4/31 • Number of events 4
|
0.00%
0/5
|
|
Gastrointestinal disorders
Hemorrhage
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Gastrointestinal disorders
Dehydration
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
ARDS
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Nervous system disorders
Mental Status
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Gastrointestinal disorders
Pain - Abdominal
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Progressive Disease
|
9.7%
3/31 • Number of events 3
|
0.00%
0/5
|
|
Renal and urinary disorders
Pain - Renal/Genitourinary
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Psychiatric disorders
Dementia
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Eye disorders
Blurred Vision
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Gastrointestinal disorders
Diarrhea
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Infections and infestations
Sepsis
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Vascular disorders
Venous Occlusion
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Immune system disorders
Allergic Reaction
|
6.5%
2/31 • Number of events 2
|
0.00%
0/5
|
|
Infections and infestations
Febrile Neutropenia
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
General disorders
Multi Organ Failure
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Surgical and medical procedures
Chemoport Malfunction
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Gastrointestinal disorders
Acute Appendicitis
|
3.2%
1/31 • Number of events 1
|
0.00%
0/5
|
|
Ear and labyrinth disorders
Hearing loss
|
0.00%
0/31
|
20.0%
1/5 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary infiltrates
|
0.00%
0/31
|
20.0%
1/5 • Number of events 1
|
Other adverse events
| Measure |
Bevacizumab/Cetuximab/FOLFOX
n=31 participants at risk
Bevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV
|
Bevacizumab/FOLFOX
n=5 participants at risk
Bevacizumab 5 mg/kg IV; Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient); Leucovorin 350 mg IV; Oxaliplatin 85 mg/m2 IV
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Alopecia
|
35.5%
11/31 • Number of events 54
|
20.0%
1/5 • Number of events 1
|
|
Nervous system disorders
Altered Mental Status
|
6.5%
2/31 • Number of events 3
|
0.00%
0/5
|
|
Blood and lymphatic system disorders
Anemia
|
61.3%
19/31 • Number of events 105
|
60.0%
3/5 • Number of events 45
|
|
Gastrointestinal disorders
Anorexia
|
71.0%
22/31 • Number of events 83
|
20.0%
1/5 • Number of events 4
|
|
Psychiatric disorders
Anxiety
|
9.7%
3/31 • Number of events 6
|
20.0%
1/5 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
22.6%
7/31 • Number of events 13
|
20.0%
1/5 • Number of events 1
|
|
Eye disorders
Blurred Vision
|
6.5%
2/31 • Number of events 4
|
0.00%
0/5
|
|
General disorders
Chills
|
12.9%
4/31 • Number of events 8
|
0.00%
0/5
|
|
General disorders
Cold Sensitivity
|
25.8%
8/31 • Number of events 36
|
40.0%
2/5 • Number of events 4
|
|
Nervous system disorders
Confusion
|
6.5%
2/31 • Number of events 3
|
0.00%
0/5
|
|
Gastrointestinal disorders
Constipation
|
45.2%
14/31 • Number of events 52
|
40.0%
2/5 • Number of events 7
|
|
Gastrointestinal disorders
Cramps (abdominal)
|
6.5%
2/31 • Number of events 3
|
0.00%
0/5
|
|
Blood and lymphatic system disorders
Deep Vein Thrombosis
|
9.7%
3/31 • Number of events 21
|
0.00%
0/5
|
|
Gastrointestinal disorders
Dehydration
|
9.7%
3/31 • Number of events 4
|
0.00%
0/5
|
|
Psychiatric disorders
Depression
|
12.9%
4/31 • Number of events 6
|
20.0%
1/5 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhea
|
71.0%
22/31 • Number of events 112
|
60.0%
3/5 • Number of events 14
|
|
Nervous system disorders
Dizziness
|
6.5%
2/31 • Number of events 2
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
9.7%
3/31 • Number of events 8
|
0.00%
0/5
|
|
Renal and urinary disorders
Dysuria
|
9.7%
3/31 • Number of events 5
|
0.00%
0/5
|
|
Blood and lymphatic system disorders
Edema
|
25.8%
8/31 • Number of events 21
|
0.00%
0/5
|
|
Hepatobiliary disorders
Elevated AST
|
6.5%
2/31 • Number of events 3
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.5%
2/31 • Number of events 3
|
40.0%
2/5 • Number of events 6
|
|
Infections and infestations
Esophagitis
|
9.7%
3/31 • Number of events 5
|
0.00%
0/5
|
|
General disorders
Fatigue
|
96.8%
30/31 • Number of events 248
|
100.0%
5/5 • Number of events 37
|
|
Infections and infestations
Febrile Neutropenia
|
9.7%
3/31 • Number of events 7
|
0.00%
0/5
|
|
General disorders
Fever
|
19.4%
6/31 • Number of events 9
|
20.0%
1/5 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Fingertip Fissures
|
6.5%
2/31 • Number of events 12
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Flu Syndrome
|
0.00%
0/31
|
20.0%
1/5 • Number of events 3
|
|
Gastrointestinal disorders
Hemorrhoids
|
12.9%
4/31 • Number of events 15
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Hiccoughs
|
0.00%
0/31
|
20.0%
1/5 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
35.5%
11/31 • Number of events 36
|
0.00%
0/5
|
|
General disorders
Hypersensitivity Reaction
|
16.1%
5/31 • Number of events 5
|
20.0%
1/5 • Number of events 12
|
|
Cardiac disorders
Hypertension
|
6.5%
2/31 • Number of events 4
|
20.0%
1/5 • Number of events 6
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
6.5%
2/31 • Number of events 8
|
0.00%
0/5
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
6.5%
2/31 • Number of events 3
|
0.00%
0/5
|
|
Metabolism and nutrition disorders
Hypokalemia
|
12.9%
4/31 • Number of events 6
|
0.00%
0/5
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
9.7%
3/31 • Number of events 10
|
0.00%
0/5
|
|
Gastrointestinal disorders
Indigestion
|
6.5%
2/31 • Number of events 2
|
0.00%
0/5
|
|
Infections and infestations
Infection
|
6.5%
2/31 • Number of events 2
|
0.00%
0/5
|
|
General disorders
Insomnia
|
22.6%
7/31 • Number of events 13
|
40.0%
2/5 • Number of events 22
|
|
Blood and lymphatic system disorders
leukopenia
|
61.3%
19/31 • Number of events 76
|
0.00%
0/5
|
|
Nervous system disorders
Motor Neuropathy
|
0.00%
0/31
|
20.0%
1/5 • Number of events 8
|
|
Gastrointestinal disorders
Mucositis
|
41.9%
13/31 • Number of events 35
|
40.0%
2/5 • Number of events 12
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.7%
3/31 • Number of events 3
|
0.00%
0/5
|
|
Skin and subcutaneous tissue disorders
Nail Changes
|
12.9%
4/31 • Number of events 16
|
20.0%
1/5 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
77.4%
24/31 • Number of events 75
|
40.0%
2/5 • Number of events 18
|
|
Blood and lymphatic system disorders
Neutropenia
|
80.6%
25/31 • Number of events 92
|
80.0%
4/5 • Number of events 34
|
|
General disorders
Night Sweats
|
0.00%
0/31
|
20.0%
1/5 • Number of events 3
|
|
General disorders
Pain
|
64.5%
20/31 • Number of events 80
|
60.0%
3/5 • Number of events 16
|
|
Skin and subcutaneous tissue disorders
palmar plantar erythrodysesthesia
|
16.1%
5/31 • Number of events 16
|
0.00%
0/5
|
|
Metabolism and nutrition disorders
Proteinuria
|
38.7%
12/31 • Number of events 30
|
20.0%
1/5 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
16.1%
5/31 • Number of events 12
|
0.00%
0/5
|
|
Gastrointestinal disorders
reflux
|
6.5%
2/31 • Number of events 7
|
0.00%
0/5
|
|
Nervous system disorders
Sensory Neuropathy
|
64.5%
20/31 • Number of events 136
|
60.0%
3/5 • Number of events 36
|
|
Respiratory, thoracic and mediastinal disorders
Sinus Drainage
|
6.5%
2/31 • Number of events 2
|
0.00%
0/5
|
|
Infections and infestations
sinus infection
|
6.5%
2/31 • Number of events 2
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Sore Throat
|
12.9%
4/31 • Number of events 17
|
0.00%
0/5
|
|
Gastrointestinal disorders
Taste Alteration
|
22.6%
7/31 • Number of events 19
|
0.00%
0/5
|
|
Blood and lymphatic system disorders
thrombocytopenia
|
61.3%
19/31 • Number of events 78
|
0.00%
0/5
|
|
Gastrointestinal disorders
Vomiting
|
45.2%
14/31 • Number of events 28
|
40.0%
2/5 • Number of events 3
|
|
General disorders
Weakness
|
22.6%
7/31 • Number of events 34
|
0.00%
0/5
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
- Publication restrictions are in place
Restriction type: OTHER