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S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00946712
Recruitment Status : Active, not recruiting
First Posted : July 27, 2009
Results First Posted : March 7, 2019
Last Update Posted : May 19, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Recurrent Large Cell Lung Carcinoma
Recurrent Lung Adenocarcinoma
Recurrent Squamous Cell Lung Carcinoma
Stage IV Large Cell Lung Carcinoma
Stage IV Lung Adenocarcinoma
Stage IV Squamous Cell Lung Carcinoma
Interventions Biological: Bevacizumab
Drug: Carboplatin
Biological: Cetuximab
Other: Laboratory Biomarker Analysis
Drug: Paclitaxel
Enrollment 1333
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm I (Chemo +/- Bevacizumab) Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Hide Arm/Group Description

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Patients receive paclitaxel and carboplatin with or without bevacizumab as in Arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Cetuximab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Period Title: Overall Study
Started 671 662
Completed 124 0
Not Completed 547 662
Reason Not Completed
Adverse Event             118             124
Disease progression             308             404
Death             21             22
No treatment given             25             29
Other reasons             61             73
On Treatment             0             4
Ineligible             14             6
Arm/Group Title Arm I (Chemo +/- Bevacizumab) Arm II (Chemo, Cetuximab, +/- Bevacizumab) Total
Hide Arm/Group Description

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Patients receive paclitaxel and carboplatin with or without bevacizumab as in Arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Cetuximab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Total of all reporting groups
Overall Number of Baseline Participants 657 656 1313
Hide Baseline Analysis Population Description
Only eligible patients are included in the analysis.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 657 participants 656 participants 1313 participants
63
(30 to 86)
63
(19 to 84)
63
(19 to 86)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Age, Categorized Number Analyzed 657 participants 656 participants 1313 participants
Age <= 65
379
  57.7%
381
  58.1%
760
  57.9%
Age > 65
278
  42.3%
275
  41.9%
553
  42.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 657 participants 656 participants 1313 participants
Female
298
  45.4%
271
  41.3%
569
  43.3%
Male
359
  54.6%
385
  58.7%
744
  56.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 657 participants 656 participants 1313 participants
Hispanic or Latino
26
   4.0%
16
   2.4%
42
   3.2%
Not Hispanic or Latino
606
  92.2%
618
  94.2%
1224
  93.2%
Unknown or Not Reported
25
   3.8%
22
   3.4%
47
   3.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 657 participants 656 participants 1313 participants
White
565
  86.0%
568
  86.6%
1133
  86.3%
Black
61
   9.3%
55
   8.4%
116
   8.8%
Asian
10
   1.5%
18
   2.7%
28
   2.1%
Pacific Islander
3
   0.5%
6
   0.9%
9
   0.7%
Native American
2
   0.3%
1
   0.2%
3
   0.2%
Unknown
16
   2.4%
8
   1.2%
24
   1.8%
M-stage   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 657 participants 656 participants 1313 participants
M1a
148
  22.5%
150
  22.9%
298
  22.7%
M1b
509
  77.5%
506
  77.1%
1015
  77.3%
[1]
Measure Description:

M staging per AJCC Cancer Staging Manual, 7th Edition, 2009. M1a: Separate tumor nodule(s) in a contralateral lobe; tumor with pleural nodules or malignant pleural (or pericardial) effusion.

M1b: Distant metastases

Bevacizumab treatment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 657 participants 656 participants 1313 participants
Yes
277
  42.2%
283
  43.1%
560
  42.7%
No
380
  57.8%
373
  56.9%
753
  57.3%
Smoking History  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 657 participants 656 participants 1313 participants
Current
297
  45.2%
292
  44.5%
589
  44.9%
Former
303
  46.1%
305
  46.5%
608
  46.3%
Never
57
   8.7%
59
   9.0%
116
   8.8%
Histology   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 657 participants 656 participants 1313 participants
Squamous cell carcinoma
161
  24.5%
160
  24.4%
321
  24.4%
Adenocarcinoma
408
  62.1%
411
  62.7%
819
  62.4%
Other
88
  13.4%
85
  13.0%
173
  13.2%
[1]
Measure Description: 'Other' includes large-cell carcinoma, bronchioloalveolar carcinoma, mixed, other, and not reported.
Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 657 participants 656 participants 1313 participants
0
229
  34.9%
256
  39.0%
485
  36.9%
1
427
  65.0%
400
  61.0%
827
  63.0%
Missing Data
1
   0.2%
0
   0.0%
1
   0.1%
[1]
Measure Description:

Patients will be graded according to the Zubrod Performance Status Scale. 0 Fully active, able to carry on all pre-disease performance without restriction.

1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.

EGFR (Epidermal Growth Factor Receptor) FISH (Fluorescence In Situ Hybridization) status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 657 participants 656 participants 1313 participants
Positive
201
  30.6%
199
  30.3%
400
  30.5%
Negative
293
  44.6%
283
  43.1%
576
  43.9%
Unknown
163
  24.8%
174
  26.5%
337
  25.7%
1.Primary Outcome
Title Overall Survival (OS) in the Entire Study Population
Hide Description From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time Frame Patients will be followed every 3 weeks while on protocol treatment. Once off all protocol treatment, patients will be followed every 6 months until death or up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients are included in the analysis.
Arm/Group Title Arm I (Chemo +/- Bevacizumab) Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Hide Arm/Group Description:

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Patients receive paclitaxel and carboplatin with or without bevacizumab as in Arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Cetuximab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Overall Number of Participants Analyzed 657 656
Median (95% Confidence Interval)
Unit of Measure: months
9.2
(8.7 to 10.3)
10.9
(9.5 to 12.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (Chemo +/- Bevacizumab), Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method Log Rank
Comments A stratified log rank test was used.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.83 to 1.04
Estimation Comments [Not Specified]
2.Primary Outcome
Title Progression-free Survival (PFS) of EGFR FISH-positive Patients by Institutional Review
Hide Description From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, whichever comes first by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as assessed by the treating investigator.Patients last known to be alive and progression-free are censored at date of last contact. Progression is defined using RECIST 1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame Disease assessment will be repeated every 6 weeks for the first 9 months and every 3 months thereafter, until disease progression.
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients with EGFR FISH positive are included in the analysis.
Arm/Group Title Arm I (Chemo +/- Bevacizumab) Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Hide Arm/Group Description:

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Patients receive paclitaxel and carboplatin with or without bevacizumab as in Arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Cetuximab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Overall Number of Participants Analyzed 201 199
Median (95% Confidence Interval)
Unit of Measure: months
4.8
(3.9 to 5.5)
5.4
(4.5 to 5.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (Chemo +/- Bevacizumab), Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments [Not Specified]
Method Log Rank
Comments A stratified log rank test was used.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.75 to 1.12
Estimation Comments [Not Specified]
3.Secondary Outcome
Title OS of EGFR FISH-positive Patients by Centralized Review
Hide Description From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time Frame Patients will be followed every 3 weeks while on protocol treatment. Once off all protocol treatment, patients will be followed every 6 months until death or up to 3 years
Outcome Measure Data Not Reported
4.Secondary Outcome
Title PFS of EGFR FISH-positive Patients by Centralized Review
Hide Description From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, whichever comes first by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as assessed by the treating investigator.Patients last known to be alive and progression-free are censored at date of last contact. Progression is defined using RECIST 1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame Disease assessment will be repeated every 6 weeks until disease progression while on treatment. After off treatment, the frequency of disease assessment may be reduced to every 3 months until disease progression.
Outcome Measure Data Not Reported
5.Secondary Outcome
Title PFS of the Entire Study Population by Centralized Review and by Institutional Review
Hide Description From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, whichever comes first by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as assessed by the treating investigator.Patients last known to be alive and progression-free are censored at date of last contact. Progression is defined using RECIST 1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame Disease assessment will be repeated every 6 weeks until disease progression while on treatment. After off treatment, the frequency of disease assessment may be reduced to every 3 months until disease progression.
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Response Rate (Confirmed Plus Unconfirmed, Complete and Partial Responses) in the Subset of Patients With Measurable Disease in EGFR FISH-positive Patients
Hide Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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
Time Frame Disease assessment will be repeated every 6 weeks for the first 9 months and every 3 months thereafter, until disease progression.
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible EGFR FISH positive patients with baseline measurable disease are included in the analysis.
Arm/Group Title Arm I (Chemo +/- Bevacizumab) Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Hide Arm/Group Description:

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Patients receive paclitaxel and carboplatin with or without bevacizumab as in Arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Cetuximab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Overall Number of Participants Analyzed 191 187
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of analyzed participants
43
(36 to 50)
47
(39 to 54)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (Chemo +/- Bevacizumab), Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments A stratified Cochran-Mantel-Haenszel test was conducted.
7.Secondary Outcome
Title Response Rate (Confirmed Plus Unconfirmed, Complete and Partial Responses) in the Subset of Patients With Measurable Disease in the Entire Study Population
Hide Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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.
Time Frame Disease assessment will be repeated every 6 weeks for the first 9 months and every 3 months thereafter, until disease progression.
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients with baseline measurable disease are included in the analysis.
Arm/Group Title Arm I (Chemo +/- Bevacizumab) Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Hide Arm/Group Description:

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Patients receive paclitaxel and carboplatin with or without bevacizumab as in Arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Cetuximab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Overall Number of Participants Analyzed 623 617
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of analyzed participants
36
(33 to 40)
42
(38 to 46)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (Chemo +/- Bevacizumab), Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.060
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments A stratified Cochran-Mantel-Haenszel test was conducted.
8.Secondary Outcome
Title Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Hide Description Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time Frame Toxicity assessment was evaluated every 3 weeks while one protocol treatment. Chemo and cetuximab is treated for 6 cycles (1 cycle =3 weeks) and Bevacizumab is treated until progression or unacceptable toxicity.
Hide Outcome Measure Data
Hide Analysis Population Description
Limited to eligible patients who started treatment, who did not have a major deviation in the treatment protocol, and whose toxicity profile has been completed.
Arm/Group Title Arm I (Chemo +/- Bevacizumab) Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Hide Arm/Group Description:

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Patients receive paclitaxel and carboplatin with or without bevacizumab as in Arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Cetuximab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Overall Number of Participants Analyzed 632 627
Measure Type: Count of Participants
Unit of Measure: Participants
ALT, SGPT (serum glutamic pyruvic transaminase)
5
   0.8%
8
   1.3%
AST, SGOT
6
   0.9%
8
   1.3%
Acidosis (metabolic or respiratory)
0
   0.0%
1
   0.2%
Adrenal insufficiency
0
   0.0%
1
   0.2%
Albumin, serum-low (hypoalbuminemia)
8
   1.3%
7
   1.1%
Alkaline phosphatase
2
   0.3%
1
   0.2%
Allergic reaction/hypersensitivity
9
   1.4%
41
   6.5%
Allergy/Immunology-Other (Specify)
0
   0.0%
2
   0.3%
Anorexia
22
   3.5%
25
   4.0%
Apnea
0
   0.0%
1
   0.2%
Aspiration
0
   0.0%
2
   0.3%
Ataxia (incoordination)
1
   0.2%
0
   0.0%
Bilirubin (hyperbilirubinemia)
2
   0.3%
0
   0.0%
Blood/Bone Marrow-Other (Specify)
2
   0.3%
3
   0.5%
Bronchospasm, wheezing
0
   0.0%
2
   0.3%
CNS cerebrovascular ischemia
2
   0.3%
4
   0.6%
Calcium, serum-high (hypercalcemia)
2
   0.3%
0
   0.0%
Calcium, serum-low (hypocalcemia)
1
   0.2%
8
   1.3%
Carbon monoxide diffusion capacity (DL(co))
3
   0.5%
2
   0.3%
Cardiac General-Other (Specify)
2
   0.3%
3
   0.5%
Cardiac troponin I (cTnI)
0
   0.0%
2
   0.3%
Cardiac-ischemia/infarction
1
   0.2%
1
   0.2%
Cardiopulmonary arrest, cause unknown (non-fatal)
1
   0.2%
2
   0.3%
Cognitive disturbance
1
   0.2%
1
   0.2%
Colitis
0
   0.0%
2
   0.3%
Colitis, infectious (e.g., Clostridium difficile)
0
   0.0%
1
   0.2%
Conduction abnormality - Asystole
1
   0.2%
0
   0.0%
Confusion
1
   0.2%
4
   0.6%
Constipation
4
   0.6%
4
   0.6%
Cough
1
   0.2%
2
   0.3%
Creatinine
0
   0.0%
1
   0.2%
Cytokine release syndrome/acute infusion reaction
0
   0.0%
10
   1.6%
Death - Multi-organ failure
0
   0.0%
2
   0.3%
Death not associated with CTCAE term - Death NOS
1
   0.2%
7
   1.1%
Dehydration
27
   4.3%
31
   4.9%
Dermatology/Skin-Other (Specify)
0
   0.0%
3
   0.5%
Diarrhea
15
   2.4%
19
   3.0%
Dizziness
10
   1.6%
7
   1.1%
Dry eye syndrome
0
   0.0%
1
   0.2%
Dry mouth/salivary gland (xerostomia)
1
   0.2%
0
   0.0%
Dry skin
0
   0.0%
6
   1.0%
Dysphagia (difficulty swallowing)
1
   0.2%
2
   0.3%
Dyspnea (shortness of breath)
21
   3.3%
33
   5.3%
Edema: limb
1
   0.2%
3
   0.5%
Encephalopathy
1
   0.2%
0
   0.0%
Esophagitis
0
   0.0%
2
   0.3%
Extrapyramidal/involuntary movement/restlessness
0
   0.0%
1
   0.2%
Eyelid dysfunction
0
   0.0%
1
   0.2%
Fatigue (asthenia, lethargy, malaise)
74
  11.7%
81
  12.9%
Febrile neutropenia
27
   4.3%
29
   4.6%
Fever in absence of neutropenia, ANC lt1.0x10e9/L
2
   0.3%
0
   0.0%
GGT (gamma-glutamyl transpeptidase)
0
   0.0%
1
   0.2%
Gastritis (including bile reflux gastritis)
0
   0.0%
3
   0.5%
Gastrointestinal-Other (Specify)
1
   0.2%
3
   0.5%
Glucose, serum-high (hyperglycemia)
20
   3.2%
13
   2.1%
Glucose, serum-low (hypoglycemia)
2
   0.3%
2
   0.3%
Heartburn/dyspepsia
0
   0.0%
1
   0.2%
Hemoglobin
60
   9.5%
48
   7.7%
Hemolysis
0
   0.0%
3
   0.5%
Hemorrhage, GI - Abdomen NOS
0
   0.0%
1
   0.2%
Hemorrhage, GI - Duodenum
1
   0.2%
1
   0.2%
Hemorrhage, GI - Esophagus
1
   0.2%
0
   0.0%
Hemorrhage, GI - Jejunum
0
   0.0%
1
   0.2%
Hemorrhage, GI - Lower GI NOS
1
   0.2%
0
   0.0%
Hemorrhage, GI - Upper GI NOS
1
   0.2%
2
   0.3%
Hemorrhage, GI - Varices (esophageal)
1
   0.2%
0
   0.0%
Hemorrhage, GI - Varices (rectal)
1
   0.2%
0
   0.0%
Hemorrhage, pulmo/upper resp- Bronchopulmonary NOS
1
   0.2%
1
   0.2%
Hemorrhage, pulmonary/upper respiratory - Lung
1
   0.2%
3
   0.5%
Hemorrhage, pulmonary/upper respiratory - Nose
2
   0.3%
1
   0.2%
Hemorrhage, pulmonary/upper respiratory - Pleura
1
   0.2%
0
   0.0%
Hemorrhage/Bleeding-Other (Specify)
1
   0.2%
0
   0.0%
Hiccoughs (hiccups, singultus)
1
   0.2%
1
   0.2%
Hot flashes/flushes
1
   0.2%
1
   0.2%
Hypertension
28
   4.4%
17
   2.7%
Hypotension
5
   0.8%
11
   1.8%
Hypoxia
2
   0.3%
6
   1.0%
INR (of prothrombin time)
0
   0.0%
1
   0.2%
Inf (clin/microbio) w/Gr 3-4 neuts - Blood
8
   1.3%
10
   1.6%
Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus
1
   0.2%
0
   0.0%
Inf (clin/microbio) w/Gr 3-4 neuts - Catheter-rel
0
   0.0%
1
   0.2%
Inf (clin/microbio) w/Gr 3-4 neuts - Colon
1
   0.2%
0
   0.0%
Inf (clin/microbio) w/Gr 3-4 neuts - Duodenum
0
   0.0%
1
   0.2%
Inf (clin/microbio) w/Gr 3-4 neuts - Esophagus
0
   0.0%
1
   0.2%
Inf (clin/microbio) w/Gr 3-4 neuts - Lung
9
   1.4%
7
   1.1%
Inf (clin/microbio) w/Gr 3-4 neuts - Oral cav-gums
0
   0.0%
1
   0.2%
Inf (clin/microbio) w/Gr 3-4 neuts - Pleura
1
   0.2%
0
   0.0%
Inf (clin/microbio) w/Gr 3-4 neuts - Skin
1
   0.2%
2
   0.3%
Inf (clin/microbio) w/Gr 3-4 neuts - UTI
1
   0.2%
2
   0.3%
Inf w/normal ANC or Gr 1-2 neutrophils - Bladder
0
   0.0%
1
   0.2%
Inf w/normal ANC or Gr 1-2 neutrophils - Blood
2
   0.3%
4
   0.6%
Inf w/normal ANC or Gr 1-2 neutrophils - Catheter
1
   0.2%
0
   0.0%
Inf w/normal ANC or Gr 1-2 neutrophils - Dental
1
   0.2%
0
   0.0%
Inf w/normal ANC or Gr 1-2 neutrophils - Joint
1
   0.2%
0
   0.0%
Inf w/normal ANC or Gr 1-2 neutrophils - Lung
11
   1.7%
8
   1.3%
Inf w/normal ANC or Gr 1-2 neutrophils - Mucosa
1
   0.2%
0
   0.0%
Inf w/normal ANC or Gr 1-2 neutrophils - Pelvis
0
   0.0%
1
   0.2%
Inf w/normal ANC or Gr 1-2 neutrophils - Perit cav
1
   0.2%
0
   0.0%
Inf w/normal ANC or Gr 1-2 neutrophils - Pleura
0
   0.0%
1
   0.2%
Inf w/normal ANC or Gr 1-2 neutrophils - Skin
0
   0.0%
5
   0.8%
Inf w/normal ANC or Gr 1-2 neutrophils - UTI
1
   0.2%
0
   0.0%
Infection with unknown ANC - Blood
1
   0.2%
1
   0.2%
Infection with unknown ANC - Eye NOS
0
   0.0%
1
   0.2%
Infection with unknown ANC - Lung (pneumonia)
5
   0.8%
3
   0.5%
Infection with unknown ANC - Sinus
2
   0.3%
0
   0.0%
Infection with unknown ANC - Skin (cellulitis)
0
   0.0%
1
   0.2%
Infection with unknown ANC - Upper airway NOS
0
   0.0%
1
   0.2%
Infection with unknown ANC - Urinary tract NOS
2
   0.3%
1
   0.2%
Infection with unknown ANC - Wound
0
   0.0%
1
   0.2%
Infection-Other (Specify)
4
   0.6%
2
   0.3%
Insomnia
1
   0.2%
5
   0.8%
Irregular menses (change from baseline)
0
   0.0%
1
   0.2%
Leukocytes (total WBC)
74
  11.7%
103
  16.4%
Leukoencephalopathy (radiolographic findings)
1
   0.2%
0
   0.0%
Local complication - device/prosthesis-related
0
   0.0%
1
   0.2%
Lymphopenia
39
   6.2%
60
   9.6%
Magnesium, serum-high (hypermagnesemia)
0
   0.0%
1
   0.2%
Magnesium, serum-low (hypomagnesemia)
6
   0.9%
28
   4.5%
Memory impairment
0
   0.0%
1
   0.2%
Mental status
0
   0.0%
1
   0.2%
Metabolic/Laboratory-Other (Specify)
1
   0.2%
0
   0.0%
Mood alteration - anxiety
0
   0.0%
1
   0.2%
Mood alteration - depression
3
   0.5%
2
   0.3%
Mucositis/stomatitis (clinical exam) - Esophagus
1
   0.2%
0
   0.0%
Mucositis/stomatitis (clinical exam) - Oral cavity
2
   0.3%
6
   1.0%
Mucositis/stomatitis (functional/symp) - Oral cav
0
   0.0%
4
   0.6%
Muscle weakness, not d/t neuropathy - Extrem-lower
6
   0.9%
9
   1.4%
Muscle weakness, not d/t neuropathy - Extrem-upper
0
   0.0%
1
   0.2%
Muscle weakness, not d/t neuropathy - Pelvic
0
   0.0%
1
   0.2%
Muscle weakness, not d/t neuropathy - body/general
21
   3.3%
33
   5.3%
Nail changes
0
   0.0%
4
   0.6%
Nasal cavity/paranasal sinus reactions
0
   0.0%
1
   0.2%
Nausea
26
   4.1%
30
   4.8%
Neuroendocrine: ADH secretion abnormality
0
   0.0%
2
   0.3%
Neuropathy: motor
18
   2.8%
10
   1.6%
Neuropathy: sensory
57
   9.0%
36
   5.7%
Neutrophils/granulocytes (ANC/AGC)
158
  25.0%
210
  33.5%
Obstruction, GI - Small bowel NOS
0
   0.0%
1
   0.2%
Obstruction/stenosis of airway - Bronchus
1
   0.2%
0
   0.0%
Ocular/Visual-Other (Specify)
1
   0.2%
1
   0.2%
Opportunistic inf associated w/gt=Gr 2 lymphopenia
1
   0.2%
0
   0.0%
Pain - Abdomen NOS
5
   0.8%
9
   1.4%
Pain - Back
1
   0.2%
2
   0.3%
Pain - Bone
2
   0.3%
1
   0.2%
Pain - Chest wall
1
   0.2%
2
   0.3%
Pain - Chest/thorax NOS
1
   0.2%
2
   0.3%
Pain - Extremity-limb
10
   1.6%
12
   1.9%
Pain - Head/headache
2
   0.3%
1
   0.2%
Pain - Joint
19
   3.0%
19
   3.0%
Pain - Muscle
24
   3.8%
14
   2.2%
Pain - Neck
1
   0.2%
0
   0.0%
Pain - Neuralgia/peripheral nerve
1
   0.2%
1
   0.2%
Pain - Oral cavity
0
   0.0%
1
   0.2%
Pain - Peritoneum
1
   0.2%
0
   0.0%
Pain - Scrotum
1
   0.2%
0
   0.0%
Pain - Skin
0
   0.0%
1
   0.2%
Pain - Stomach
0
   0.0%
1
   0.2%
Pain-Other (Specify)
2
   0.3%
3
   0.5%
Pancreatitis
0
   0.0%
1
   0.2%
Perforation, GI - Colon
1
   0.2%
6
   1.0%
Perforation, GI - Duodenum
1
   0.2%
0
   0.0%
Perforation, GI - Small bowel NOS
0
   0.0%
1
   0.2%
Pericardial effusion (non-malignant)
0
   0.0%
1
   0.2%
Phosphate, serum-low (hypophosphatemia)
2
   0.3%
8
   1.3%
Platelets
51
   8.1%
43
   6.9%
Pleural effusion (non-malignant)
1
   0.2%
0
   0.0%
Pneumonitis/pulmonary infiltrates
2
   0.3%
8
   1.3%
Potassium, serum-high (hyperkalemia)
1
   0.2%
4
   0.6%
Potassium, serum-low (hypokalemia)
22
   3.5%
35
   5.6%
Proteinuria
4
   0.6%
7
   1.1%
Pruritus/itching
0
   0.0%
7
   1.1%
Pulmonary/Upper Respiratory-Other (Specify)
2
   0.3%
2
   0.3%
Rash/desquamation
1
   0.2%
6
   1.0%
Rash: acne/acneiform
0
   0.0%
50
   8.0%
Rash: hand-foot skin reaction
0
   0.0%
4
   0.6%
Renal failure
0
   0.0%
2
   0.3%
Renal/Genitourinary-Other (Specify)
3
   0.5%
0
   0.0%
SVT and nodal arrhythmia - Atrial fibrillation
2
   0.3%
0
   0.0%
SVT and nodal arrhythmia - Atrial flutter
1
   0.2%
1
   0.2%
SVT and nodal arrhythmia - SVT tachycardia
1
   0.2%
1
   0.2%
SVT and nodal arrhythmia - Sinus tachycardia
1
   0.2%
0
   0.0%
Seizure
0
   0.0%
2
   0.3%
Sodium, serum-low (hyponatremia)
29
   4.6%
27
   4.3%
Somnolence/depressed level of consciousness
1
   0.2%
2
   0.3%
Sudden death
0
   0.0%
1
   0.2%
Syncope (fainting)
8
   1.3%
7
   1.1%
Syndromes-Other (Specify)
0
   0.0%
2
   0.3%
Thrombosis/embolism (vascular access-related)
0
   0.0%
4
   0.6%
Thrombosis/thrombus/embolism
26
   4.1%
37
   5.9%
Tinnitus
0
   0.0%
1
   0.2%
Tremor
0
   0.0%
1
   0.2%
Tumor lysis syndrome
0
   0.0%
1
   0.2%
Typhlitis (cecal inflammation)
1
   0.2%
0
   0.0%
Ulcer, GI - Duodenum
1
   0.2%
1
   0.2%
Ulcer, GI - Stomach
0
   0.0%
1
   0.2%
Ulceration
0
   0.0%
1
   0.2%
Uric acid, serum-high (hyperuricemia)
1
   0.2%
0
   0.0%
Urticaria (hives, welts, wheals)
0
   0.0%
4
   0.6%
Ventricular arrhythmia - Ventricular tachycardia
1
   0.2%
0
   0.0%
Ventricular arrhythmia NOS
0
   0.0%
1
   0.2%
Visceral arterial ischemia (non-myocardial)
0
   0.0%
1
   0.2%
Vomiting
19
   3.0%
18
   2.9%
Weight gain
0
   0.0%
1
   0.2%
Weight loss
8
   1.3%
4
   0.6%
Wound complication, non-infectious
0
   0.0%
1
   0.2%
Time Frame Toxicity assessment was evaluated every 3 weeks while on protocol treatment. Chemo and cetuximab is treated for 6 cycles (1 cycle =3 weeks) and Bevacizumab is treated until progression, an average of 6 months.
Adverse Event Reporting Description Limited to eligible patients who started treatment, who did not have a major deviation in the treatment protocol, and whose toxicity profile has been completed.
 
Arm/Group Title Arm I (Chemo +/- Bevacizumab) Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Hide Arm/Group Description

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes with or without bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receiving bevacizumab may continue to receive bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Patients receive paclitaxel and carboplatin with or without bevacizumab as in Arm I. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients may continue to receive cetuximab with or without bevacizumab (as above) in the absence of disease progression or unacceptable toxicity.

Bevacizumab: Given IV

Carboplatin: Given IV

Cetuximab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

All-Cause Mortality
Arm I (Chemo +/- Bevacizumab) Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Affected / at Risk (%) Affected / at Risk (%)
Total   593/657 (90.26%)   570/656 (86.89%) 
Hide Serious Adverse Events
Arm I (Chemo +/- Bevacizumab) Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Affected / at Risk (%) Affected / at Risk (%)
Total   66/632 (10.44%)   97/627 (15.47%) 
Blood and lymphatic system disorders     
DIC (disseminated intravascular coagulation)  1  0/632 (0.00%)  1/627 (0.16%) 
Febrile neutropenia  1  5/632 (0.79%)  3/627 (0.48%) 
Hemoglobin  1  2/632 (0.32%)  1/627 (0.16%) 
Thrombotic microangiopathy  1  0/632 (0.00%)  1/627 (0.16%) 
Cardiac disorders     
Cardiac General-Other  1  3/632 (0.47%)  3/627 (0.48%) 
Cardiac-ischemia/infarction  1  2/632 (0.32%)  1/627 (0.16%) 
Cardiopulmonary arrest, cause unknown (non-fatal)  1  1/632 (0.16%)  2/627 (0.32%) 
SVT and nodal arrhythmia - Atrial fibrillation  1  2/632 (0.32%)  0/627 (0.00%) 
Ventricular arrhythmia NOS  1  0/632 (0.00%)  1/627 (0.16%) 
Endocrine disorders     
Adrenal insufficiency  1  0/632 (0.00%)  1/627 (0.16%) 
Gastrointestinal disorders     
Colitis  1  1/632 (0.16%)  0/627 (0.00%) 
Constipation  1  0/632 (0.00%)  1/627 (0.16%) 
Diarrhea  1  0/632 (0.00%)  1/627 (0.16%) 
Gastrointestinal-Other  1  1/632 (0.16%)  2/627 (0.32%) 
Hemorrhage, GI - Duodenum  1  1/632 (0.16%)  0/627 (0.00%) 
Hemorrhage, GI - Esophagus  1  1/632 (0.16%)  0/627 (0.00%) 
Hemorrhage, GI - Upper GI NOS  1  0/632 (0.00%)  1/627 (0.16%) 
Perforation, GI - Colon  1  0/632 (0.00%)  4/627 (0.64%) 
Perforation, GI - Duodenum  1  1/632 (0.16%)  0/627 (0.00%) 
Perforation, GI - Stomach  1  1/632 (0.16%)  0/627 (0.00%) 
Ulcer, GI - Duodenum  1  1/632 (0.16%)  0/627 (0.00%) 
General disorders     
Death - Multi-organ failure  1  0/632 (0.00%)  2/627 (0.32%) 
Death not associated with CTCAE term - Death NOS  1  12/632 (1.90%)  12/627 (1.91%) 
Sudden death  1  0/632 (0.00%)  1/627 (0.16%) 
Syndromes-Other  1  1/632 (0.16%)  1/627 (0.16%) 
Hepatobiliary disorders     
Liver dysfunction/failure (clinical)  1  0/632 (0.00%)  1/627 (0.16%) 
Immune system disorders     
Allergic reaction/hypersensitivity  1  0/632 (0.00%)  8/627 (1.28%) 
Cytokine release syndrome/acute infusion reaction  1  0/632 (0.00%)  3/627 (0.48%) 
Infections and infestations     
Inf (clin/microbio) w/Gr 3-4 neuts - Blood  1  0/632 (0.00%)  5/627 (0.80%) 
Inf (clin/microbio) w/Gr 3-4 neuts - Esophagus  1  0/632 (0.00%)  1/627 (0.16%) 
Inf (clin/microbio) w/Gr 3-4 neuts - Lung  1  1/632 (0.16%)  0/627 (0.00%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Blood  1  1/632 (0.16%)  1/627 (0.16%) 
Inf w/normal ANC or Gr 1-2 neutrophils - Lung  1  0/632 (0.00%)  2/627 (0.32%) 
Infection with unknown ANC - Blood  1  2/632 (0.32%)  1/627 (0.16%) 
Injury, poisoning and procedural complications     
Intra-operative Injury-Other  1  1/632 (0.16%)  0/627 (0.00%) 
Vessel injury-artery - Aorta  1  1/632 (0.16%)  0/627 (0.00%) 
Investigations     
ALT, SGPT (serum glutamic pyruvic transaminase)  1  0/632 (0.00%)  1/627 (0.16%) 
AST, SGOT  1  0/632 (0.00%)  1/627 (0.16%) 
Carbon monoxide diffusion capacity (DL(co))  1  8/632 (1.27%)  8/627 (1.28%) 
Creatinine  1  1/632 (0.16%)  0/627 (0.00%) 
Leukocytes (total WBC)  1  0/632 (0.00%)  1/627 (0.16%) 
Lymphopenia  1  0/632 (0.00%)  1/627 (0.16%) 
Neuroendocrine: ADH secretion abnormality  1  0/632 (0.00%)  1/627 (0.16%) 
Neutrophils/granulocytes (ANC/AGC)  1  1/632 (0.16%)  1/627 (0.16%) 
Platelets  1  0/632 (0.00%)  3/627 (0.48%) 
Metabolism and nutrition disorders     
Acidosis (metabolic or respiratory)  1  1/632 (0.16%)  0/627 (0.00%) 
Anorexia  1  0/632 (0.00%)  1/627 (0.16%) 
Dehydration  1  1/632 (0.16%)  1/627 (0.16%) 
Magnesium, serum-low (hypomagnesemia)  1  0/632 (0.00%)  1/627 (0.16%) 
Potassium, serum-high (hyperkalemia)  1  0/632 (0.00%)  2/627 (0.32%) 
Potassium, serum-low (hypokalemia)  1  1/632 (0.16%)  1/627 (0.16%) 
Sodium, serum-low (hyponatremia)  1  2/632 (0.32%)  3/627 (0.48%) 
Uric acid, serum-high (hyperuricemia)  1  1/632 (0.16%)  0/627 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscle weakness, not d/t neuropathy - body/general  1  1/632 (0.16%)  0/627 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Death - Disease progression NOS  1  9/632 (1.42%)  17/627 (2.71%) 
Tumor flare  1  1/632 (0.16%)  0/627 (0.00%) 
Nervous system disorders     
CNS cerebrovascular ischemia  1  1/632 (0.16%)  3/627 (0.48%) 
Neurology-Other  1  0/632 (0.00%)  1/627 (0.16%) 
Renal and urinary disorders     
Renal failure  1  1/632 (0.16%)  0/627 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Aspiration  1  0/632 (0.00%)  2/627 (0.32%) 
Carbon monoxide diffusion capacity (DL(co))  1  8/632 (1.27%)  8/627 (1.28%) 
Dyspnea (shortness of breath)  1  6/632 (0.95%)  5/627 (0.80%) 
Hemorrhage, pulmo/upper resp- Bronchopulmonary NOS  1  1/632 (0.16%)  2/627 (0.32%) 
Hemorrhage, pulmonary/upper respiratory - Lung  1  0/632 (0.00%)  1/627 (0.16%) 
Hemorrhage, pulmonary/upper respiratory - Pleura  1  1/632 (0.16%)  0/627 (0.00%) 
Hypoxia  1  2/632 (0.32%)  2/627 (0.32%) 
Obstruction/stenosis of airway - Bronchus  1  1/632 (0.16%)  0/627 (0.00%) 
Pleural effusion (non-malignant)  1  0/632 (0.00%)  3/627 (0.48%) 
Pneumonitis/pulmonary infiltrates  1  1/632 (0.16%)  2/627 (0.32%) 
Pulmonary/Upper Respiratory-Other  1  2/632 (0.32%)  2/627 (0.32%) 
Voice changes/dysarthria  1  0/632 (0.00%)  1/627 (0.16%) 
Vascular disorders     
Hypertension  1  1/632 (0.16%)  0/627 (0.00%) 
Hypotension  1  0/632 (0.00%)  4/627 (0.64%) 
Thrombosis/thrombus/embolism  1  4/632 (0.63%)  4/627 (0.64%) 
Visceral arterial ischemia (non-myocardial)  1  0/632 (0.00%)  1/627 (0.16%) 
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm I (Chemo +/- Bevacizumab) Arm II (Chemo, Cetuximab, +/- Bevacizumab)
Affected / at Risk (%) Affected / at Risk (%)
Total   619/632 (97.94%)   611/627 (97.45%) 
Blood and lymphatic system disorders     
Hemoglobin  1  434/632 (68.67%)  384/627 (61.24%) 
Eye disorders     
Vision-blurred vision  1  38/632 (6.01%)  33/627 (5.26%) 
Gastrointestinal disorders     
Constipation  1  261/632 (41.30%)  302/627 (48.17%) 
Diarrhea  1  195/632 (30.85%)  243/627 (38.76%) 
Heartburn/dyspepsia  1  70/632 (11.08%)  109/627 (17.38%) 
Mucositis/stomatitis (clinical exam) - Oral cavity  1  74/632 (11.71%)  162/627 (25.84%) 
Mucositis/stomatitis (functional/symp) - Oral cav  1  36/632 (5.70%)  74/627 (11.80%) 
Nausea  1  304/632 (48.10%)  318/627 (50.72%) 
Pain - Abdomen NOS  1  60/632 (9.49%)  86/627 (13.72%) 
Vomiting  1  150/632 (23.73%)  168/627 (26.79%) 
General disorders     
Edema: limb  1  80/632 (12.66%)  84/627 (13.40%) 
Fatigue (asthenia, lethargy, malaise)  1  494/632 (78.16%)  474/627 (75.60%) 
Fever in absence of neutropenia, ANC lt1.0x10e9/L  1  56/632 (8.86%)  47/627 (7.50%) 
Pain - Chest/thorax NOS  1  72/632 (11.39%)  72/627 (11.48%) 
Pain-Other  1  63/632 (9.97%)  80/627 (12.76%) 
Rigors/chills  1  49/632 (7.75%)  56/627 (8.93%) 
Immune system disorders     
Allergic reaction/hypersensitivity  1  37/632 (5.85%)  90/627 (14.35%) 
Infections and infestations     
Infection-Other  1  35/632 (5.54%)  53/627 (8.45%) 
Investigations     
ALT, SGPT (serum glutamic pyruvic transaminase)  1  82/632 (12.97%)  148/627 (23.60%) 
AST, SGOT  1  81/632 (12.82%)  141/627 (22.49%) 
Alkaline phosphatase  1  138/632 (21.84%)  169/627 (26.95%) 
Bilirubin (hyperbilirubinemia)  1  30/632 (4.75%)  32/627 (5.10%) 
Creatinine  1  52/632 (8.23%)  45/627 (7.18%) 
Leukocytes (total WBC)  1  258/632 (40.82%)  289/627 (46.09%) 
Lymphopenia  1  139/632 (21.99%)  166/627 (26.48%) 
Metabolic/Laboratory-Other  1  39/632 (6.17%)  49/627 (7.81%) 
Neutrophils/granulocytes (ANC/AGC)  1  252/632 (39.87%)  305/627 (48.64%) 
Platelets  1  270/632 (42.72%)  233/627 (37.16%) 
Weight loss  1  163/632 (25.79%)  181/627 (28.87%) 
Metabolism and nutrition disorders     
Albumin, serum-low (hypoalbuminemia)  1  211/632 (33.39%)  244/627 (38.92%) 
Anorexia  1  245/632 (38.77%)  241/627 (38.44%) 
Calcium, serum-low (hypocalcemia)  1  117/632 (18.51%)  179/627 (28.55%) 
Dehydration  1  104/632 (16.46%)  118/627 (18.82%) 
Glucose, serum-high (hyperglycemia)  1  290/632 (45.89%)  266/627 (42.42%) 
Magnesium, serum-low (hypomagnesemia)  1  201/632 (31.80%)  349/627 (55.66%) 
Potassium, serum-high (hyperkalemia)  1  34/632 (5.38%)  34/627 (5.42%) 
Potassium, serum-low (hypokalemia)  1  135/632 (21.36%)  200/627 (31.90%) 
Sodium, serum-low (hyponatremia)  1  194/632 (30.70%)  205/627 (32.70%) 
Musculoskeletal and connective tissue disorders     
Muscle weakness, not d/t neuropathy - Extrem-lower  1  56/632 (8.86%)  59/627 (9.41%) 
Muscle weakness, not d/t neuropathy - body/general  1  110/632 (17.41%)  122/627 (19.46%) 
Pain - Back  1  109/632 (17.25%)  126/627 (20.10%) 
Pain - Bone  1  50/632 (7.91%)  60/627 (9.57%) 
Pain - Chest wall  1  43/632 (6.80%)  38/627 (6.06%) 
Pain - Extremity-limb  1  131/632 (20.73%)  150/627 (23.92%) 
Pain - Joint  1  192/632 (30.38%)  194/627 (30.94%) 
Pain - Muscle  1  160/632 (25.32%)  149/627 (23.76%) 
Nervous system disorders     
Dizziness  1  129/632 (20.41%)  167/627 (26.63%) 
Neuropathy: motor  1  62/632 (9.81%)  67/627 (10.69%) 
Neuropathy: sensory  1  386/632 (61.08%)  368/627 (58.69%) 
Pain - Head/headache  1  80/632 (12.66%)  84/627 (13.40%) 
Taste alteration (dysgeusia)  1  131/632 (20.73%)  147/627 (23.44%) 
Psychiatric disorders     
Confusion  1  31/632 (4.91%)  40/627 (6.38%) 
Insomnia  1  95/632 (15.03%)  131/627 (20.89%) 
Mood alteration - anxiety  1  61/632 (9.65%)  70/627 (11.16%) 
Mood alteration - depression  1  58/632 (9.18%)  60/627 (9.57%) 
Renal and urinary disorders     
Proteinuria  1  36/632 (5.70%)  50/627 (7.97%) 
Respiratory, thoracic and mediastinal disorders     
Allergic rhinitis  1  48/632 (7.59%)  66/627 (10.53%) 
Cough  1  239/632 (37.82%)  248/627 (39.55%) 
Dyspnea (shortness of breath)  1  285/632 (45.09%)  290/627 (46.25%) 
Hemorrhage, pulmonary/upper respiratory - Nose  1  86/632 (13.61%)  115/627 (18.34%) 
Pulmonary/Upper Respiratory-Other  1  23/632 (3.64%)  38/627 (6.06%) 
Voice changes/dysarthria  1  40/632 (6.33%)  37/627 (5.90%) 
Skin and subcutaneous tissue disorders     
Dermatology/Skin-Other  1  17/632 (2.69%)  82/627 (13.08%) 
Dry skin  1  64/632 (10.13%)  220/627 (35.09%) 
Hair loss/Alopecia (scalp or body)  1  315/632 (49.84%)  293/627 (46.73%) 
Nail changes  1  37/632 (5.85%)  67/627 (10.69%) 
Pruritus/itching  1  49/632 (7.75%)  122/627 (19.46%) 
Rash/desquamation  1  42/632 (6.65%)  155/627 (24.72%) 
Rash: acne/acneiform  1  40/632 (6.33%)  425/627 (67.78%) 
Rash: hand-foot skin reaction  1  4/632 (0.63%)  54/627 (8.61%) 
Vascular disorders     
Hypertension  1  124/632 (19.62%)  96/627 (15.31%) 
Hypotension  1  55/632 (8.70%)  79/627 (12.60%) 
Thrombosis/thrombus/embolism  1  54/632 (8.54%)  68/627 (10.85%) 
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Lung Committee Statistican
Organization: SWOG Statistics & Data Management Center
Phone: 2066675712
EMail: jmiao@fredhutch.org
Layout table for additonal information
Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00946712    
Other Study ID Numbers: S0819
NCI-2009-01664 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000649817
S0819 ( Other Identifier: SWOG )
S0819 ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
U10CA032102 ( U.S. NIH Grant/Contract )
First Submitted: July 24, 2009
First Posted: July 27, 2009
Results First Submitted: December 6, 2018
Results First Posted: March 7, 2019
Last Update Posted: May 19, 2021