Cetuximab + / - Carboplatin for Estrogen Receptor-Negative, Progesterone Receptor-Negative Metastatic Breast Cancer

• Sponsor: UNC Lineberger Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00232505
• Collaborator: National Cancer Institute (NCI) (NIH), Bristol-Myers Squibb (Industry), Avon Foundation (Other), National Center for Research Resources (NCRR) (NIH)
• Enrollment: 112
• Locations: 14
• Arms: 2
• Actual Duration (Months): 81.3
• Patients Per Site: 8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving cetuximab together with carboplatin is more effective than giving cetuximab alone in treating metastatic breast cancer.

PURPOSE: This randomized phase II trial is studying cetuximab and carboplatin to see how well they work compared with cetuximab alone in treating women with estrogen receptor-negative (ER-), progesterone receptor-negative (PR-) metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: cetuximab; Drug: carboplatin	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Compare the overall response rate in women with estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor 2 (HER2)-nonoverexpressing metastatic breast cancer treated with cetuximab with vs without carboplatin.

Secondary

• Compare the time to disease progression in patients treated with these regimens.

• Correlate downstream effects of epidermal growth factor receptor (EGFR) inhibitor on Mitogen-activated protein kinases (MAPK), Protein kinase B (AKT), monoclonal antibody Ki-67 (Ki67), and EGFR-dependent signaling, proliferation, and apoptosis with toxicity and response in patients with accessible tumors treated with these regimens.

• Determine the changes in biomarkers and gene expression in circulating tumor cells during treatment.

• Compare the overall survival rate in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cetuximab IV over 60-120 minutes once a week.

• Arm II: Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15.

In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment in arm I may cross over to arm II.

Blood samples are collected periodically throughout study for correlative biomarker analysis by Immunohistochemistry (IHC) and gene expression analysis.

After completion of study treatment, patients are followed every 4 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Cetuximab Alone and in Combination With Carboplatin in ER-Negative, PR-Negative, HER-2 Nonoverexpressing Metastatic Breast Cancer
• Actual Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Jun 21, 2010
• Actual Study Completion Date: Aug 12, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cetuximab Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II.	Biological: cetuximab; Given IV; Other Names: Erbitux
Experimental: Cetuximab and Carboplatin Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Biological: cetuximab; Given IV; Other Names: Erbitux ; Drug: carboplatin; Given IV; Other Names: Paraplatin

Outcome Measures

Primary Outcome Measures

1. Overall Disease Response Rate [5 years]

   Overall response rate of single agent cetuximab and cetuximab + carboplatin will be measured by radiographic response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria every 8 weeks until subject experiences disease progression. Overall response will be measured as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD).Per RECIST v1.0 for target lesions and assessed by CT (spiral): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, 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; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression

Secondary Outcome Measures

1. Overall Survival [Every four months until death of any cause or end of data collection up to 40 months]

   Subjects will be contacted every 4 months after discontinuation of active treatment to assess survival.

2. Progression-Free Survival [Every four months until progression, death of any cause, or end of data collection up to 40 months]

   Time to disease progression of cetuximab or cetuximab + carboplatin as indicated by radiographic assessment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

• Metastatic (stage IV) disease

• Measurable disease by RECIST criteria

• Irradiated lesions are not considered measurable disease

• Central nervous system (CNS) metastases allowed if disease is stable (no evidence of progression) ≥ 3 months after local therapy

• No lesions identifiable only by positron emission tomography (PET) scan

• HER2 nonoverexpressing disease by IHC (0 or 1) or non-gene amplified by Fluorescence In Situ Hybridization (FISH)

• HER2 2+ by IHC allowed

• Hormone receptor status:

• Estrogen receptor-negative and progesterone receptor-negative tumor

Inclusion Criteria

• At least 18 years of age

• Metastatic breast cancer (Stage IV) with measurable disease by RECIST criteria

• No more than three prior chemotherapy regimens either in the adjuvant or metastatic setting.

• Histologically documented (either primary or metastatic site) breast cancer that is estrogen receptor- (ER-) negative, PR-negative, and HER-2 nonoverexpressing by immunohistochemistry (0,1) or non-gene amplified by FISH performed upon the primary tumor or metastatic lesion. HER-2 2+ by immunohistochemistry is usually negative by FISH, and this confirmatory test should be performed when possible, however may participate if fulfill other criteria.

• Completion of prior chemotherapy at least 3 weeks prior to study entry.

• Patients may have received therapy (ies) in the adjuvant or metastatic setting, however must have discontinued prior to entry. Patients may receive concurrent bisphosphonates, however if taking bisphosphonates, bone lesions may not be used for progression or response.

• Radiation therapy must be completed at least 2 weeks prior to study entry, and radiated lesions may not serve as measurable disease.

• Patients may have CNS metastases if stable (no evidence of progression) > 3 months after local therapy.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and life expectancy of at least 6 months.

• Adequate organ function defined as:absolute neutrophil count (ANC) > 1500/mm3, plts > 100,000/mm3, creatinine clearance >50 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN) (or ≤5 x ULN in case of liver metastases); total bilirubin ≤1.5 mg/dL.

• Tissue block available for EGFR studies is recommended, although will not exclude patients from participating.

• Pregnant or lactating women will be excluded. Women of child bearing potential must have documented negative pregnancy test within two weeks of study entry and agree to acceptable birth control during the duration of the study therapy.

• Signed written informed consent.

Exclusion Criteria

• Lesions identifiable only by PET.

• More than three prior chemotherapy regimens (including adjuvant). Sequential regimens such as doxorubicin and cyclophosphamide followed by paclitaxel (AC-paclitaxel) are considered one regimen.

• Prior therapy which specifically and directly targets the EGFR pathway with therapeutic intent.

• Prior platinum agent for metastatic disease. If platinum agent was used adjuvantly, the patient must have had at least 12 months disease-free interval prior to relapse.

• Prior severe infusion reaction to a monoclonal antibody.

• Major medical conditions that might affect study participation (uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection).

• Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy that is either symptomatic or asymptomatic but with decreased ejection fraction <45%

• Other significant comorbid condition which the investigator feels might compromise effective and safe participation in the study.

• Inability to comply with the requirements of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama	United States	35294
2	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
3	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington, D.C.	District of Columbia	United States	20007
4	Washington Cancer Institute at Washington Hospital Center	Washington, D.C.	District of Columbia	United States	20010
5	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
6	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
7	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
8	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
9	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
10	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
11	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
12	Rex Cancer Center at Rex Hospital	Raleigh	North Carolina	United States	27607
13	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
14	Baylor University Medical Center - Houston	Houston	Texas	United States	77030

Sponsors and Collaborators

• UNC Lineberger Comprehensive Cancer Center
• National Cancer Institute (NCI)
• Bristol-Myers Squibb
• Avon Foundation
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Lisa A. Carey, MD, UNC Lineberger Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of North Carolina Lineberger Comprehensive Cancer Center

Publications

None provided.

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00232505
• Other Study ID Numbers: LCCC 0403; M01RR000046; CA058223; NCT00420329; NCT00492375
• First Posted: Oct 4, 2005
• Last Update Posted: Jun 28, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by UNC Lineberger Comprehensive Cancer Center: recurrent breast cancer; stage IV breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Carboplatin; Cetuximab

Study Results

Participant Flow

Recruitment Details	Subjects were recruited between December 2005 and October 2007 from thirteen cancer centers throughout the US.
Pre-assignment Detail	Four patients declined participation for personal reasons, three were screen failures, three had death or progression during the screening period.

Arm/Group Title	Cetuximab	Cetuximab and Carboplatin
Arm/Group Description	Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV	Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV
Period Title: Overall Study
STARTED	31	71
Not Evaluable	0	6
Early Progressors	2	5
Off Protocol	5	0
COMPLETED	26	60
NOT COMPLETED	5	11

Baseline Characteristics

Arm/Group Title	Cetuximab	Cetuximab and Carboplatin	Total
Arm/Group Description	Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV	Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV	Total of all reporting groups
Overall Participants	31	71	102
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	49	52	50.5
Sex: Female, Male (Count of Participants)
Female	31 100%	71 100%	102 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.2%	1 1.4%	2 2%
Asian	0 0%	2 2.8%	2 2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	11 35.5%	17 23.9%	28 27.5%
White	19 61.3%	51 71.8%	70 68.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	31 100%	71 100%	102 100%
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
0	17 54.8%	37 52.1%	54 52.9%
1	14 45.2%	28 39.4%	42 41.2%
2	0 0%	4 5.6%	4 3.9%
missing	0 0%	2 2.8%	2 2%
Menopausal Status (Count of Participants)
Postmenopausal	21 67.7%	56 78.9%	77 75.5%
Pre- or perimenopausal	10 32.3%	15 21.1%	25 24.5%
Dominant metastatic site (Count of Participants)
Lung	9 29%	20 28.2%	29 28.4%
Liver	8 25.8%	17 23.9%	25 24.5%
Lymph nodes	4 12.9%	14 19.7%	18 17.6%
Locoregional	5 16.1%	10 14.1%	15 14.7%
Bone	1 3.2%	4 5.6%	5 4.9%
Skin/soft tissue	3 9.7%	5 7%	8 7.8%
Other	1 3.2%	1 1.4%	2 2%
Treatment (participants) [Number]
Prior chemotherapy	30 96.8%	67 94.4%	97 95.1%
Adjuvant/neoadjuvant	26 83.9%	60 84.5%	86 84.3%
Metastatic	21 67.7%	34 47.9%	55 53.9%

Outcome Measures

1. Primary Outcome

Title	Overall Disease Response Rate
Description	Overall response rate of single agent cetuximab and cetuximab + carboplatin will be measured by radiographic response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria every 8 weeks until subject experiences disease progression. Overall response will be measured as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD).Per RECIST v1.0 for target lesions and assessed by CT (spiral): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, 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; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cetuximab	Cetuximab and Carboplatin After Cetuximab Alone	Cetuximab and Carboplatin	Cetuximab and Carboplatin Subset
Arm/Group Description	Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV	Patients from Arm 1 who progressed on cetuximab alone who went on to receive cetuximab + carboplatin	Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV	patients receiving cetuximab and carboplatin who had confirmed basal-like disease by quantitative realtime polymerase chain reaction-based intrinsic subtype assay
Measure Participants	31	25	71	51
Complete response	0 0%	0 0%	1 1%	1 NaN
Partial response	2 6.5%	4 5.6%	11 10.8%	17 NaN
Stable disease	3 9.7%	7 9.9%	15 14.7%	8 NaN
Stable disease > 6 months	1 3.2%	3 4.2%	10 9.8%	7 NaN
Progressive disease	26 83.9%	12 16.9%	38 37.3%	32 NaN
Not evaluable	0 0%	2 2.8%	6 5.9%	3 NaN

2. Secondary Outcome

Title	Overall Survival
Description	Subjects will be contacted every 4 months after discontinuation of active treatment to assess survival.
Time Frame	Every four months until death of any cause or end of data collection up to 40 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cetuximab	Cetuximab and Carboplatin
Arm/Group Description	Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV	Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV
Measure Participants	31	71
Baseline	31 100%	71 100%
4 months	22 71%	56 78.9%
8 months	12 38.7%	41 57.7%
12 months	9 29%	30 42.3%
16 months	8 25.8%	23 32.4%
20 months	8 25.8%	19 26.8%
24 months	6 19.4%	8 11.3%
28 months	5 16.1%	4 5.6%
32 months	1 3.2%	3 4.2%
36 months	1 3.2%	2 2.8%
40 months	0 0%	0 0%

3. Secondary Outcome

Title	Progression-Free Survival
Description	Time to disease progression of cetuximab or cetuximab + carboplatin as indicated by radiographic assessment
Time Frame	Every four months until progression, death of any cause, or end of data collection up to 40 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cetuximab	Cetuximab and Carboplatin
Arm/Group Description	Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV	Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV
Measure Participants	31	71
Baseline	31 100%	71 100%
4 months	4 12.9%	27 38%
8 months	2 6.5%	11 15.5%
12 months	2 6.5%	7 9.9%
16 months	1 3.2%	7 9.9%
20 months	1 3.2%	6 8.5%
24 months	1 3.2%	6 8.5%
28 months	1 3.2%	1 1.4%
32 months	1 3.2%	1 1.4%
36 months	1 3.2%	1 1.4%
40 months	0 0%	0 0%

Adverse Events

Time Frame	Adverse events were collected up to 30 days after treatment
Adverse Event Reporting Description	Categorical "Other, Specify" events listed below include verbatim from data collection source in footnotes
Arm/Group Title	Cetuximab		Cetuximab and Carboplatin After Cetuximab Alone		Cetuximab and Carboplatin
Arm/Group Description	Patients receive cetuximab IV over 60-120 minutes once a week. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment may cross over to arm II. cetuximab: Given IV		Patients from Arm 1 who progressed on cetuximab alone who went on to receive cetuximab + carboplatin		Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV carboplatin: Given IV
All Cause Mortality
	Cetuximab		Cetuximab and Carboplatin After Cetuximab Alone		Cetuximab and Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cetuximab		Cetuximab and Carboplatin After Cetuximab Alone		Cetuximab and Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/31 (9.7%)		8/25 (32%)		20/71 (28.2%)
Blood and lymphatic system disorders
Edema: limb	2/31 (6.5%)		1/25 (4%)		0/71 (0%)
Neutrophils/granulocytes (ANC/AGC)	0/31 (0%)		0/25 (0%)		1/71 (1.4%)
Cardiac disorders
Cardiac General - Other (Specify, __)	0/31 (0%)		1/25 (4%)		0/71 (0%)
Cardiac General - Other (Specify, __)	0/31 (0%)		0/25 (0%)		1/71 (1.4%)
Left ventricular diastolic dysfunction	0/31 (0%)		1/25 (4%)		0/71 (0%)
Supraventricular and nodal arrhythmia - Atrial tachycardia/Paroxysmal Atrial Tachycardia	0/31 (0%)		0/25 (0%)		1/71 (1.4%)
Supraventricular and nodal arrhythmia - Sinus tachycardia	0/31 (0%)		1/25 (4%)		0/71 (0%)
Ear and labyrinth disorders
Pain - Middle ear	0/31 (0%)		1/25 (4%)		0/71 (0%)
Gastrointestinal disorders
Diarrhea	0/31 (0%)		0/25 (0%)		1/71 (1.4%)
Gastrointestinal - Other (Specify, __)	1/31 (3.2%)		0/25 (0%)		0/71 (0%)
Gastrointestinal - Other (Specify, __)	0/31 (0%)		1/25 (4%)		0/71 (0%)
Hemorrhage, GI - Esophagus	0/31 (0%)		1/25 (4%)		0/71 (0%)
Nausea	1/31 (3.2%)		0/25 (0%)		2/71 (2.8%)
Pain - Abdomen NOS	0/31 (0%)		1/25 (4%)		1/71 (1.4%)
Vomiting	0/31 (0%)		1/25 (4%)		3/71 (4.2%)
General disorders
Extremity-lower (gait/walking)	0/31 (0%)		0/25 (0%)		1/71 (1.4%)
Fatigue (asthenia, lethargy, malaise)	1/31 (3.2%)		1/25 (4%)		1/71 (1.4%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	0/31 (0%)		1/25 (4%)		0/71 (0%)
Pain - Chest/thorax NOS	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Pain - Other (Specify, __)	0/31 (0%)		1/25 (4%)		0/71 (0%)
Pain - Other (Specify, __)	0/31 (0%)		2/25 (8%)		0/71 (0%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	0/31 (0%)		3/25 (12%)		0/71 (0%)
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e	0/31 (0%)		1/25 (4%)		0/71 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Skin (cellulitis)	0/31 (0%)		1/25 (4%)		0/71 (0%)
Injury, poisoning and procedural complications
Thrombosis/embolism (vascular access-related)	0/31 (0%)		0/25 (0%)		1/71 (1.4%)
Metabolism and nutrition disorders
Anorexia	0/31 (0%)		2/25 (8%)		1/71 (1.4%)
Dehydration	0/31 (0%)		1/25 (4%)		2/71 (2.8%)
Magnesium, serum-low (hypomagnesemia)	0/31 (0%)		0/25 (0%)		1/71 (1.4%)
Potassium, serum-low (hypokalemia)	0/31 (0%)		0/25 (0%)		3/71 (4.2%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy) - Right-sided	0/31 (0%)		1/25 (4%)		0/71 (0%)
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	2/31 (6.5%)		0/25 (0%)		0/71 (0%)
Pain - Bone	1/31 (3.2%)		0/25 (0%)		0/71 (0%)
Pain - Chest wall	0/31 (0%)		1/25 (4%)		0/71 (0%)
Pain - Extremity-limb	1/31 (3.2%)		0/25 (0%)		0/71 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain - Tumor pain	0/31 (0%)		0/25 (0%)		1/71 (1.4%)
Secondary Malignancy - possibly related to cancer treatment (Specify, __)	0/31 (0%)		1/25 (4%)		0/71 (0%)
Nervous system disorders
Hemorrhage, CNS	0/31 (0%)		0/25 (0%)		1/71 (1.4%)
Seizure	0/31 (0%)		2/25 (8%)		0/71 (0%)
Somnolence/depressed level of consciousness	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Psychiatric disorders
Confusion	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Respiratory, thoracic and mediastinal disorders
Cough	0/31 (0%)		1/25 (4%)		0/71 (0%)
Dyspnea (shortness of breath)	0/31 (0%)		2/25 (8%)		7/71 (9.9%)
Hypoxia	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Pleural effusion (non-malignant)	0/31 (0%)		0/25 (0%)		1/71 (1.4%)
Pneumonitis/pulmonary infiltrates	0/31 (0%)		1/25 (4%)		0/71 (0%)
Pulmonary/Upper Respiratory - Other (Specify, __)	0/31 (0%)		1/25 (4%)		0/71 (0%)
Skin and subcutaneous tissue disorders
Ulceration	0/31 (0%)		1/25 (4%)		0/71 (0%)
Vascular disorders
Flushing	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Hypotension	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Thrombosis/thrombus/embolism	0/31 (0%)		1/25 (4%)		4/71 (5.6%)
Other (Not Including Serious) Adverse Events
	Cetuximab		Cetuximab and Carboplatin After Cetuximab Alone		Cetuximab and Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/31 (87.1%)		24/25 (96%)		68/71 (95.8%)
Blood and lymphatic system disorders
Edema: limb	5/31 (16.1%)		1/25 (4%)		9/71 (12.7%)
Hemoglobin	2/31 (6.5%)		2/25 (8%)		13/71 (18.3%)
Leukocytes (total WBC)	0/31 (0%)		1/25 (4%)		9/71 (12.7%)
Lymphopenia	1/31 (3.2%)		0/25 (0%)		5/71 (7%)
Neutrophils/granulocytes (ANC/AGC)	1/31 (3.2%)		5/25 (20%)		16/71 (22.5%)
Pain - Lymph node	0/31 (0%)		0/25 (0%)		3/71 (4.2%)
Platelets	0/31 (0%)		2/25 (8%)		14/71 (19.7%)
Cardiac disorders
Cardiac General - Other (Specify, __)	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Hypertension	1/31 (3.2%)		0/25 (0%)		2/71 (2.8%)
Pain - Cardiac/heart	0/31 (0%)		1/25 (4%)		2/71 (2.8%)
Eye disorders
Dry eye syndrome	1/31 (3.2%)		0/25 (0%)		2/71 (2.8%)
Ocular/Visual - Other (Specify, __)	0/31 (0%)		0/25 (0%)		4/71 (5.6%)
Vision-blurred vision	1/31 (3.2%)		1/25 (4%)		0/71 (0%)
Vision-flashing lights/floaters	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Watery eye (epiphora, tearing)	2/31 (6.5%)		0/25 (0%)		1/71 (1.4%)
Gastrointestinal disorders
Constipation	3/31 (9.7%)		4/25 (16%)		28/71 (39.4%)
Diarrhea	6/31 (19.4%)		1/25 (4%)		18/71 (25.4%)
Dry mouth/salivary gland (xerostomia)	0/31 (0%)		1/25 (4%)		1/71 (1.4%)
Dysphagia (difficulty swallowing)	0/31 (0%)		1/25 (4%)		1/71 (1.4%)
Gastritis (including bile reflux gastritis)	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Gastrointestinal - Other (Specify, __)	3/31 (9.7%)		1/25 (4%)		3/71 (4.2%)
Heartburn/dyspepsia	3/31 (9.7%)		1/25 (4%)		8/71 (11.3%)
Mucositis/stomatitis (clinical exam) - Oral cavity	2/31 (6.5%)		2/25 (8%)		14/71 (19.7%)
Mucositis/stomatitis (functional/symptomatic) - Oral cavity	5/31 (16.1%)		1/25 (4%)		5/71 (7%)
Nausea	7/31 (22.6%)		10/25 (40%)		35/71 (49.3%)
Pain - Abdomen NOS	3/31 (9.7%)		3/25 (12%)		4/71 (5.6%)
Vomiting	4/31 (12.9%)		4/25 (16%)		21/71 (29.6%)
General disorders
Constitutional Symptoms - Other (Specify, __)	0/31 (0%)		0/25 (0%)		6/71 (8.5%)
Extremity-lower (gait/walking)	2/31 (6.5%)		0/25 (0%)		0/71 (0%)
Fatigue (asthenia, lethargy, malaise)	14/31 (45.2%)		14/25 (56%)		45/71 (63.4%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	3/31 (9.7%)		2/25 (8%)		3/71 (4.2%)
Pain - Other (Specify, __)	8/31 (25.8%)		4/25 (16%)		10/71 (14.1%)
Pain - Pain NOS	1/31 (3.2%)		0/25 (0%)		3/71 (4.2%)
Rigors/chills	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Hepatobiliary disorders
Pain - Liver	0/31 (0%)		1/25 (4%)		1/71 (1.4%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/31 (3.2%)		0/25 (0%)		5/71 (7%)
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	1/31 (3.2%)		1/25 (4%)		5/71 (7%)
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Eye NOS	0/31 (0%)		1/25 (4%)		1/71 (1.4%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Joint	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Sinus	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Skin (cellulitis)	0/31 (0%)		2/25 (8%)		4/71 (5.6%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Ungual (nails)	1/31 (3.2%)		1/25 (4%)		2/71 (2.8%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Upper airway NOS	0/31 (0%)		1/25 (4%)		3/71 (4.2%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Vagina	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Infection with unknown ANC - Sinus	0/31 (0%)		1/25 (4%)		1/71 (1.4%)
Infection with unknown ANC - Skin (cellulitis)	0/31 (0%)		1/25 (4%)		1/71 (1.4%)
Injury, poisoning and procedural complications
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Fracture	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Investigations
Alkaline phosphatase	6/31 (19.4%)		6/25 (24%)		9/71 (12.7%)
ALT, SGPT (serum glutamic pyruvic transaminase)	1/31 (3.2%)		2/25 (8%)		5/71 (7%)
AST, SGOT(serum glutamic oxaloacetic transaminase)	2/31 (6.5%)		4/25 (16%)		6/71 (8.5%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	0/31 (0%)		1/25 (4%)		3/71 (4.2%)
Anorexia	6/31 (19.4%)		2/25 (8%)		17/71 (23.9%)
Calcium, serum-low (hypocalcemia)	0/31 (0%)		0/25 (0%)		4/71 (5.6%)
Creatinine	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Dehydration	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Glucose, serum-high (hyperglycemia)	1/31 (3.2%)		1/25 (4%)		5/71 (7%)
Magnesium, serum-low (hypomagnesemia)	3/31 (9.7%)		6/25 (24%)		10/71 (14.1%)
Metabolic/Laboratory - Other (Specify, __)	1/31 (3.2%)		1/25 (4%)		1/71 (1.4%)
Potassium, serum-low (hypokalemia)	1/31 (3.2%)		1/25 (4%)		10/71 (14.1%)
Sodium, serum-low (hyponatremia)	0/31 (0%)		1/25 (4%)		1/71 (1.4%)
Weight gain	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Joint-function	2/31 (6.5%)		1/25 (4%)		1/71 (1.4%)
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	0/31 (0%)		2/25 (8%)		1/71 (1.4%)
Musculoskeletal/Soft Tissue - Other (Specify, __)	4/31 (12.9%)		1/25 (4%)		3/71 (4.2%)
Pain - Back	0/31 (0%)		1/25 (4%)		13/71 (18.3%)
Pain - Bone	1/31 (3.2%)		1/25 (4%)		3/71 (4.2%)
Pain - Breast	1/31 (3.2%)		0/25 (0%)		3/71 (4.2%)
Pain - Buttock	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Pain - Extremity-limb	3/31 (9.7%)		4/25 (16%)		4/71 (5.6%)
Pain - Joint	4/31 (12.9%)		2/25 (8%)		10/71 (14.1%)
Pain - Muscle	3/31 (9.7%)		4/25 (16%)		7/71 (9.9%)
Pain - Neck	1/31 (3.2%)		0/25 (0%)		4/71 (5.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain - Tumor pain	0/31 (0%)		1/25 (4%)		1/71 (1.4%)
Nervous system disorders
Dizziness	4/31 (12.9%)		2/25 (8%)		9/71 (12.7%)
Memory impairment	2/31 (6.5%)		0/25 (0%)		3/71 (4.2%)
Neurology - Other (Specify, __)	0/31 (0%)		1/25 (4%)		3/71 (4.2%)
Neuropathy: motor	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Neuropathy: sensory	7/31 (22.6%)		3/25 (12%)		20/71 (28.2%)
Pain - Head/headache	10/31 (32.3%)		5/25 (20%)		7/71 (9.9%)
Taste alteration (dysgeusia)	1/31 (3.2%)		1/25 (4%)		4/71 (5.6%)
Tremor	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Psychiatric disorders
Insomnia	6/31 (19.4%)		2/25 (8%)		15/71 (21.1%)
Mood alteration - Anxiety	5/31 (16.1%)		2/25 (8%)		15/71 (21.1%)
Mood alteration - Depression	0/31 (0%)		2/25 (8%)		12/71 (16.9%)
Renal and urinary disorders
Cystitis	0/31 (0%)		0/25 (0%)		3/71 (4.2%)
Reproductive system and breast disorders
Breast function/lactation	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Vaginal dryness	1/31 (3.2%)		0/25 (0%)		4/71 (5.6%)
Respiratory, thoracic and mediastinal disorders
Cough	3/31 (9.7%)		3/25 (12%)		21/71 (29.6%)
Dyspnea (shortness of breath)	3/31 (9.7%)		6/25 (24%)		23/71 (32.4%)
Hemorrhage, pulmonary/upper respiratory - Nose	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Pain - Chest wall	2/31 (6.5%)		3/25 (12%)		4/71 (5.6%)
Pain - Chest/thorax NOS	2/31 (6.5%)		1/25 (4%)		3/71 (4.2%)
Pulmonary/Upper Respiratory - Other (Specify, __)	1/31 (3.2%)		0/25 (0%)		4/71 (5.6%)
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	2/31 (6.5%)		2/25 (8%)		5/71 (7%)
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Specify, __)	4/31 (12.9%)		2/25 (8%)		16/71 (22.5%)
Dry skin	7/31 (22.6%)		4/25 (16%)		18/71 (25.4%)
Hair loss/alopecia (scalp or body)	2/31 (6.5%)		0/25 (0%)		7/71 (9.9%)
Nail changes	3/31 (9.7%)		3/25 (12%)		7/71 (9.9%)
Pruritus/itching	3/31 (9.7%)		2/25 (8%)		7/71 (9.9%)
Rash/desquamation	9/31 (29%)		4/25 (16%)		15/71 (21.1%)
Rash: acne/acneiform	11/31 (35.5%)		10/25 (40%)		42/71 (59.2%)
Rash: dermatitis associated with radiation - Chemoradiation	1/31 (3.2%)		0/25 (0%)		1/71 (1.4%)
Rash: hand-foot skin reaction	2/31 (6.5%)		1/25 (4%)		6/71 (8.5%)
Sweating (diaphoresis)	2/31 (6.5%)		0/25 (0%)		1/71 (1.4%)
Vascular disorders
Flushing	0/31 (0%)		0/25 (0%)		2/71 (2.8%)
Hot flashes/flushes	6/31 (19.4%)		1/25 (4%)		12/71 (16.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.