ERBITUX® Followed by Adjuvant Treatment With Chemoradiation and ERBITUX® for Locally Advanced Head and Neck Squamous Cell Carcinoma

• Sponsor: Robert Ferris (Other)
• Overall Status: Completed
• CT.gov ID: NCT01218048
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 40
• Location: 1
• Arm: 1
• Duration (Months): 72.4
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

There are currently no useful tests to identify patients who will respond to cetuximab therapy, notably because EGFR levels do not correlate with the clinical responses observed. Thus, the investigators are investigating the role of cellular immunity and immune escape mechanisms to explain the differential clinical response to cetuximab.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of the Head and Neck	Drug: Cetuximab; Procedure: Surgery; Radiation: Post-surgical radiation; Drug: Cisplatin or carboplatin	Phase 2

Detailed Description

This prospective phase II clinical trial of preoperative, single-agent cetuximab treated patients is being conducted in order to obtain specimens before and after 4 weeks of cetuximab for immune biomarker studies. Stage III/IV HNC patients will be treated with definitive surgical resection and observed for disease recurrence. Cetuximab will be administered for a 3-4 week preoperative period to study biomarker modulation in correlation clinical response by CT scan and tumor apoptosis/proliferation after tumor excision, immediately after neoadjuvant cetuximab but before surgery. We will biopsy the skin/acneiform rash in all patients to correlate rash with biomarker modulation and clinical response. Cetuximab may also be given in the adjuvant setting. A primary scientific hypothesis will be tested: does short term pre-operative exposure to cetuximab modulate blood immune biomarkers and is immune modulation associated with anti-tumor effect? Forty (n=40) patients with complete specimens (tumor, peripheral blood mononuclear cells (PBMC) and serum) are necessary to enable adequate statistical power to be reached using paired specimens. A secondary set of hypotheses will evaluate the association between pre-operative biomarker levels and modulation with disease recurrence. The proposed trial will accrue stage II, III or IV surgical candidates without distant metastasis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Neoadjuvant Immune Biomarker Modulation With Cetuximab Followed by Adjuvant Therapy With Concurrent Chemoradiotherapy or Radiotherapy With or Without Cetuximab for Locally Advanced Head and Neck Squamous Cell Carcinoma
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Nov 4, 2015
• Actual Study Completion Date: Feb 14, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Neo-Adjuvant Cetuximab Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation + Cisplatin (or Carboplatin) NOTE: Based the results of surgery if the treating physician feels patient is not a candidate for chemotherapy, radiation can be given alone or with cetuximab.

Drug: Cetuximab; Pre-Surgery: IV, 400 mg/m2 day 1 then 250 mg/m2 alone days 8 and 15; Post-surgery: IV, 250 mg/m2 weekly concurrent with RT; Other Names: ERBITUX® ; Procedure: Surgery; Surgery for tumor; Radiation: Post-surgical radiation; Radiation (2 Gy/d) to min of 60 Gy + max of 66 Gy post-surgery; Drug: Cisplatin or carboplatin; Cisplatin 30 mg/m2 or carboplatin AUC 1.5-2/week weekly, Concurrent with radiotherapy

Outcome Measures

Primary Outcome Measures

1. NK Cell Activation [Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)]

   Cetuximab-mediated NK cell activation (percentage of activity) measures at pre-/post-cetuximab exposure for patients in peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) and in those patients that did and did not respond to treatment.

2. Serum Cytokines Levels [Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)]

   Serum cytokines levels measured at pre-/post-cetuximab, exposure measured in picogram per milliliter of plasma (pg/ml)

3. T Cell Activation [Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)]

   T cell activation measured at pre-/post-cetuximab exposure

Secondary Outcome Measures

1. Frequency of EGFR-specific T Cells (EGFR853-861 Peptide-specific Tetramer+ CD8+T Cells) [Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)]

   Difference in frequency of circulating EGFR-specific T cells between cetuximab-treated and cetuximab-naive patients

2. Progression-free Survival (PFS) [Up to 54 months]

   The length of time during and after study treatment that participants lived with disease that did not progress per RECIST 1.0. Progression per RECIST 1.0 is defined as a 20% increase the in longest dimension (LD) lesion from Nadir.

3. Overall Survival (OS) [Up to 2 years]

   Number of patients remaining alive.

4. Objective Response (Rate) [Up to 2 years]

   The percentage of participants that experienced a response to study treatment, per RECIST 1.0: Number of participant with (Complete Response (CR) + number of participants with Partial Response (PR) / Total number of participants evaluable for response.

5. 3-year Progression-free Survival (PFS) [3 years]

   Percentage of participants alive at 3 years that did not experience disease progression per RECIST 1.0. Progression per RECIST 1.0 is defined as a 20% increase the in longest dimension (LD) lesion from Nadir.

6. Change in Tumor Size [Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)]

   Largest percent change (decrease) in tumor size before and after neoadjuvant cetuximab.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed, previously untreated HNC. Clinical stage III or IVA disease without distant metastases as determined by CT, and as defined by the American Joint Committee on Cancer Staging System, Sixth edition (See Appendix I).

• Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx will be included. Primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or unknown primary tumors are NOT allowed.

• Macroscopic complete resection of the primary tumor must be planned.

• Age greater than or equal to 18 years.

• ECOG performance status 0-1.

• Adequate hematologic, renal and hepatic function, as defined by:

• Absolute neutrophil count (ANC) greater than or equal to 1,500/ul, platelets greater than or equal to 100,000/ul.

• Creatinine clearance > 40

• Bilirubin less than or equal to 1.5 x ULN, AST or ALT less than or equal to 2.5 x ULN.

• Have signed written informed consent.

Exclusion Criteria:

• Subjects who fail to meet the above criteria.

• Prior severe infusion reaction to a monoclonal antibody.

• Pregnancy or breastfeeding. Women of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.

• All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation. The Investigator must immediately notify BMS in the event of a confirmed pregnancy in a patient participating in the study.

• Subjects with an ECOG performance status of 2 or worse.

• Evidence of distant metastasis.

• Any other malignancy active within 5 years except for non-melanoma skin cancer or carcinoma in situ of the cervix, DCIS or LCIS of the breast.

• Prior history of HNC.

• Prior therapy targeting the EGFR pathway.

• Any unresolved chronic toxicity greater than or equal to grade 2 from previous anticancer therapy (except alopecia), according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE).

• Acute hepatitis, known HIV, or active uncontrolled infection.

• History of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within prior 6 months, untreated known coronary artery disease, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.

• Uncontrolled peptic or gastric ulcer disease, or gastrointestinal bleeding within prior 6 months.

• Active alcohol abuse or other illness that carries a likelihood of inability to comply with study treatment and follow-up.

• Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UPCI - Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232

Sponsors and Collaborators

• Robert Ferris
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Rober L Ferris, MD, PhD, University of Pittsburgh Med Ctr (UPCI)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert Ferris, MD, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT01218048
• Other Study ID Numbers: UPCI 08-013
• First Posted: Oct 8, 2010
• Last Update Posted: Aug 16, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Robert Ferris, MD, University of Pittsburgh: Carcinoma; Head and Neck; Cetuximab; Locally Advanced Head and Neck Squamous Cell Carcinoma
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carboplatin; Cetuximab

Study Results

Participant Flow

Arm/Group Title	Neo-Adjuvant Cetuximab
Arm/Group Description	Patients with Head and Neck Squamous Cell Cancer (HNSCC) treated with Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation + Cisplatin (or Carboplatin) NOTE: Based the results of surgery if the treating physician feels patient is not a candidate for chemotherapy, radiation can be given alone or with cetuximab. Cetuximab: Pre-Surgery: IV, 400 mg/m^2 day 1 then 250 mg/m^2 alone days 8 and 15; Post-surgery: IV, 250 mg/m2 weekly concurrent with RT Post-surgical radiation: Radiation (2 Gy/d) to min of 60 Gy + max of 66 Gy post-surgery Cisplatin or carboplatin: Cisplatin 30 mg/m2 or carboplatin AUC 1.5-2/week weekly, Concurrent with radiotherapy
Period Title: Overall Study
STARTED	40
COMPLETED	40
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Neo-Adjuvant Cetuximab
Arm/Group Description	Patients with Head and Neck Squamous Cell Cancer (HNSCC) treated with Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation + Cisplatin (or Carboplatin) NOTE: Based the results of surgery if the treating physician feels patient is not a candidate for chemotherapy, radiation can be given alone or with cetuximab. Cetuximab: Pre-Surgery: IV, 400 mg/m^2 day 1 then 250 mg/m^2 alone days 8 and 15; Post-surgery: IV, 250 mg/m2 weekly concurrent with RT Post-surgical radiation: Radiation (2 Gy/d) to min of 60 Gy + max of 66 Gy post-surgery Cisplatin or carboplatin: Cisplatin 30 mg/m2 or carboplatin AUC 1.5-2/week weekly, Concurrent with radiotherapy
Overall Participants	40
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	58.6
Sex: Female, Male (Count of Participants)
Female	10 25%
Male	30 75%

Outcome Measures

1. Primary Outcome

Title	NK Cell Activation
Description	Cetuximab-mediated NK cell activation (percentage of activity) measures at pre-/post-cetuximab exposure for patients in peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) and in those patients that did and did not respond to treatment.
Time Frame	Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

Outcome Measure Data

Analysis Population Description

Participants that received preoperative treatment with single-agent cetuximab for a minimum of 3-4 weeks.Patients defined as responders, demonstrated upregulation of CD137 on tumor infiltrating NK cells following cetuximab therapy compared with non-responders.

Arm/Group Title	Neo-Adjuvant Cetuximab
Arm/Group Description	Patients with Head and Neck Squamous Cell Cancer (HNSCC) treated with Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation +/- Cisplatin (or Carboplatin): Intravenous Cetuximab (pre-surgery) 400 mg/m^2 alone days 8 and 15; then 250mg/m^2/week) for 3-4 weeks preoperatively, followed post-surgery by adjuvant chemoradiation with or without 250 mg/m^2 weekly cetuximab.
Measure Participants	17
Percent NK cells (PBL): pre-cetuximab	19
Percent NK cells (PBL): post-cetuximab	20
Percent NK cells (TIL): pre-cetuximab	4
Percent NK cells (TIL): post-cetuximab	3
Percent CD16+ NK cells(PBL): pre-cetuximab	55
Percent CD16+ NK cells (PBL): post-cetuximab	49
Percent CD16+ NK cells (TIL): pre-cetuximab	10
Percent CD16+ NK cells (TIL): post-cetuximab	6
Percent Granzyme B+ cells (PBL): pre-cetuximab	54
Percent Granzyme B+ cells(PBL): post-cetuximab	64
Percent Granzyme B+ cells (TIL): pre-cetuximab	17
Percent Granzyme B+ cells (TIL): post-cetuximab	21
Percent Perforin+ cells (PBL): pre-cetuximab	50
Percent Perforin+ cells (PBL): post-cetuximab	60
Percent Perforin+ cells (TIL): pre-cetuximab	6
Percent Perforin+ cells (TIL): post-cetuximab	10
Percent CD107a+ cells (PBL): pre-cetuximab	1
Percent CD107a+ cells (PBL): post-cetuximab	0
Percent CD107a+ cells (TIL): pre-cetuximab	36
Percent CD107a+ cells (TIL): post-cetuximab	60
Percent CD137+ cells (PBL): pre-cetuximab	2
Percent CD137+ cells (PBL): post-cetuximab	0
Percent CD137+ cells (TIL): pre-cetuximab	6
Percent CD137+ cells (TIL): post-cetuximab	10

2. Primary Outcome

Title	Serum Cytokines Levels
Description	Serum cytokines levels measured at pre-/post-cetuximab, exposure measured in picogram per milliliter of plasma (pg/ml)
Time Frame	Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

Outcome Measure Data

Analysis Population Description

Participants that received preoperative treatment with single-agent cetuximab for a minimum of 3-4 weeks.

Arm/Group Title	Neo-Adjuvant Cetuximab
Arm/Group Description	Patients with Head and Neck Squamous Cell Cancer (HNSCC) treated with Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation +/- Cisplatin (or Carboplatin): Intravenous Cetuximab (pre-surgery) 400 mg/m^2 alone days 8 and 15; then 250mg/m^2/week) for 3-4 weeks preoperatively, followed post-surgery by adjuvant chemoradiation with or without 250 mg/m^2 weekly cetuximab.
Measure Participants	33
Responders: pre-cetuximab GM-CSF	2.5
Non-responders: pre-cetuximab GM-CSF	18.0
Responders: post-cetuximab GM-CSF	11.0
Non-responders: post-cetuximab GM-CSF	5.0
Responders: pre-cetuximab CCL2	260
Non-responders: pre-cetuximab CCL2	500
Responders: post-cetuximab CCL2	250
Non-responders: post-cetuximab CCL2	200
Responders: pre-cetuximab MP-1 alpha	6.0
Non-responders: pre-cetuximab MP-1 alpha	10.0
Responders: post-cetuximab MP-1 alpha	7.0
Non-responders: post-cetuximab MP-1 alpha	3.0

3. Primary Outcome

Title	T Cell Activation
Description	T cell activation measured at pre-/post-cetuximab exposure
Time Frame	Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

Outcome Measure Data

Analysis Population Description

Participants that received preoperative treatment with single-agent cetuximab for a minimum of 3-4 weeks.

Arm/Group Title	Neo-Adjuvant Cetuximab
Arm/Group Description	Patients with Head and Neck Squamous Cell Cancer (HNSCC) treated with Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation +/- Cisplatin (or Carboplatin): Intravenous Cetuximab (pre-surgery) 400 mg/m^2 alone days 8 and 15; then 250mg/m^2/week) for 3-4 weeks preoperatively, followed post-surgery by adjuvant chemoradiation with or without 250 mg/m^2 weekly cetuximab.
Measure Participants	33
Pre-cetuximab	0.25
Post-cetuximab	1.0

4. Secondary Outcome

Title	Frequency of EGFR-specific T Cells (EGFR853-861 Peptide-specific Tetramer+ CD8+T Cells)
Description	Difference in frequency of circulating EGFR-specific T cells between cetuximab-treated and cetuximab-naive patients
Time Frame	Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neo-Adjuvant Cetuximab
Arm/Group Description	Patients with Head and Neck Squamous Cell Cancer (HNSCC) treated with Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation +/- Cisplatin (or Carboplatin): Intravenous Cetuximab (pre-surgery) 400 mg/m^2 alone days 8 and 15; then 250mg/m^2/week) for 3-4 weeks preoperatively, followed post-surgery by adjuvant chemoradiation with or without 250 mg/m^2 weekly cetuximab.
Measure Participants	39
no cetuximab-treatment	45
cetuximab-treatment	120

5. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	The length of time during and after study treatment that participants lived with disease that did not progress per RECIST 1.0. Progression per RECIST 1.0 is defined as a 20% increase the in longest dimension (LD) lesion from Nadir.
Time Frame	Up to 54 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neo-Adjuvant Cetuximab
Arm/Group Description	Patients with Head and Neck Squamous Cell Cancer (HNSCC) treated with Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation +/- Cisplatin (or Carboplatin): Intravenous Cetuximab (pre-surgery) 400 mg/m^2 alone days 8 and 15; then 250mg/m^2/week) for 3-4 weeks preoperatively, followed post-surgery by adjuvant chemoradiation with or without 250 mg/m^2 weekly cetuximab.
Measure Participants	40
Median (Full Range) [months]	24

6. Secondary Outcome

Title	Overall Survival (OS)
Description	Number of patients remaining alive.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All patients enrolled in the study.

Arm/Group Title	Neo-Adjuvant Cetuximab
Arm/Group Description	Patients with Head and Neck Squamous Cell Cancer (HNSCC) treated with Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation + Cisplatin (or Carboplatin) NOTE: Based the results of surgery if the treating physician feels patient is not a candidate for chemotherapy, radiation can be given alone or with cetuximab. Cetuximab: Pre-Surgery: IV, 400 mg/m^2 day 1 then 250 mg/m^2 alone days 8 and 15; Post-surgery: IV, 250 mg/m2 weekly concurrent with RT Post-surgical radiation: Radiation (2 Gy/d) to min of 60 Gy + max of 66 Gy post-surgery Cisplatin or carboplatin: Cisplatin 30 mg/m2 or carboplatin AUC 1.5-2/week weekly, Concurrent with radiotherapy
Measure Participants	40
Number [participants]	40 100%

7. Secondary Outcome

Title	Objective Response (Rate)
Description	The percentage of participants that experienced a response to study treatment, per RECIST 1.0: Number of participant with (Complete Response (CR) + number of participants with Partial Response (PR) / Total number of participants evaluable for response.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Participant that where evaluable for response to treatment with cetuximab (400 mg/m2 then 250mg/m2/week) for 3-4 weeks preoperatively, followed by adjuvant chemoradiation with or without cetuximab.

Arm/Group Title	Neo-Adjuvant Cetuximab
Arm/Group Description	Patients with Head and Neck Squamous Cell Cancer (HNSCC) treated with Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation +/- Cisplatin (or Carboplatin): Intravenous Cetuximab (pre-surgery) 400 mg/m^2 alone days 8 and 15; then 250mg/m^2/week) for 3-4 weeks preoperatively, followed post-surgery by adjuvant chemoradiation with or without 250 mg/m^2 weekly cetuximab.
Measure Participants	33
Number [percentage of participants]	33 82.5%

8. Secondary Outcome

Title	3-year Progression-free Survival (PFS)
Description	Percentage of participants alive at 3 years that did not experience disease progression per RECIST 1.0. Progression per RECIST 1.0 is defined as a 20% increase the in longest dimension (LD) lesion from Nadir.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neo-Adjuvant Cetuximab
Arm/Group Description	Patients with Head and Neck Squamous Cell Cancer (HNSCC) treated with Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation +/- Cisplatin (or Carboplatin): Intravenous Cetuximab (pre-surgery) 400 mg/m^2 alone days 8 and 15; then 250mg/m^2/week) for 3-4 weeks preoperatively, followed post-surgery by adjuvant chemoradiation with or without 250 mg/m^2 weekly cetuximab.
Measure Participants	40
Number (95% Confidence Interval) [percentage of participants]	84 210%

9. Secondary Outcome

Title	Change in Tumor Size
Description	Largest percent change (decrease) in tumor size before and after neoadjuvant cetuximab.
Time Frame	Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neo-Adjuvant Cetuximab
Arm/Group Description	Patients with Head and Neck Squamous Cell Cancer (HNSCC) treated with Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation + Cisplatin (or Carboplatin) NOTE: Based the results of surgery if the treating physician feels patient is not a candidate for chemotherapy, radiation can be given alone or with cetuximab. Cetuximab: Pre-Surgery: IV, 400 mg/m^2 day 1 then 250 mg/m^2 alone days 8 and 15; Post-surgery: IV, 250 mg/m2 weekly concurrent with RT Post-surgical radiation: Radiation (2 Gy/d) to min of 60 Gy + max of 66 Gy post-surgery Cisplatin or carboplatin: Cisplatin 30 mg/m2 or carboplatin AUC 1.5-2/week weekly, Concurrent with radiotherapy
Measure Participants	16
Number [percent]	10

Adverse Events

Arm/Group Title	Neo-Adjuvant Cetuximab
Arm/Group Description	Patients with Head and Neck Squamous Cell Cancer (HNSCC) treated with Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation +/- Cisplatin (or Carboplatin): Intravenous Cetuximab (pre-surgery) 400 mg/m^2 alone days 8 and 15; then 250mg/m^2/week) for 3-4 weeks preoperatively, followed post-surgery by adjuvant chemoradiation with or without 250 mg/m^2 weekly cetuximab.
All Cause Mortality
	Neo-Adjuvant Cetuximab
	Affected / at Risk (%)	# Events
Total	32/40 (80%)
Serious Adverse Events
	Neo-Adjuvant Cetuximab
	Affected / at Risk (%)	# Events
Total	8/40 (20%)
Endocrine disorders
Hypothyroidism	1/40 (2.5%)
Gastrointestinal disorders
Constipation	1/40 (2.5%)
Mucositis oral	2/40 (5%)
Infections and infestations
Infections and infestations - Other, specify	1/40 (2.5%)
Soft tissue infection	1/40 (2.5%)
Injury, poisoning and procedural complications
Fall	2/40 (5%)
Postoperative hemorrhage	1/40 (2.5%)
Wound dehiscence	1/40 (2.5%)
Metabolism and nutrition disorders
Dehydration	1/40 (2.5%)
Hypoglycemia	1/40 (2.5%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	1/40 (2.5%)
Psychiatric disorders
Mania	1/40 (2.5%)
Vascular disorders
Thromboembolic event	1/40 (2.5%)
Other (Not Including Serious) Adverse Events
	Neo-Adjuvant Cetuximab
	Affected / at Risk (%)	# Events
Total	32/40 (80%)
Blood and lymphatic system disorders
Anemia	15/40 (37.5%)
Blood and lymphatic system disorders - Other, specify	5/40 (12.5%)
Leukocytosis	2/40 (5%)
Cardiac disorders
Sinus tachycardia	2/40 (5%)
Ear and labyrinth disorders
Hearing impaired	2/40 (5%)
Tinnitus	3/40 (7.5%)
Endocrine disorders
Hypothyroidism	2/40 (5%)
Eye disorders
Dry eye	2/40 (5%)
Gastrointestinal disorders
Constipation	12/40 (30%)
Diarrhea	5/40 (12.5%)
Dry mouth	12/40 (30%)
Dysphagia	18/40 (45%)
Esophageal pain	2/40 (5%)
Gastroesophageal reflux disease	4/40 (10%)
Gastrointestinal disorders - Other, specify	11/40 (27.5%)
Mucositis oral	15/40 (37.5%)
Nausea	13/40 (32.5%)
Oral pain	7/40 (17.5%)
Vomiting	7/40 (17.5%)
General disorders
Chills	3/40 (7.5%)
Edema face	2/40 (5%)
Fatigue	13/40 (32.5%)
Fever	3/40 (7.5%)
Flu like symptoms	2/40 (5%)
Pain	9/40 (22.5%)
Infections and infestations
Infections and infestations - Other, specify	6/40 (15%)
Skin infection	2/40 (5%)
Injury, poisoning and procedural complications
Dermatitis radiation	3/40 (7.5%)
Fall	3/40 (7.5%)
Investigations
Alanine aminotransferase increased	5/40 (12.5%)
Alkaline phosphatase increased	4/40 (10%)
Aspartate aminotransferase increased	6/40 (15%)
Cholesterol high	4/40 (10%)
Creatinine increased	2/40 (5%)
Investigations - Other, specify	3/40 (7.5%)
Lymphocyte count decreased	9/40 (22.5%)
Neutrophil count decreased	5/40 (12.5%)
Platelet count decreased	5/40 (12.5%)
Weight loss	19/40 (47.5%)
White blood cell decreased	9/40 (22.5%)
Metabolism and nutrition disorders
Anorexia	4/40 (10%)
Dehydration	9/40 (22.5%)
Hypercalcemia	3/40 (7.5%)
Hyperglycemia	16/40 (40%)
Hyperkalemia	2/40 (5%)
Hypermagnesemia	4/40 (10%)
Hypoalbuminemia	13/40 (32.5%)
Hypocalcemia	4/40 (10%)
Hypoglycemia	2/40 (5%)
Hypokalemia	6/40 (15%)
Hypomagnesemia	5/40 (12.5%)
Hyponatremia	11/40 (27.5%)
Hypophosphatemia	2/40 (5%)
Metabolism and nutrition disorders - Other, specify	2/40 (5%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/40 (5%)
Arthritis	4/40 (10%)
Generalized muscle weakness	3/40 (7.5%)
Musculoskeletal and connective tissue disorder - Other, specify	4/40 (10%)
Neck pain	2/40 (5%)
Nervous system disorders
Dizziness	3/40 (7.5%)
Dysgeusia	5/40 (12.5%)
Headache	16/40 (40%)
Psychiatric disorders
Anxiety	9/40 (22.5%)
Depression	5/40 (12.5%)
Insomnia	6/40 (15%)
Renal and urinary disorders
Renal calculi	2/40 (5%)
Respiratory, thoracic and mediastinal disorders
Cough	2/40 (5%)
Dyspnea	4/40 (10%)
Hoarseness	2/40 (5%)
Respiratory, thoracic and mediastinal disorders - Other, specify	2/40 (5%)
Voice alteration	5/40 (12.5%)
Skin and subcutaneous tissue disorders
Alopecia	2/40 (5%)
Dry skin	7/40 (17.5%)
Pruritus	7/40 (17.5%)
Rash acneiform	17/40 (42.5%)
Rash maculo-papular	3/40 (7.5%)
Skin and subcutaneous tissue disorders - Other, specify	19/40 (47.5%)
Vascular disorders
Hypertension	10/40 (25%)
Hypotension	5/40 (12.5%)

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.