Trial of 2 Cycles of Induction Chemo With Abraxane, Cetuximab, Cisplatin, & 5-FU for Advanced Head and Neck Cancer

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT00736944
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 30
• Location: 1
• Arms: 2
• Actual Duration (Months): 138.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase two trial will determine the tumor response rate at the primary site and at involved regional nodes to two cycles of an IC regimen of weekly Abraxane and cetuximab given in combination with cisplatin and 5-FU in patients with local regionally advanced HNSCC.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of the Head and Neck	Drug: Abraxane; Drug: Cetuximab; Drug: Cetuximab; Drug: Cisplatin; Drug: 5-FU; Radiation: Radiation (Post induction); Drug: Cisplatin; Drug: Cetuximab	Phase 2

Detailed Description

Primary objective:

To determine the clinical CR rate (CR-p) at the primary tumor site to an IC regimen of weekly Abraxane and cetuximab with CF (ACCF) given for two cycles (over 6 weeks) in patients with locally advanced non-metastatic HNSCC. The assessment of primary tumor site response will be performed by the treating physician by careful clinical examination using WHO criteria. Radiographic studies will also be performed to assess primary tumor site response but will be used primarily to confirm lack of disease progression that may not be detected based on clinical examination alone.

The secondary objectives include:

• Document the clinical PR rate (PR-p) at the primary tumor site with this IC regimen

• Document the clinical CR and PR rates at the involved regional nodes (CR-n and PR-n) with this IC regimen

• Document the clinical overall CR rate (CR-o) (defined as achievement of a CR at the primary tumor site and at the involved regional nodes) and the clinical overall PR rate (PR-o) with this IC regimen

• Document the CR (CR-p, CR-n, and CR-o) and PR (PR-p, PR-n, and PR-o) rates by FDG uptake on PET scan after this IC regimen

• Document radiographic CR (CR-p, CR-n, and CR-o) and PR (PR-p, PR-n, and PR-o) rates as assessed by conventional CT scan using RECIST criteria after this IC regimen.

• Correlate primary tumor site, nodal and overall tumor response rates based on WHO criteria of assessment with that based on CT scan and FDG-PET/CT.

• Document and quantify SPARC expression by IHC in primary tumor tissue obtained at baseline in each patient and attempt to correlate these results with primary tumor site response to ACCF.

• Document and grade AE's with this IC regimen with a pre-planned safety analysis after the first ten patients have completed the IC regimen.

• Determine the overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) of this patient population.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Trial to Determine the CR Rate at the Primary Tumor Site After 2 Cycles of Induction Chemo With Abraxane, Cetuximab, Cisplatin, & 5-FU for Advanced Head & Neck Carcinoma Treated With Definitive Concurrent Cisplatin & Radiation Therapy
• Actual Study Start Date: Dec 19, 2008
• Actual Primary Completion Date: Aug 31, 2010
• Actual Study Completion Date: Jul 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Induction chemotherapy followed by Radiation therapy plus Cisplatin Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42.	Drug: Abraxane; 100 mg/m2 IVPB, Day 1, 8 and 15 of cycles 1, 2, and 3; Drug: Cetuximab; 400 mg/m2 IVPB, Day 1, cycle 1; Drug: Cetuximab; 250 mg IVPB, Day 8 and 15 cycle 1, Day 1, 8 and 15 of cycles 2 and 3; Drug: Cisplatin; 75 mg/m2 IVPB Day 1, cycles 1, 2 and 3; Drug: 5-FU; 750 mg/m2 CIVI Day 1, 2 and 3, cycles 1, 2 and 3; Radiation: Radiation (Post induction); Monday-Friday, weeks 1-7; Drug: Cisplatin; (Post induction) Cisplatin 100 mg/m2 IVPB on radiation day 1, 22 and 42
Experimental: 2 Induction chemotherapy followed by Radiation therapy plus Cetuximab Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cetuximab (for patients who cannot receive cisplatin) will begin (+/- 3 days) before starting radiation therapy at 400 mg/m2 IVPB. Subsequent doses of cetuximab will be given weekly at 250 mg/m2 IVPB	Drug: Abraxane; 100 mg/m2 IVPB, Day 1, 8 and 15 of cycles 1, 2, and 3; Drug: Cetuximab; 400 mg/m2 IVPB, Day 1, cycle 1; Drug: Cetuximab; 250 mg IVPB, Day 8 and 15 cycle 1, Day 1, 8 and 15 of cycles 2 and 3; Drug: Cisplatin; 75 mg/m2 IVPB Day 1, cycles 1, 2 and 3; Drug: 5-FU; 750 mg/m2 CIVI Day 1, 2 and 3, cycles 1, 2 and 3; Radiation: Radiation (Post induction); Monday-Friday, weeks 1-7; Drug: Cetuximab; (Post-induction) Cetuximab (for patients who cannot receive cisplatin) will begin (+/- 3 days) before starting radiation therapy at 400 mg/m2 IVPB. Subsequent doses of cetuximab will be given weekly at 250 mg/m2 IVPB

Outcome Measures

Primary Outcome Measures

1. Clinical Complete Response Rate at the Primary Tumor [post-2 cycles of induction (approximately 42 days from start of treatment)]

   Clinical exam included laryngoscopy in office or operating room. Complete response rate includes complete response (CR) which is defined as 100% decrease in tumor size and it also includes near complete response (near CR) defined as 95-99% decrease in tumor size.

Secondary Outcome Measures

1. Clinical Partial Response Rate at the Primary Tumor [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

   Clinical exam included laryngoscopy in office or operating room. Partial response rate (PR) defined as 50% to 94% decrease in tumor size.

2. Clinical Complete and Partial Response Rates to the Involved Regional Nodes [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

   Clinical exam consisted of physical exam of neck in office. Complete response rate includes complete response (CR) which is defined as 100% decrease in tumor size and near complete response (near CR) defined as 95-99% decrease in tumor size. Partial response rate defined as 50% to 94% decrease in tumor size.

3. Clinical Overall Complete and Partial Response Rates [post-2 cycles of induction therapy (approximately 42 days)]

   Clinical exam included laryngoscopy in office or operating room. Clinical exam consisted of physical exam of neck in office. Complete response rate includes complete response (CR) which is defined as 100% decrease in tumor size and it also includes near complete response (near CR) defined as 95-99% decrease in tumor size. Partial response rate defined as 50% to 94% decrease in tumor size.

4. Complete and Partial Response Rates of Primary Tumor by FDG Uptake on PET Scan [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

   Complete response rate defined as complete resolution of the metabolically active primary tumor. Partial response rate defined as 20% or greater decrease in maximum SUV [SUV g/ml) = ROI activity (mCi/ml) / (injected dose (mCi/body weight(g))] from baseline. No unequivocal metabolic progression of non-target disease, and no unequivocal new lesions.

5. Complete and Partial Response Rates of Involved Lymph Nodes by FDG Uptake on PET Scan [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

   Complete response rate defined as complete resolution of the metabolically active primary tumor. Partial response rate defined as 20% or greater decrease in maximum SUV [SUV g/ml) = ROI activity (mCi/ml) / (injected dose (mCi/body weight(g))] from baseline. No unequivocal metabolic progression of non-target disease, and no unequivocal new lesions.

6. Radiographic Complete and Partial Response Rates of Primary Tumor as Assessed by Conventional CT Scan Using RECIST Criteria [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

   Complete response rate per RECIST criteria is defined as disappearance of all target lesions. Partial response rate per RECIST criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter.

7. Radiographic Complete and Partial Response Rates of Involved Lymph Nodes as Assessed by Conventional CT Scan Using RECIST Criteria [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

   Complete response rate per RECIST criteria is defined as disappearance of all target lesions. Partial response rate per RECIST criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter.

8. Radiographic Overall Complete and Partial Response Rates as Assessed by Conventional CT Scan Using RECIST Criteria [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

   Complete response rate per RECIST criteria is defined as disappearance of all target lesions. Partial response rate per RECIST criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter.

9. Correlate Primary Tumor Site Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

   In the future, primary tumor site, nodal, and OTR by VCR (CR-x or PR-x = Y or N) will be compared with response based on CT scan (CR-x or PR-x = Y or N) using a test for difference in paired, binary values. Median standardized uptake value of FDG measured by PET/CT will be compared among those with or without response (CR-x or PR-x) using nonparametric Wilcoxon-Mann-Whitney tests. We are releasing results based on comparing actual responses from visual categorical response, CT scan, and FDG-PET/CT scan after 2 cycles.

10. Correlate Nodal Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

    In the future, primary tumor site, nodal, and overall tumor response by visual categorical response (CR-x or PR-x = yes or no) will be compared with response based on CT scan (CR-x or PR-x = yes or no) using a test for difference in paired, binary values (e.g., McNemar's test). Median standardized uptake value of FDG measured by PET/CT will be compared among those with or without response (CR-x or PR-x) using nonparametric Wilcoxon-Mann-Whitney tests. At this point, we are releasing results based on comparing actual responses from visual categorical response, CT scan, and FDG-PET/CT scan after 2 cycles of induction.

11. Correlate Overall Tumor Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

    In the future, primary tumor site, nodal, and overall tumor response by visual categorical response (CR-x or PR-x = yes or no) will be compared with response based on CT scan (CR-x or PR-x = yes or no) using a test for difference in paired, binary values (e.g., McNemar's test). Median standardized uptake value of FDG measured by PET/CT will be compared among those with or without response (CR-x or PR-x) using nonparametric Wilcoxon-Mann-Whitney tests. At this point, we are releasing results based on comparing actual responses from visual categorical response, CT scan, and FDG-PET/CT scan after 2 cycles of induction.

12. Correlate SPARC Expression by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Complete Response Rate to Induction Chemotherapy [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

    SPARC expression = Proportion of tumor cells SPARC-positive in 10 high-power fields

13. Correlate SPARC Expression by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Partial Response Rate to Induction Chemotherapy [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

    SPARC expression = Proportion of tumor cells SPARC-positive in 10 high-power fields

14. Correlate SPARC Expression (Intensity of Staining) by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Complete Response Rate to Induction Chemotherapy [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

    SPARC expression = intensity of SPARC staining in tumor

15. Correlate SPARC Expression (Intensity of Staining) by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Partial Response Rate to Induction Chemotherapy [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

    SPARC expression = intensity of SPARC staining in tumor

16. Adverse Events Experienced During Induction Chemotherapy in the First Ten Patients for a Pre-planned Safety Analysis [completion of the first 10 patients induction chemotherapy]

17. Overall Survival [10 years from completion of treatment]

    Time from diagnosis to death or to last follow-up alive.

18. Disease Free Survival [10 years from completion of treatment]

    Time from complete response to death from any cause, to disease progression or to last follow-up alive.

19. Time to Progression [10 years from completion of treatment]

    Time from initiation of induction chemotherapy to death due to disease progression, to disease progression, or to last follow-up alive.

Other Outcome Measures

1. Overall Complete and Partial Response Rates by FDG Uptake on PET Scan [post-2 cycles of induction therapy (approximately 42 days from start of treatment)]

   Complete response rate defined as complete resolution of the metabolically active primary tumor. Partial response rate defined as 20% or greater decrease in maximum SUV [SUV g/ml) = ROI activity (mCi/ml) / (injected dose (mCi/body weight(g))] from baseline. No unequivocal metabolic progression of non-target disease, and no unequivocal new lesions.

Eligibility Criteria

Criteria

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

Inclusion

• Selected Stages 3 and 4a/b HNSCC: All patients must have T2-T4 primary tumors. Patients with T1 tumors will be excluded. Although most of these patients will have regional nodal disease, patients with no nodal disease will also be eligible.

• Oropharynx, hypopharynx, larynx, and oral cavity sub-sites only. Patients with nasopharyngeal, sinus and other sub-sites of the head and neck, or unknown primary SCC of the head and neck will NOT be eligible.

• Age ≥18 years

• Signed informed consent.

• ECOG Performance Status (PS) of 0-2 (Appendix 1).

• Adequate vital organ function (serum creatinine < 1.8 mg/dl, total bilirubin </= 1.5 mg/dl, ALT and AST </= 2.5 x ULN, alkaline phosphatase </= 2.5 x ULN) and hematopoietic function (ANC >/= 1500/ul, Platelets > 100,000/ul, HGB > 9.0 g/dl).

• Patients with reproductive potential must use an effective method of contraception to avoid pregnancy for the duration of the trial and for three months after completing treatment.

• If female of childbearing potential, the patient must have a negative pregnancy test.

Exclusion Criteria:

• Peripheral neuropathy > Grade 1.

• Prior chemotherapy, EGFR targeted therapy or radiation therapy for HNSCC.

• History of prior invasive malignancy diagnosed within the last three years other than local stage non-melanoma skin cancer.

• Be taking cimetidine or allopurinol. Patients must discontinue taking the medication for one week before receiving treatment with Abraxane.

• Be taking cimetidine or allopurinol. Patients must discontinue taking the medication for one week before receiving treatment with Abraxane.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• Celgene Corporation

Investigators

• Principal Investigator: Douglas Adkins, M.D., Washington Univerisity

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Publications

• Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA; Eastern Cooperative Oncology Group. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005 Dec 1;23(34):8646-54. Erratum in: J Clin Oncol. 2006 Feb 1;24(4):724.
• Department of Veterans Affairs Laryngeal Cancer Study Group, Wolf GT, Fisher SG, Hong WK, Hillman R, Spaulding M, Laramore GE, Endicott JW, McClatchey K, Henderson WG. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med. 1991 Jun 13;324(24):1685-90.
• Desai N, et al SABCS Dec, 2003
• Desai N, et al SABCS Dec, 2004
• Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. Epub 2005 Sep 19.
• Gradishar,et al SABCS 2006
• Hitt R, López-Pousa A, Martínez-Trufero J, Escrig V, Carles J, Rizo A, Isla D, Vega ME, Martí JL, Lobo F, Pastor P, Valentí V, Belón J, Sánchez MA, Chaib C, Pallarés C, Antón A, Cervantes A, Paz-Ares L, Cortés-Funes H. Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer. J Clin Oncol. 2005 Dec 1;23(34):8636-45. Epub 2005 Nov 7. Erratum in: J Clin Oncol. 2006 Feb 20;24(6):1015.
• JCO 12:1592, 1194
• Kato Y, Nagashima Y, Baba Y, Kawano T, Furukawa M, Kubota A, Yanoma S, Imagawa-Ishiguro Y, Satake K, Taguchi T, Hata R, Mochimatsu I, Aoki I, Kameda Y, Inayama Y, Tsukuda M. Expression of SPARC in tongue carcinoma of stage II is associated with poor prognosis: an immunohistochemical study of 86 cases. Int J Mol Med. 2005 Aug;16(2):263-8.
• Kies, et al ASCO 2006
• Kuperman, et al ASCO 2007
• Méndez E, Cheng C, Farwell DG, Ricks S, Agoff SN, Futran ND, Weymuller EA Jr, Maronian NC, Zhao LP, Chen C. Transcriptional expression profiles of oral squamous cell carcinomas. Cancer. 2002 Oct 1;95(7):1482-94.
• SABCS 2006
• Sparreboom A, van Zuylen L, Brouwer E, Loos WJ, de Bruijn P, Gelderblom H, Pillay M, Nooter K, Stoter G, Verweij J. Cremophor EL-mediated alteration of paclitaxel distribution in human blood: clinical pharmacokinetic implications. Cancer Res. 1999 Apr 1;59(7):1454-7.
• ten Tije AJ, Verweij J, Loos WJ, Sparreboom A. Pharmacological effects of formulation vehicles : implications for cancer chemotherapy. Clin Pharmacokinet. 2003;42(7):665-85. Review.
• van Tellingen O, Huizing MT, Panday VR, Schellens JH, Nooijen WJ, Beijnen JH. Cremophor EL causes (pseudo-) non-linear pharmacokinetics of paclitaxel in patients. Br J Cancer. 1999 Sep;81(2):330-5.
• Winer EP, Berry DA, Woolf S, Duggan D, Kornblith A, Harris LN, Michaelson RA, Kirshner JA, Fleming GF, Perry MC, Graham ML, Sharp SA, Keresztes R, Henderson IC, Hudis C, Muss H, Norton L. Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B trial 9342. J Clin Oncol. 2004 Jun 1;22(11):2061-8.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT00736944
• Other Study ID Numbers: 08-0911 / 201105501
• First Posted: Aug 18, 2008
• Last Update Posted: Sep 9, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Squamous Cell Carcinoma of Head and Neck; Cisplatin; Cetuximab; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Recruitment Details	Recruitment was open from 12/19/08-10/18/11 at the Siteman Cancer Center (a medical clinic).

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Period Title: Induction
STARTED	30
COMPLETED	29
NOT COMPLETED	1
Period Title: Induction
STARTED	29
COMPLETED	28
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	29 96.7%
>=65 years	1 3.3%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	54.5
Sex: Female, Male (Count of Participants)
Female	2 6.7%
Male	28 93.3%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Complete Response Rate at the Primary Tumor
Description	Clinical exam included laryngoscopy in office or operating room. Complete response rate includes complete response (CR) which is defined as 100% decrease in tumor size and it also includes near complete response (near CR) defined as 95-99% decrease in tumor size.
Time Frame	post-2 cycles of induction (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

All patients who completed 2 cycles of induction therapy.

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	30
Number [participants]	16 53.3%

2. Secondary Outcome

Title	Clinical Partial Response Rate at the Primary Tumor
Description	Clinical exam included laryngoscopy in office or operating room. Partial response rate (PR) defined as 50% to 94% decrease in tumor size.
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

Participants who completed 2 cycles of induction therapy

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	30
Number [participants]	14 46.7%

3. Secondary Outcome

Title	Clinical Complete and Partial Response Rates to the Involved Regional Nodes
Description	Clinical exam consisted of physical exam of neck in office. Complete response rate includes complete response (CR) which is defined as 100% decrease in tumor size and near complete response (near CR) defined as 95-99% decrease in tumor size. Partial response rate defined as 50% to 94% decrease in tumor size.
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

Twelve patients were not evaluable because of initial absence of nodal disease on clinical exam.

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	18
Complete response	11 36.7%
Partial response	7 23.3%

4. Secondary Outcome

Title	Clinical Overall Complete and Partial Response Rates
Description	Clinical exam included laryngoscopy in office or operating room. Clinical exam consisted of physical exam of neck in office. Complete response rate includes complete response (CR) which is defined as 100% decrease in tumor size and it also includes near complete response (near CR) defined as 95-99% decrease in tumor size. Partial response rate defined as 50% to 94% decrease in tumor size.
Time Frame	post-2 cycles of induction therapy (approximately 42 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	30
Overall complete response	13 43.3%
Overall partial response	17 56.7%

5. Secondary Outcome

Title	Complete and Partial Response Rates of Primary Tumor by FDG Uptake on PET Scan
Description	Complete response rate defined as complete resolution of the metabolically active primary tumor. Partial response rate defined as 20% or greater decrease in maximum SUV [SUV g/ml) = ROI activity (mCi/ml) / (injected dose (mCi/body weight(g))] from baseline. No unequivocal metabolic progression of non-target disease, and no unequivocal new lesions.
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

Two patients were not evaluable for this outcome. One patient's insurance company denied coverage for the PET scan so the PET scan was not performed. The other patient only had neck nodes that were clearly measurable on the PET scan, the primary site could not be measured on the PET scan.

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	28
Complete response	9 30%
Partial response	17 56.7%

6. Secondary Outcome

Title	Complete and Partial Response Rates of Involved Lymph Nodes by FDG Uptake on PET Scan
Description	Complete response rate defined as complete resolution of the metabolically active primary tumor. Partial response rate defined as 20% or greater decrease in maximum SUV [SUV g/ml) = ROI activity (mCi/ml) / (injected dose (mCi/body weight(g))] from baseline. No unequivocal metabolic progression of non-target disease, and no unequivocal new lesions.
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

Five patients were not evaluable for this outcome because these patients did not have any involved lymph nodes that could be measured.

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	25
Complete response	9 30%
Partial response	14 46.7%

7. Secondary Outcome

Title	Radiographic Complete and Partial Response Rates of Primary Tumor as Assessed by Conventional CT Scan Using RECIST Criteria
Description	Complete response rate per RECIST criteria is defined as disappearance of all target lesions. Partial response rate per RECIST criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter.
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

Two patients were not evaluable for this outcome. The first patient didn't have primary site disease that could be measured by RECIST. The second patient had primary site disease but it could not be clearly measured by CT. This disease was noted as a non-target lesion as present at baseline.

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	28
Complete response	10 33.3%
Partial response	11 36.7%

8. Secondary Outcome

Title	Radiographic Complete and Partial Response Rates of Involved Lymph Nodes as Assessed by Conventional CT Scan Using RECIST Criteria
Description	Complete response rate per RECIST criteria is defined as disappearance of all target lesions. Partial response rate per RECIST criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter.
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

Six patients were not evaluable for this outcome. Five of these patients did not have any involved lymph nodes available to evaluate. The sixth patient did not have involved lymph nodes that were clearly measurable by CT and RECIST.

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	24
Complete response	7 23.3%
Partial response	12 40%

9. Secondary Outcome

Title	Radiographic Overall Complete and Partial Response Rates as Assessed by Conventional CT Scan Using RECIST Criteria
Description	Complete response rate per RECIST criteria is defined as disappearance of all target lesions. Partial response rate per RECIST criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter.
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

One patient was not evaluable for this outcome. This patient had primary site disease that could not be clearly measured per CT and was listed as a non-target lesion.

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	29
Overall complete response	4 13.3%
Overall partial response	14 46.7%

10. Secondary Outcome

Title	Correlate Primary Tumor Site Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT
Description	In the future, primary tumor site, nodal, and OTR by VCR (CR-x or PR-x = Y or N) will be compared with response based on CT scan (CR-x or PR-x = Y or N) using a test for difference in paired, binary values. Median standardized uptake value of FDG measured by PET/CT will be compared among those with or without response (CR-x or PR-x) using nonparametric Wilcoxon-Mann-Whitney tests. We are releasing results based on comparing actual responses from visual categorical response, CT scan, and FDG-PET/CT scan after 2 cycles.
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

2 patients were not evaluable for the CT Scan of this outcome because they did not have primary disease that could be measured per RECIST. 2 patients were not evaluable for PET scan of this outcome because one patient's insurance company denied coverage and the other patient did not have primary site disease.

Arm/Group Title	Clinical Examination	CT Scan	FDG-PET/CT
Arm/Group Description
Measure Participants	30	28	28
Complete Response	53 176.7%	33 NaN	32 NaN
Partial Response	47 156.7%	41 NaN	61 NaN
Stable Disease/Progressive Disease	0 0%	26 NaN	7 NaN

11. Secondary Outcome

Title	Correlate Nodal Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT
Description	In the future, primary tumor site, nodal, and overall tumor response by visual categorical response (CR-x or PR-x = yes or no) will be compared with response based on CT scan (CR-x or PR-x = yes or no) using a test for difference in paired, binary values (e.g., McNemar's test). Median standardized uptake value of FDG measured by PET/CT will be compared among those with or without response (CR-x or PR-x) using nonparametric Wilcoxon-Mann-Whitney tests. At this point, we are releasing results based on comparing actual responses from visual categorical response, CT scan, and FDG-PET/CT scan after 2 cycles of induction.
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

12 patients were not evaluable for VSR because they did not have nodal disease. 6 patients were not evaluable for CT scan because 5 patients did not have nodal disease and 1 patient didn't have measurable nodal disease. 5 patients were not evaluable for PET because 5 patients did not have nodal disease.

Arm/Group Title	Clinical Examination	CT Scan	FDG-PET/CT
Arm/Group Description
Measure Participants	18	24	25
Complete Response	61 203.3%	30 NaN	36 NaN
Partial Response	39 130%	48 NaN	56 NaN
Stable Disease/Progressive Disease	0 0%	22 NaN	8 NaN

12. Secondary Outcome

Title	Correlate Overall Tumor Response Rates Based on Visual Categorical Criteria of Assessment With That Based on CT Scan and FDG-PET/CT
Description	In the future, primary tumor site, nodal, and overall tumor response by visual categorical response (CR-x or PR-x = yes or no) will be compared with response based on CT scan (CR-x or PR-x = yes or no) using a test for difference in paired, binary values (e.g., McNemar's test). Median standardized uptake value of FDG measured by PET/CT will be compared among those with or without response (CR-x or PR-x) using nonparametric Wilcoxon-Mann-Whitney tests. At this point, we are releasing results based on comparing actual responses from visual categorical response, CT scan, and FDG-PET/CT scan after 2 cycles of induction.
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

1 patient was not evaluable for CT scan because the primary site could not be clearly measured and was noted as non-target lesion. 1 patient was not evaluable for PET scan because the patient's insurance company denied coverage.

Arm/Group Title	Clinical Examination	CT Scan	FDG-PET/CT
Arm/Group Description
Measure Participants	30	29	29
Complete Response	43 143.3%	14 NaN	24 NaN
Partial Response	57 190%	50 NaN	66 NaN
Stable Disease/Progressive Disease	0 0%	36 NaN	10 NaN

13. Secondary Outcome

Title	Correlate SPARC Expression by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Complete Response Rate to Induction Chemotherapy
Description	SPARC expression = Proportion of tumor cells SPARC-positive in 10 high-power fields
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

Patients who had available tumor tissue for SPARC testing and were complete responders.

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	15
Negative staining	14 46.7%
1+ staining (0%-24%)	0 0%
2+ staining (25%-49%)	1 3.3%
3+ staining (50%-74%)	0 0%
4+ staining (75%-100%)	0 0%

14. Secondary Outcome

Title	Correlate SPARC Expression by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Partial Response Rate to Induction Chemotherapy
Description	SPARC expression = Proportion of tumor cells SPARC-positive in 10 high-power fields
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

Patients who had available tumor tissue for SPARC testing and were partial responders.

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	13
Negative staining	6 20%
1+ staining (0%-24%)	4 13.3%
2+ staining (25%-49%)	1 3.3%
3+ staining (50%-74%)	2 6.7%
4+ staining (75%-100%)	0 0%

15. Secondary Outcome

Title	Correlate SPARC Expression (Intensity of Staining) by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Complete Response Rate to Induction Chemotherapy
Description	SPARC expression = intensity of SPARC staining in tumor
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

Patients who had available tumor tissue for SPARC testing and were complete responders.

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	15
Negative staining	14 46.7%
1+ staining (weak)	0 0%
2+ staining (moderate)	1 3.3%
3+ staining (strong)	0 0%

16. Secondary Outcome

Title	Correlate SPARC Expression (Intensity of Staining) by Immunohistochemistry (IHC) in Baseline Primary Tumor Tissue With Primary Tumor Site Partial Response Rate to Induction Chemotherapy
Description	SPARC expression = intensity of SPARC staining in tumor
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

Patients who had available tumor tissue for SPARC testing and were partial responders.

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	13
Negative staining	6 20%
1+ staining (weak)	2 6.7%
2+ staining (moderate)	4 13.3%
3+ staining (strong)	1 3.3%

17. Secondary Outcome

Title	Adverse Events Experienced During Induction Chemotherapy in the First Ten Patients for a Pre-planned Safety Analysis
Time Frame	completion of the first 10 patients induction chemotherapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	10
Allergic reaction/hypersensitivity	1 3.3%
Other allergic reaction:cipro	1 3.3%
Other allergic reaction:hives	1 3.3%
Hypotension	1 3.3%
INR	1 3.3%
Fatigue	10 33.3%
Alopecia	5 16.7%
Chelitis	1 3.3%
Dry skin	1 3.3%
Rash	1 3.3%
Rash:acneiform	7 23.3%
Rash:penile (unconfirmed HSV)	1 3.3%
Anorexia	1 3.3%
Colitis	2 6.7%
Constipation	1 3.3%
Dehydration	1 3.3%
Dental:teeth	1 3.3%
Diarrhea	1 3.3%
Hemorrhoids	1 3.3%
Nausea	9 30%
Taste alteration	1 3.3%
Vomiting	1 3.3%
Other:soft stools	1 3.3%
Hemoglobin	8 26.7%
Leukocytes (WBC)	8 26.7%
Lymphopenia	8 26.7%
Neutrophils (ANC)	8 26.7%
Platelets	2 6.7%
Hemmorrhage:nose	1 3.3%
Alkaline phosphatase	3 10%
SGPT (ALT)	2 6.7%
Infection other:sinus infection	1 3.3%
Edema:limb	2 6.7%
Albumin, low	1 3.3%
Calcium, low	5 16.7%
Magnesium, low	4 13.3%
Potassium, low	3 10%
Potassium, high	2 6.7%
Sodium, low	3 10%
Phosphorus	1 3.3%
Dizziness	1 3.3%
Mood alteration:anger	1 3.3%
Neuropathy:sensory (peripheral)	1 3.3%
Vision-photophobia	1 3.3%
Pain:thigh	1 3.3%
Pain:tumor pain	1 3.3%
Hiccoughs (hiccups)	1 3.3%
Obstruction/stenosis of airway:trachea	2 6.7%
Creatinine	4 13.3%
GFR	2 6.7%
Renal failure	1 3.3%
Thrombosis/thrombus/embolism	1 3.3%

18. Secondary Outcome

Title	Overall Survival
Description	Time from diagnosis to death or to last follow-up alive.
Time Frame	10 years from completion of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	30
Mean (Standard Error) [months]	83.960 (5.384)

19. Secondary Outcome

Title	Disease Free Survival
Description	Time from complete response to death from any cause, to disease progression or to last follow-up alive.
Time Frame	10 years from completion of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	30
Mean (Standard Error) [months]	93.529 (3.462)

20. Secondary Outcome

Title	Time to Progression
Description	Time from initiation of induction chemotherapy to death due to disease progression, to disease progression, or to last follow-up alive.
Time Frame	10 years from completion of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	30
Mean (Standard Error) [months]	38.675 (1.485)

21. Other Pre-specified Outcome

Title	Overall Complete and Partial Response Rates by FDG Uptake on PET Scan
Description	Complete response rate defined as complete resolution of the metabolically active primary tumor. Partial response rate defined as 20% or greater decrease in maximum SUV [SUV g/ml) = ROI activity (mCi/ml) / (injected dose (mCi/body weight(g))] from baseline. No unequivocal metabolic progression of non-target disease, and no unequivocal new lesions.
Time Frame	post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Outcome Measure Data

Analysis Population Description

One patient was not evaluable for this outcome. This patient's insurance company denied coverage for the post-cycle 2 timepoint and because of this was not included in this overall response rate for PET scan.

Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
Measure Participants	29
Overall complete response	7 23.3%
Overall partial response	19 63.3%

Adverse Events

Time Frame	From time of consent through completion of induction chemotherapy.
Adverse Event Reporting Description	Serious adverse events are events grade 3 or higher. Lab results, treatment records, and dictations reviewed weekly.
Arm/Group Title	Induction Chemo + RT + Cisplatin or Cetuximab
Arm/Group Description	Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42 or Cetuximab 250 mg/m2 IVPB weekly Q8W.
All Cause Mortality
	Induction Chemo + RT + Cisplatin or Cetuximab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Induction Chemo + RT + Cisplatin or Cetuximab
	Affected / at Risk (%)	# Events
Total	19/30 (63.3%)
Cardiac disorders
Supraventricular and nodal arrhythmia: atrial fibrillation	1/30 (3.3%)	1
Cardiac ischemia	1/30 (3.3%)	1
Pain:chest	1/30 (3.3%)	1
Gastrointestinal disorders
Colitis	1/30 (3.3%)	1
Diarrhea	1/30 (3.3%)	1
Nausea	1/30 (3.3%)	1
Mucositis	1/30 (3.3%)	1
General disorders
Fatigue	3/30 (10%)	3
Immune system disorders
Allergic reaction/hypersensitivity	1/30 (3.3%)	1
Infections and infestations
Infection with normal ANC-rectal abscess	1/30 (3.3%)	1
Infection with grade 4 neutrophils:lung-pneumonia	1/30 (3.3%)	1
Investigations
Leukocytes (WBC)	3/30 (10%)	3
Lymphopenia	4/30 (13.3%)	4
Neutrophils (ANC)	5/30 (16.7%)	5
Platelets	1/30 (3.3%)	1
Hemoglobin	1/30 (3.3%)	1
Metabolism and nutrition disorders
Dehydration	1/30 (3.3%)	1
Calcium, low	2/30 (6.7%)	2
Potassium, low	3/30 (10%)	3
Sodium, low	1/30 (3.3%)	1
Phosphorus, low	1/30 (3.3%)	1
Albumin, low	1/30 (3.3%)	1
Glucose, high	1/30 (3.3%)	1
Nervous system disorders
Cerebrovascular ischemia	1/30 (3.3%)	1
Renal and urinary disorders
Renal failure	1/30 (3.3%)	1
Skin and subcutaneous tissue disorders
Rash: acneiform	4/30 (13.3%)	4
Vascular disorders
Thrombosis/thrombus/embolism	1/30 (3.3%)	1
Thrombosis/thrombus/embolism-vascular access device	4/30 (13.3%)	4
Other (Not Including Serious) Adverse Events
	Induction Chemo + RT + Cisplatin or Cetuximab
	Affected / at Risk (%)	# Events
Total	30/30 (100%)
Blood and lymphatic system disorders
Hemorrhage:nose	3/30 (10%)	3
Gastrointestinal disorders
Constipation	7/30 (23.3%)	7
Dental:teeth	2/30 (6.7%)	2
Diarrhea	13/30 (43.3%)	13
Heartburn	3/30 (10%)	3
Mucositis	6/30 (20%)	6
Nausea	19/30 (63.3%)	19
Vomiting	5/30 (16.7%)	5
General disorders
Fatigue	19/30 (63.3%)	19
Edema:limb	3/30 (10%)	3
Immune system disorders
Allergic reaction/hypersensitivity	2/30 (6.7%)	2
Investigations
INR	3/30 (10%)	3
PTT	2/30 (6.7%)	2
Weight loss	2/30 (6.7%)	2
Hemoglobin	26/30 (86.7%)	26
Leukocytes (WBC)	21/30 (70%)	21
Lymphopenia	16/30 (53.3%)	16
Neutrophils (ANC)	15/30 (50%)	15
Platelets	8/30 (26.7%)	8
Alkaline phosphatase	6/30 (20%)	6
SGOT (AST)	3/30 (10%)	3
SGPT (ALT)	10/30 (33.3%)	10
Magnesium, low	9/30 (30%)	9
Potassium, low	5/30 (16.7%)	5
Potassium, high	3/30 (10%)	3
Sodium, low	6/30 (20%)	6
Creatinine	7/30 (23.3%)	7
Metabolism and nutrition disorders
Albumin, low	6/30 (20%)	6
Calcium, low	11/30 (36.7%)	11
Glucose, high	5/30 (16.7%)	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain:tumor pain	3/30 (10%)	3
Nervous system disorders
Dizziness	3/30 (10%)	3
Neuropathy:sensory (peripheral)	6/30 (20%)	6
Renal and urinary disorders
GFR	2/30 (6.7%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/30 (6.7%)	2
Hiccoughs (hiccups)	2/30 (6.7%)	2
Skin and subcutaneous tissue disorders
Alopecia	11/30 (36.7%)	11
Rash:acneiform	20/30 (66.7%)	20
Rash:penile (unconfirmed HSV)	2/30 (6.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.