Palifermin in Lessening Oral Mucositis in Patients Undergoing Radiation Therapy and Chemotherapy for Locally Advanced Head and Neck Cancer

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00360971
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 21
• Locations: 48
• Arms: 2
• Duration (Months): 31.1
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Growth factors, such as palifermin, may lessen the severity of mucositis, or mouth sores, in patients receiving radiation therapy and chemotherapy for head and neck cancer. It is not yet known whether palifermin is more effective than a placebo in lessening mucositis in patients receiving radiation therapy and chemotherapy for head and neck cancer.

PURPOSE: This randomized phase III trial is studying palifermin to see how well it works compared to a placebo in lessening oral mucositis in patients undergoing radiation therapy and chemotherapy for locally advanced head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer; Mucositis; Pain; Radiation Toxicity	Biological: palifermin; Drug: cisplatin; Other: placebo; Procedure: neck dissection; Radiation: radiation therapy	Phase 3

Detailed Description

OBJECTIVES:

Primary

• Compare the efficacy of palifermin vs placebo, in terms of burden of acute mucositis (defined to be 105 days [15 weeks] or less from the start of treatment), in patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing concurrent radiotherapy and chemotherapy.

Secondary

• Compare incidence and time to onset of Grades 3 or 4 oral mucositis in patients treated with these regimens.

• Compare overall and progression-free survival and time to second primary in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease stage (III vs IVA or IVB), tumor site (oral cavity or oropharynx vs hypopharynx or larynx), and radiotherapy technique used on study (intensity-modulated radiotherapy [IMRT] vs 3-dimensional conformal radiotherapy [3D-CRT]). Patients are randomized to 1 of 2 treatment arms.

Mucositis, pain, and symptom burden are assessed at baseline, during radiotherapy, and post radiotherapy. Xerostomia is assessed at baseline, during radiotherapy, and several times after completion of study therapy.

After completion of study therapy, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 298 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: A Randomized, Phase III, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Palifermin (NSC# 740548; IND # 6370) for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer Receiving Radiation Therapy With Concurrent Chemotherapy (Followed by Surgery for Selected Patients)
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Palifermin Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.	Biological: palifermin; Four doses of palifermin, 180ųg/kg, administered as an i.v. bolus injection over 30-60 seconds. Starting on day -3 (Friday) prior to radiation therapy / chemotherapy and then once weekly, on days 5, 12, and 19.; Drug: cisplatin; Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.; Procedure: neck dissection; A neck dissection is required for patients with persistent nodal disease, any stage, if a palpable abnormality or worrisome radiographic abnormality persists in the neck 8-9 weeks after completion of therapy. A neck dissection is optional for patients with multiple positive lymph nodes or with lymph nodes exceeding 3 cm in diameter at pre-treatment (N2a, N2b, N3) who achieve a complete clinical and radiographic response in the neck. All patients will be assessed at approximately 8 weeks post-treatment with CT scan or MRI by the same technique used at baseline.; Radiation: radiation therapy; A radiation dose of 70 Gy with at least 66 Gy to at least 2 mucosal sites of the oral cavity/oropharynx mucosa. Radiation therapy can be given with 3D conformal (3D-CRT) or with intensity modulated RT (IMRT) techniques; however, the chosen modality must be used for the entire course of treatment.
Placebo Comparator: Placebo Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.	Drug: cisplatin; Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.; Other: placebo; Four doses of placebo, 180ųg/kg, administered as an i.v. bolus injection over 30-60 seconds. Starting on day -3 (Friday) prior to radiation therapy / chemotherapy and then once weekly, on days 5, 12, and 19.; Procedure: neck dissection; A neck dissection is required for patients with persistent nodal disease, any stage, if a palpable abnormality or worrisome radiographic abnormality persists in the neck 8-9 weeks after completion of therapy. A neck dissection is optional for patients with multiple positive lymph nodes or with lymph nodes exceeding 3 cm in diameter at pre-treatment (N2a, N2b, N3) who achieve a complete clinical and radiographic response in the neck. All patients will be assessed at approximately 8 weeks post-treatment with CT scan or MRI by the same technique used at baseline.; Radiation: radiation therapy; A radiation dose of 70 Gy with at least 66 Gy to at least 2 mucosal sites of the oral cavity/oropharynx mucosa. Radiation therapy can be given with 3D conformal (3D-CRT) or with intensity modulated RT (IMRT) techniques; however, the chosen modality must be used for the entire course of treatment.

Outcome Measures

Primary Outcome Measures

1. Duration of Oral Mucositis as Measured in Terms of Days [Twice-weekly from start of treatment up to 15 weeks after the start of treatment.]

   Duration in days of World Heath Organization (WHO) Grades 3 and 4 oral mucositis during the acute period (defined to be 105 days [15 weeks] or less from the start of treatment); duration is calculated from the onset of a Grade 3 or 4 oral mucositis to the day when an oral mucositis of ≤ Grade 2 is reported after the last oral mucositis of Grade 3 or 4. Patients with grade 0-2 mucositis have a duration of 0. This study required 298 patients to detect via two-sided t-test a reduction of mean duration of at least 9 days from 29 days (standard deviation = 23 days) on the placebo arm with 90% power and alpha = 0.05. Statistical testing was not done due to the small sample size.

Secondary Outcome Measures

1. Number of Patients With Grade 3 or 4 Mucositis as Measured by the World Heath Organization (WHO) Scale [Twice-weekly from start of treatment up to 15 weeks after the start of treatment.]

   Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

2. Time to Onset of Grade 3 or 4 Oral Mucositis as Measured by the World Heath Organization (WHO) Scale [Twice-weekly from start of treatment up to 15 weeks after the start of treatment.]

   Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

3. Overall Survival [From randomization to maximum follow-up at time of analysis of 21 months]

   An event is death from any cause. Overall survival was not calculated due to the limited number of events. Number of patients with an event is reported.

4. Progression-free Survival [From randomization to maximum follow-up at time of analysis of 21 months]

   An event is defined as the first occurrence of local, regional, distant disease. Progression-free survival is calculated at the time from registration to the death of progression, death in the absence of progression, or last follow-up. Progression-free survival was not calculated due to the limited number of events. Number of patients with an event is reported.

5. Time to Second Primary Tumor [From randomization to maximum follow-up at time of analysis of 21 months]

   An event is occurrence of a second primary other than basal cell. Time to second primary tumor was not calculated because there were no events. Number of patients with an event is reported.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph nodes) diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx;

2. Patients must have at least 2 mucosal sites of the oral cavity/oropharynx mucosa assessable by visual transoral inspection that will receive at least 66 Gy;

-2.1 Patients with tumors of the larynx or hypolarynx are eligible only if it is anticipated that the 2 index sites in the oral cavity/oropharynx mucosa will receive at least 66 Gy;

1. Patients must be able to be evaluated for the primary endpoint; therefore, patients must be able to eat at least soft solids and not require a feeding tube for nutrition or hydration at study entry.

2. Selected Stage III (excluding T1N1MO) or IVA-B (AJCC, 6th edition) at study entry, including no distant metastases, based upon the following minimum diagnostic workup:

• 4.1 History/physical examination, including documentation of tobacco/alcohol use and current medications (including opioids/dosing), within 8 weeks prior to registration;

• 4.2 Chest x-ray (or Chest CT scan) within 6 weeks prior to registration;

• 4.3 MRI or CT scan with contrast of tumor site within 6 weeks prior to registration;

• 4.4 Assessment of mucositis and xerostomia within 2 weeks prior to registration;

1. Zubrod Performance Status 0-1;

2. Age > 18;

3. Adequate bone marrow function, defined as follows:

• 7.1 Absolute neutrophil count (ANC) > 1,800 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study

• 7.2 Platelets > 100,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study

• 7.3 Hemoglobin > 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to registration on study (Note: The use of transfusion or other intervention to achieve Hgb > 8.0 g/dl is acceptable.)

1. Adequate hepatic function with bilirubin < 1.5 mg/dl, AST or ALT < 2 x ULN within 2 weeks prior to registration;

2. Adequate renal function with serum creatinine < 1.5 mg/dl and creatinine clearance (CC) ≥ 50 ml/min within 2 weeks prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula:

CCr male = [(140 - age) x (wt in kg)]/[(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male)

1. Normal serum calcium or normal corrected serum calcium within 2 weeks prior to registration; formula for corrected calcium if albumin valued is below normal range: Corrected calcium (mg/dl) = (4 - [patient's albumin (g/dl)] x 0.8) + patient's measured calcium (mg/dl);

2. Serum pregnancy test for women of childbearing potential within 2 weeks prior to registration;

3. Women of childbearing potential and male participants must practice adequate contraception.

4. Patient agrees to refrain from using all products listed in Section 9.2, "Non-permitted Supportive Therapy";

5. Patient must sign study specific informed consent prior to study entry.

Exclusion Criteria:

1. Patients with a history of prior head and neck squamous cancer are ineligible;

2. Stage IVC (AJCC, 6th edition) [Any T, Any N, M1] or distant metastases at protocol study entry; T1N1M0 patients are excluded.

3. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years;

4. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable. See Sections 1 and 3.

5. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;

6. Initial surgical treatment, excluding diagnostic biopsy of the primary site or nodal sampling of neck disease; radical or modified neck dissection is not permitted.

7. Severe, active co-morbidity, defined as follows:

• 7.1 Symptomatic and/or uncontrolled cardiac disease, New York Heart Association Classification III or IV (see Appendix II);

• 7.2 Transmural myocardial infarction within the last 6 months;

• 7.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;

• 7.4 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.

• 7.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;

• 7.6 Patients known to be sero-positive for hepatitis B virus (HBV) or hepatitis C virus (HCV);

• 7.7 Patients known to be sero-positive for human immunodeficiency virus (HIV) or patients with Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with HIV or AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.

• 7.8 A history of pancreatitis.

1. Collagen vascular disease, such as scleroderma, as this disease is thought to predispose patients to increased risk for radiation-associated toxicities;

2. Previous treatment with palifermin or other keratinocyte growth factors, such as velafermin or repifermin;

3. Prior allergic reaction or known sensitivity to any of the agents administered during dosing, including E. coli-derived products, such as Nutropin®, Neupogen®, Humulin®, Roferon®; Neumega®, Neulasta®), IntronA®, Betaseron®;

4. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Auburn Radiation Oncology	Auburn	California	United States	95603
3	Providence Saint Joseph Medical Center - Burbank	Burbank	California	United States	91505
4	Radiation Oncology Centers - Cameron Park	Cameron Park	California	United States	95682
5	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California	United States	95608
6	Enloe Cancer Center at Enloe Medical Center	Chico	California	United States	95926
7	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
8	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
9	Radiation Oncology Center - Roseville	Roseville	California	United States	95661
10	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California	United States	95815
11	Mercy General Hospital	Sacramento	California	United States	95819
12	Torrance Memorial Medical Center	Torrance	California	United States	90509
13	Solano Radiation Oncology Center	Vacaville	California	United States	95687
14	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
15	Saint John's Cancer Center at Saint John's Medical Center	Anderson	Indiana	United States	46016
16	St. Agnes Hospital Cancer Center	Baltimore	Maryland	United States	21229
17	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
18	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
19	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
20	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
21	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
22	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
23	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
24	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
25	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi	United States	39581
26	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
27	Cancer Institute of New Jersey at Cooper University Hospital - Camden	Camden	New Jersey	United States	08103
28	Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare	Vineland	New Jersey	United States	08360
29	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
30	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
31	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina	United States	27835-6028
32	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
33	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
34	Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford	Salem	Ohio	United States	44460
35	Cancer Treatment Center	Wooster	Ohio	United States	44691
36	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
37	Sharon Regional Cancer Care Center- Hermitage	Hermitage	Pennsylvania	United States	16148
38	Intercommunity Cancer Center	Monroeville	Pennsylvania	United States	15146
39	Alle-Kiski Medical Center	Natrona Heights	Pennsylvania	United States	15065
40	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
41	Somerset Oncology Center	Somerset	Pennsylvania	United States	15501
42	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
43	Johnson City Medical Center Hospital	Johnson City	Tennessee	United States	37604
44	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
45	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia	United States	26003
46	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
47	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
48	Cross Cancer Institute at University of Alberta	Edmonton	Alberta	Canada	T6G 1Z2

Sponsors and Collaborators

• Radiation Therapy Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: David I. Rosenthal, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00360971
• Other Study ID Numbers: RTOG-0435; CDR0000491088
• First Posted: Aug 7, 2006
• Last Update Posted: Dec 26, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by Radiation Therapy Oncology Group: mucositis; pain; radiation toxicity; stage III squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the hypopharynx; stage III squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the larynx; stage III squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the lip and oral cavity; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx
• Additional relevant MeSH terms: Head and Neck Neoplasms; Mucositis; Stomatitis; Cisplatin

Study Results

Participant Flow

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.	Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
Period Title: Overall Study
STARTED	10	11
COMPLETED	10	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Palifermin	Total
Arm/Group Description	Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.	Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.	Total of all reporting groups
Overall Participants	10	11	21
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52	55	55
Sex: Female, Male (Count of Participants)
Female	0 0%	1 9.1%	1 4.8%
Male	10 100%	10 90.9%	20 95.2%

Outcome Measures

1. Primary Outcome

Title	Duration of Oral Mucositis as Measured in Terms of Days
Description	Duration in days of World Heath Organization (WHO) Grades 3 and 4 oral mucositis during the acute period (defined to be 105 days [15 weeks] or less from the start of treatment); duration is calculated from the onset of a Grade 3 or 4 oral mucositis to the day when an oral mucositis of ≤ Grade 2 is reported after the last oral mucositis of Grade 3 or 4. Patients with grade 0-2 mucositis have a duration of 0. This study required 298 patients to detect via two-sided t-test a reduction of mean duration of at least 9 days from 29 days (standard deviation = 23 days) on the placebo arm with 90% power and alpha = 0.05. Statistical testing was not done due to the small sample size.
Time Frame	Twice-weekly from start of treatment up to 15 weeks after the start of treatment.

Outcome Measure Data

Analysis Population Description

All eligible patients.

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.	Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
Measure Participants	10	11
Mean (Standard Deviation) [Days]	32 (24)	13 (23)

2. Secondary Outcome

Title	Number of Patients With Grade 3 or 4 Mucositis as Measured by the World Heath Organization (WHO) Scale
Description	Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Time Frame	Twice-weekly from start of treatment up to 15 weeks after the start of treatment.

Outcome Measure Data

Analysis Population Description

All randomized patients

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.	Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
Measure Participants	10	11
Count of Participants [Participants]	8 80%	4 36.4%

3. Secondary Outcome

Title	Time to Onset of Grade 3 or 4 Oral Mucositis as Measured by the World Heath Organization (WHO) Scale
Description	Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Time Frame	Twice-weekly from start of treatment up to 15 weeks after the start of treatment.

Outcome Measure Data

Analysis Population Description

All randomized patients

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.	Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
Measure Participants	10	11
Mean (Standard Deviation) [days]	48 (10)	41 (6)

4. Secondary Outcome

Title	Overall Survival
Description	An event is death from any cause. Overall survival was not calculated due to the limited number of events. Number of patients with an event is reported.
Time Frame	From randomization to maximum follow-up at time of analysis of 21 months

Outcome Measure Data

Analysis Population Description

Randomized patients who started protocol treatment

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.	Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
Measure Participants	8	11
Count of Participants [Participants]	2 20%	0 0%

5. Secondary Outcome

Title	Progression-free Survival
Description	An event is defined as the first occurrence of local, regional, distant disease. Progression-free survival is calculated at the time from registration to the death of progression, death in the absence of progression, or last follow-up. Progression-free survival was not calculated due to the limited number of events. Number of patients with an event is reported.
Time Frame	From randomization to maximum follow-up at time of analysis of 21 months

Outcome Measure Data

Analysis Population Description

Randomized patients who started protocol treatment

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.	Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
Measure Participants	8	11
Count of Participants [Participants]	2 20%	0 0%

6. Secondary Outcome

Title	Time to Second Primary Tumor
Description	An event is occurrence of a second primary other than basal cell. Time to second primary tumor was not calculated because there were no events. Number of patients with an event is reported.
Time Frame	From randomization to maximum follow-up at time of analysis of 21 months

Outcome Measure Data

Analysis Population Description

Randomized patients who started protocol treatment

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.	Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
Measure Participants	8	11
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Adverse Event Reporting Description	Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE). Mucositis was collected separately from other AE's using the World Health Organization (WHO) grading criteria.
Arm/Group Title	Placebo		Palifermin
Arm/Group Description	Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.		Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
All Cause Mortality
	Placebo		Palifermin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Palifermin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/10 (80%)		5/11 (45.5%)
Gastrointestinal disorders
Mucositis	8/10 (80%)		4/11 (36.4%)
Dry mouth	1/10 (10%)		0/11 (0%)
Dysphagia	1/10 (10%)		1/11 (9.1%)
Nausea	2/10 (20%)		0/11 (0%)
Vomiting NOS	1/10 (10%)		0/11 (0%)
General disorders
Fatigue	0/10 (0%)		1/11 (9.1%)
Infections and infestations
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Appendix	1/10 (10%)		0/11 (0%)
Investigations
Metabolic/laboratory - Other:	1/10 (10%)		0/11 (0%)
Weight decreased	0/10 (0%)		3/11 (27.3%)
Metabolism and nutrition disorders
Anorexia	2/10 (20%)		0/11 (0%)
Dehydration	3/10 (30%)		2/11 (18.2%)
Hypercalcaemia	1/10 (10%)		0/11 (0%)
Hyperglycaemia NOS	1/10 (10%)		0/11 (0%)
Hypokalemia	1/10 (10%)		0/11 (0%)
Hyponatremia	1/10 (10%)		0/11 (0%)
Musculoskeletal and connective tissue disorders
Bone development abnormal	1/10 (10%)		0/11 (0%)
Renal and urinary disorders
Renal failure NOS	1/10 (10%)		0/11 (0%)
Renal/genitourinary - Other:	1/10 (10%)		0/11 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/10 (10%)		0/11 (0%)
Atelectasis	1/10 (10%)		0/11 (0%)
Pharyngolaryngeal pain	0/10 (0%)		1/11 (9.1%)
Skin and subcutaneous tissue disorders
Alopecia	0/10 (0%)		1/11 (9.1%)
Vascular disorders
Vascular - Other:	1/10 (10%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Palifermin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/10 (90%)		11/11 (100%)
Blood and lymphatic system disorders
Hemoglobin	4/10 (40%)		5/11 (45.5%)
Ear and labyrinth disorders
Hearing impaired	2/10 (20%)		3/11 (27.3%)
Tinnitus	2/10 (20%)		2/11 (18.2%)
Endocrine disorders
Endocrine - Other:	1/10 (10%)		0/11 (0%)
Gastrointestinal disorders
Mucositis	2/10 (20%)		7/11 (63.6%)
Caecitis	1/10 (10%)		0/11 (0%)
Constipation	4/10 (40%)		2/11 (18.2%)
Diarrhoea NOS	2/10 (20%)		0/11 (0%)
Dry mouth	7/10 (70%)		9/11 (81.8%)
Dysphagia	3/10 (30%)		6/11 (54.5%)
Esophageal stenosis acquired	0/10 (0%)		1/11 (9.1%)
Gastrointestinal - Other:	0/10 (0%)		1/11 (9.1%)
Ileal stenosis	0/10 (0%)		1/11 (9.1%)
Nausea	2/10 (20%)		4/11 (36.4%)
Oral pain	2/10 (20%)		2/11 (18.2%)
Oseophagitis NOS	2/10 (20%)		1/11 (9.1%)
Salivary gland disorder NOS	1/10 (10%)		0/11 (0%)
Toothache	1/10 (10%)		0/11 (0%)
Vomiting NOS	1/10 (10%)		3/11 (27.3%)
General disorders
Edema: head and neck:	3/10 (30%)		0/11 (0%)
Fatigue	5/10 (50%)		2/11 (18.2%)
Pyrexia	0/10 (0%)		1/11 (9.1%)
Infections and infestations
Infection - Other:	2/10 (20%)		1/11 (9.1%)
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Mucosa	1/10 (10%)		0/11 (0%)
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Pharynx	1/10 (10%)		0/11 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils: Neck NOS	1/10 (10%)		0/11 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils: Upper aerodigestive NOS	0/10 (0%)		1/11 (9.1%)
Infection with unknown ANC: Oral cavity-gums (gingivitis)	1/10 (10%)		0/11 (0%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	2/10 (20%)		2/11 (18.2%)
Ecchymosis	1/10 (10%)		0/11 (0%)
Radiation recall syndrome	2/10 (20%)		2/11 (18.2%)
Investigations
Alanine aminotransferase increased	3/10 (30%)		3/11 (27.3%)
Aspartate aminotransferase increased	2/10 (20%)		1/11 (9.1%)
Blood bilirubin increased	1/10 (10%)		0/11 (0%)
Blood creatinine increased	2/10 (20%)		2/11 (18.2%)
Coagulopathy	0/10 (0%)		1/11 (9.1%)
Leukopenia NOS	5/10 (50%)		3/11 (27.3%)
Lymphopenia	1/10 (10%)		1/11 (9.1%)
Metabolic/laboratory - Other:	2/10 (20%)		2/11 (18.2%)
Neutrophil count	2/10 (20%)		2/11 (18.2%)
Platelet count decreased	1/10 (10%)		0/11 (0%)
Weight decreased	5/10 (50%)		7/11 (63.6%)
Metabolism and nutrition disorders
Anorexia	4/10 (40%)		4/11 (36.4%)
Dehydration	1/10 (10%)		3/11 (27.3%)
Hyperglycaemia NOS	2/10 (20%)		2/11 (18.2%)
Hyperkalaemia	1/10 (10%)		0/11 (0%)
Hyperuricemia	1/10 (10%)		1/11 (9.1%)
Hypoalbuminemia	1/10 (10%)		0/11 (0%)
Hypocalcemia	1/10 (10%)		0/11 (0%)
Hypokalemia	0/10 (0%)		1/11 (9.1%)
Hypomagnesemia	1/10 (10%)		2/11 (18.2%)
Hyponatremia	1/10 (10%)		2/11 (18.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/10 (0%)		1/11 (9.1%)
Fibrosis-deep connective tissue:	0/10 (0%)		1/11 (9.1%)
Muscle weakness NOS	0/10 (0%)		1/11 (9.1%)
Neck pain	1/10 (10%)		0/11 (0%)
Trismus	1/10 (10%)		0/11 (0%)
Nervous system disorders
Dysgeusia	6/10 (60%)		5/11 (45.5%)
Headache	1/10 (10%)		0/11 (0%)
Laryngeal nerve dysfunction:	0/10 (0%)		1/11 (9.1%)
Memory impairment	1/10 (10%)		0/11 (0%)
Myelitis NOS	1/10 (10%)		0/11 (0%)
Neuralgia NOS	1/10 (10%)		0/11 (0%)
Neurology - Other:	1/10 (10%)		1/11 (9.1%)
Peripheral sensory neuropathy	1/10 (10%)		1/11 (9.1%)
Tremor	1/10 (10%)		0/11 (0%)
Trigeminal nerve disorder NOS	0/10 (0%)		1/11 (9.1%)
Psychiatric disorders
Agitation	1/10 (10%)		0/11 (0%)
Anxiety	0/10 (0%)		2/11 (18.2%)
Confusional state	1/10 (10%)		0/11 (0%)
Depression	1/10 (10%)		0/11 (0%)
Insomnia	1/10 (10%)		0/11 (0%)
Respiratory, thoracic and mediastinal disorders
Aspiration	0/10 (0%)		1/11 (9.1%)
Atelectasis	0/10 (0%)		1/11 (9.1%)
Hiccups	1/10 (10%)		0/11 (0%)
Laryngeal edema	1/10 (10%)		0/11 (0%)
Laryngitis NOS	2/10 (20%)		1/11 (9.1%)
Pharyngolaryngeal pain	2/10 (20%)		3/11 (27.3%)
Pneumonitis NOS	0/10 (0%)		1/11 (9.1%)
Pulmonary hemorrhage	1/10 (10%)		0/11 (0%)
Skin and subcutaneous tissue disorders
Acne NOS	0/10 (0%)		1/11 (9.1%)
Alopecia	3/10 (30%)		1/11 (9.1%)
Dermatitis exfoliative NOS	2/10 (20%)		1/11 (9.1%)
Pruritus	1/10 (10%)		1/11 (9.1%)
Skin hyperpigmentation	1/10 (10%)		0/11 (0%)
Skin hypopigmentation	1/10 (10%)		0/11 (0%)
Vascular disorders
Flushing	0/10 (0%)		1/11 (9.1%)
Thrombosis	0/10 (0%)		1/11 (9.1%)

Limitations/Caveats

This study terminated early with 21 subjects accrued out of 298 planned, therefore no statistical testing was performed. The termination was decided due to positive preliminary results from other palifermin studies.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.