A Study of Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer Receiving Postoperative Radiotherapy and Concurrent Chemotherapy

• Sponsor: Swedish Orphan Biovitrum (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00626639
• Collaborator: Amgen (Industry)
• Enrollment: 5
• Arms: 2
• Duration (Months): 120

Study Details

Study Description

Brief Summary

Oral Mucositis associated with adjuvant radiation and concurrent chemotherapy in postoperative Head and Neck setting

Condition or Disease	Intervention/Treatment	Phase
Mucositis; Head and Neck Cancer	Drug: Placebo; Drug: palifermin; Radiation: Radiotherapy; Drug: Cisplatin	Phase 1/Phase 2

Detailed Description

This study consisted of 2 phases. The acute oral mucositis (OM) evaluation phase includes the time from randomization to the time of severe OM (WHO Grade 3 or 4) resolution (up to Week 12 or up to Week 15 for participants whose severe OM is not resolved at Week 12). In the acute OM evaluation phase, participants were randomized to receive either a single IV bolus dose of palifermin or placebo at 120 μg/kg, 3 days before the start of radiotherapy, plus 7 once-weekly palifermin or placebo doses at the same dose level during a 7-week radio/chemotherapy course. In the long-term follow up phase, participants are followed until death, withdrawal of consent, or loss to follow-up. The long-term follow up phase is still ongoing.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: A Phase 1/2 Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Weekly Doses of Palifermin (rHuKGF) for the Reduction of Oral Mucositis in Subjects With Locally Advanced Head and Neck Cancer (HNC) Receiving Postoperative Radiotherapy With Concurrent Chemotherapy
• Study Start Date: Jul 1, 2005
• Actual Primary Completion Date: May 1, 2007
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.	Drug: Placebo; Administered by intravenous (IV) bolus injection; Radiation: Radiotherapy; Once daily irradiation of 20 centigray (cGy)/day x 33 fractions for a total target dose of 6600 cGy (conventional radiation therapy using standard fractionation [one fraction per day]); Drug: Cisplatin; 100 mg/m^2 intravenously (IV) on days 1, 22 and 43.
Experimental: Palifermin Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.	Drug: palifermin; Administered by intravenous (IV) bolus injection; Radiation: Radiotherapy; Once daily irradiation of 20 centigray (cGy)/day x 33 fractions for a total target dose of 6600 cGy (conventional radiation therapy using standard fractionation [one fraction per day]); Drug: Cisplatin; 100 mg/m^2 intravenously (IV) on days 1, 22 and 43.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) [Up to Week 12 (or Week 15 for participants with severe OM was not resolved by Week 12)]

   An adverse event is an undesirable medical occurrence (sign, symptom, or diagnosis) or worsening of a pre-existing medical condition occurring after start of study drug up to the end of acute oral mucositis (OM) evaluation phase, whether or not considered to be study drug related. If severe OM was not resolved by Week 12, AEs were documented until resolution of severe OM or Week 15, whichever occurred first. A serious AE is any event that is fatal, life threatening, requires or prolongs hospitalization, is a persistent or significant disability/incapacity or is a congenital anomaly/birth defect. The intensity of AEs was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3 based on the following: 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. A Protocol-specific Limiting Toxicity (PSLT) is any non-hematologic Grade 3 or 4 AE considered related to study drug.

2. Ratio of Ki67-positive Cells Before and After Palifermin Treatment [Day -3 predose and 24 or 48 hours post-dose]

   The effect of palifermin on cell proliferation was to be assayed by staining for the cell cycle proliferation marker Ki67 in buccal mucosal biopsy samples taken prior to the first dose and either 24 or 48 hours after the first dose. Due to the small sample size, this analysis was not performed.

3. Pharmacokinetics of Palifermin [Day -3, predose and at 2, 5, 15, 30, 60, and 90 minutes and 2, 4, 6, 8, 10, 12, 24 and 48 hours after the first dose]

   Due to the small sample size this analysis was not performed.

Secondary Outcome Measures

1. Number of Participants With Severe Oral Mucositis (OM) (Adapted RTOG/EORTC Grade ≥3) [Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12).]

   The adapted RTOG/EORTC mucositis assessment scale as follows: Grade 0 = no change; Grade 1 = mild enanthema, mild pain; Grade 2 = patchy mucositis, moderate edema, moderate pain; Grade 3 = confluent fibrinous mucositis, massive edema, massive pain; Grade 4 = extensive ulceration, confluent necrosis, massive hemorrhage. Due to the small sample size this analysis was not performed.

2. Patient-Reported Mouth and Throat Soreness Score [Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12).]

   The average patient-reported mouth and throat soreness (MTS) score as reported on question 3 of the Oral Mucositis Questionnaire for Head and Neck Cancer [OMQ-HN]): "How much mouth and throat soreness did you experience in the past 24 hours?" Participants answered on a scale from 0 (no soreness) to 4 (extreme soreness). Due to the small sample size this analysis was not performed.

3. Number of Participants With Disease Progression by Week 12 [Up to Week 12]

   Disease progression was determined by clinical examination and histopathologic examination by the Investigator.

4. Overall Survival [During long-term follow-up phase, until December 2015]

   Deaths during long-term follow up of subject participating in the acute phase of the study receiving placebo or Palifermin.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• History of newly diagnosed histologically confirmed squamous cell carcinoma (American Joint Committee on Cancer [AJCC] Stage II, III, IVA, or IVB) involving either the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx, post surgical resection (R0, R1)

• Scheduled to receive adjuvant concurrent chemoradiation treatment within 12 weeks of surgery

• High-risk subject defined by presence of at least one of the following: R1 resection margins; T3 or T4 tumor stage; 3 or more positive lymph node metastases; <3 lymph node metastases with extracapsular extension of the disease

• Radiation treatment field to receive planned dose of at least 50Gy to areas of the oral cavity/oropharynx mucosa that can be visualized

Exclusion Criteria:

• Tumors of the lips, paranasal sinuses, salivary glands, or of unknown primary tumors

• Metastatic disease (M1) / Stage IV C

• Presence or history of any other primary malignancy

• History of pancreatitis

• Prior radiotherapy to the site of disease

• Prior chemotherapy

• Other investigational procedures

• Thirty days or less since receiving an investigational product or device in another clinical trial. Current enrollment in another clinical trial is not permitted unless the sole purpose of the trial is for long-term follow-up/survival data

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Swedish Orphan Biovitrum
• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Swedish Orphan Biovitrum
• ClinicalTrials.gov Identifier: NCT00626639
• Other Study ID Numbers: 20040124; NCT00963378
• First Posted: Feb 29, 2008
• Last Update Posted: Jun 21, 2017
• Last Verified: May 1, 2017

• Keywords provided by Swedish Orphan Biovitrum: palifermin; Clinical Trial; Oncology; Head & Neck
• Additional relevant MeSH terms: Head and Neck Neoplasms; Mucositis; Stomatitis; Cisplatin

Study Results

Participant Flow

Recruitment Details	After recruitment of 5 participants, the study was closed to further enrollment due to administrative changes at the study center (ie, departure of principal investigator) and slow enrollment.

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.
Period Title: Overall Study
STARTED	2	3
COMPLETED	0	1
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Placebo	Palifermin	Total
Arm/Group Description	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.	Total of all reporting groups
Overall Participants	2	3	5
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53.0	52.0	52.0
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	2 100%	3 100%	5 100%
Race/Ethnicity, Customized (participants) [Number]
White or Caucasian	2 100%	3 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	An adverse event is an undesirable medical occurrence (sign, symptom, or diagnosis) or worsening of a pre-existing medical condition occurring after start of study drug up to the end of acute oral mucositis (OM) evaluation phase, whether or not considered to be study drug related. If severe OM was not resolved by Week 12, AEs were documented until resolution of severe OM or Week 15, whichever occurred first. A serious AE is any event that is fatal, life threatening, requires or prolongs hospitalization, is a persistent or significant disability/incapacity or is a congenital anomaly/birth defect. The intensity of AEs was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3 based on the following: 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. A Protocol-specific Limiting Toxicity (PSLT) is any non-hematologic Grade 3 or 4 AE considered related to study drug.
Time Frame	Up to Week 12 (or Week 15 for participants with severe OM was not resolved by Week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.
Measure Participants	2	3
Any adverse event	2 100%	3 100%
Serious adverse event	0 0%	2 66.7%
Severe AE (Grade 3, 4 or 5)	0 0%	2 66.7%
Treatment related adverse event	0 0%	1 33.3%
Treatment related serious AE	0 0%	1 33.3%
Treatment related severe AE (Grade 3, 4 or 5)	0 0%	1 33.3%
Study Discontinuation Due to AE	0 0%	0 0%
Protocol Specific Limiting Toxicity (PSLT)	0 0%	0 0%
Deaths	0 0%	1 33.3%

2. Primary Outcome

Title	Ratio of Ki67-positive Cells Before and After Palifermin Treatment
Description	The effect of palifermin on cell proliferation was to be assayed by staining for the cell cycle proliferation marker Ki67 in buccal mucosal biopsy samples taken prior to the first dose and either 24 or 48 hours after the first dose. Due to the small sample size, this analysis was not performed.
Time Frame	Day -3 predose and 24 or 48 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.
Measure Participants	0	0

3. Primary Outcome

Title	Pharmacokinetics of Palifermin
Description	Due to the small sample size this analysis was not performed.
Time Frame	Day -3, predose and at 2, 5, 15, 30, 60, and 90 minutes and 2, 4, 6, 8, 10, 12, 24 and 48 hours after the first dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.
Measure Participants	0	0

4. Secondary Outcome

Title	Number of Participants With Severe Oral Mucositis (OM) (Adapted RTOG/EORTC Grade ≥3)
Description	The adapted RTOG/EORTC mucositis assessment scale as follows: Grade 0 = no change; Grade 1 = mild enanthema, mild pain; Grade 2 = patchy mucositis, moderate edema, moderate pain; Grade 3 = confluent fibrinous mucositis, massive edema, massive pain; Grade 4 = extensive ulceration, confluent necrosis, massive hemorrhage. Due to the small sample size this analysis was not performed.
Time Frame	Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.
Measure Participants	0	0

5. Secondary Outcome

Title	Patient-Reported Mouth and Throat Soreness Score
Description	The average patient-reported mouth and throat soreness (MTS) score as reported on question 3 of the Oral Mucositis Questionnaire for Head and Neck Cancer [OMQ-HN]): "How much mouth and throat soreness did you experience in the past 24 hours?" Participants answered on a scale from 0 (no soreness) to 4 (extreme soreness). Due to the small sample size this analysis was not performed.
Time Frame	Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.
Measure Participants	0	0

6. Secondary Outcome

Title	Number of Participants With Disease Progression by Week 12
Description	Disease progression was determined by clinical examination and histopathologic examination by the Investigator.
Time Frame	Up to Week 12

Outcome Measure Data

Analysis Population Description

Tumor response data was missing for one participant.

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.
Measure Participants	2	2
Number [participants]	1 50%	0 0%

7. Secondary Outcome

Title	Overall Survival
Description	Deaths during long-term follow up of subject participating in the acute phase of the study receiving placebo or Palifermin.
Time Frame	During long-term follow-up phase, until December 2015

Outcome Measure Data

Analysis Population Description

Subjects who received placebo duringthe acute phase of the study.

Arm/Group Title	Placebo	Palifermin
Arm/Group Description	Subjects who received placebo during the acute phase of the study.	Subjects who received Palifermin during the acute phase of the study.
Measure Participants	2	3
Count of Participants [Participants]	2 100%	2 66.7%

Adverse Events

Time Frame	Up to 15 weeks from first dose of IP
Adverse Event Reporting Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Arm/Group Title	Placebo		Palifermin
Arm/Group Description	Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.		Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.
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	0/2 (0%)		2/3 (66.7%)
Blood and lymphatic system disorders
Leukopenia	0/2 (0%)		1/3 (33.3%)
General disorders
Multi-organ failure	0/2 (0%)		1/3 (33.3%)
Infections and infestations
Peritonitis bacterial	0/2 (0%)		1/3 (33.3%)
Septic shock	0/2 (0%)		1/3 (33.3%)
Staphylococcal sepsis	0/2 (0%)		1/3 (33.3%)
Investigations
Blood creatinine increased	0/2 (0%)		1/3 (33.3%)
C-reactive protein increased	0/2 (0%)		1/3 (33.3%)
Red blood cell count increased	0/2 (0%)		1/3 (33.3%)
White blood cell count increased	0/2 (0%)		1/3 (33.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gum neoplasm malignant stage unspecified	0/2 (0%)		1/3 (33.3%)
Other (Not Including Serious) Adverse Events
	Placebo		Palifermin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	0/2 (0%)		1/3 (33.3%)
Lymphadenitis	0/2 (0%)		1/3 (33.3%)
Gastrointestinal disorders
Ascites	0/2 (0%)		1/3 (33.3%)
Dysphagia	1/2 (50%)		0/3 (0%)
Nausea	2/2 (100%)		2/3 (66.7%)
Oral pain	0/2 (0%)		1/3 (33.3%)
Salivary hypersecretion	0/2 (0%)		1/3 (33.3%)
Vomiting	1/2 (50%)		1/3 (33.3%)
General disorders
Facial pain	0/2 (0%)		1/3 (33.3%)
Fatigue	1/2 (50%)		0/3 (0%)
Pyrexia	0/2 (0%)		1/3 (33.3%)
Infections and infestations
Bacteriuria	1/2 (50%)		0/3 (0%)
Nasopharyngitis	0/2 (0%)		1/3 (33.3%)
Urinary tract infection	0/2 (0%)		1/3 (33.3%)
Investigations
Blood creatinine increased	1/2 (50%)		0/3 (0%)
Body temperature increased	0/2 (0%)		1/3 (33.3%)
Nervous system disorders
Headache	1/2 (50%)		0/3 (0%)
Psychiatric disorders
Insomnia	1/2 (50%)		1/3 (33.3%)
Skin and subcutaneous tissue disorders
Erythema	0/2 (0%)		1/3 (33.3%)
Pruritus	0/2 (0%)		1/3 (33.3%)
Skin discolouration	0/2 (0%)		1/3 (33.3%)
Vascular disorders
Lymphoedema	0/2 (0%)		1/3 (33.3%)

Limitations/Caveats

Pharmacokinetic, pharmacodynamic, safety and efficacy endpoints were not evaluable due to the limited number of subjects enrolled.

More Information

Certain Agreements

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

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits sponsor a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Sponsor may remove confidential information, but authors have final control and approval of publication content. For multi-center studies, investigator agrees not to publish any results before the first multi-center publication.