Back to resultsA Study of Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer Receiving Postoperative Radiotherapy and Concurrent Chemotherapy
Primary Purpose
Mucositis, Head and Neck Cancer
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Placebo
palifermin
Radiotherapy
Cisplatin
Sponsored by
About this trial
This is an interventional supportive care trial for Mucositis focused on measuring palifermin, Clinical Trial, Oncology, Head & Neck
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Palifermin
Arm 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.
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events (AEs)
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.
Ratio of Ki67-positive Cells Before and After Palifermin Treatment
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.
Pharmacokinetics of Palifermin
Due to the small sample size this analysis was not performed.
Secondary Outcome Measures
Number of Participants With Severe Oral Mucositis (OM) (Adapted RTOG/EORTC Grade ≥3)
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.
Patient-Reported Mouth and Throat Soreness Score
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.
Number of Participants With Disease Progression by Week 12
Disease progression was determined by clinical examination and histopathologic examination by the Investigator.
Overall Survival
Deaths during long-term follow up of subject participating in the acute phase of the study receiving placebo or Palifermin.
Full Information
NCT ID
NCT00626639
First Posted
February 21, 2008
Last Updated
May 29, 2017
Sponsor
Swedish Orphan Biovitrum
Collaborators
Amgen
1. Study Identification
Unique Protocol Identification Number
NCT00626639
Brief Title
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
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 Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
July 2005 (undefined)
Primary Completion Date
May 2007 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swedish Orphan Biovitrum
Collaborators
Amgen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Oral Mucositis associated with adjuvant radiation and concurrent chemotherapy in postoperative Head and Neck setting
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucositis, Head and Neck Cancer
Keywords
palifermin, Clinical Trial, Oncology, Head & Neck
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm 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.
Arm Title
Palifermin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered by intravenous (IV) bolus injection
Intervention Type
Drug
Intervention Name(s)
palifermin
Intervention Description
Administered by intravenous (IV) bolus injection
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
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])
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
100 mg/m^2 intravenously (IV) on days 1, 22 and 43.
Primary Outcome Measure Information:
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)
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
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
Secondary Outcome Measure Information:
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).
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).
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
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
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