Back to resultsPalifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer
Primary Purpose
Mucositis, Solid Tumors, Stomatitis
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Placebo
palifermin
cisplatin chemotherapy
Radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Mucositis focused on measuring SCCHN, Palifermin, Mucositis, Oral Cavity, Oropharynx, Nasopharynx, Hypopharynx, Larynx, Mouth Pain, Mouth Sores, Radiation Therapy, Radiotherapy, Radiochemotherapy, Concurrent Chemotherapy, Xerostomia, Stomatitis, Mucosa, KGF, rHuKGF, Keratinocyte Growth Factor, HNC, Head and Neck Cancer, Oral Mucositis
Eligibility Criteria
Key Inclusion Criteria: Histologically documented squamous cell carcinoma involving either the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx Newly diagnosed, locally advanced stage head and neck cancer (unresectable/unresected disease); American Joint Committee on Cancer [AJCC] Stage III, IVA or IVB amenable to radiotherapy with concurrent chemotherapy as the definitive treatment modality At least 50 Gray of radiation treatment to areas of the oral cavity/oropharynx mucosa that can be visualized Concurrent chemotherapy regimen of Cisplatin 100mg/m^2 on days 1, 22, and 43 Eastern Cooperative Oncology Group (ECOG) performance status (PS) less than or equal to 2 Adequate hematologic, renal and hepatic function Negative pregnancy test by serum or urine Signed informed consent Key Exclusion Criteria: - Presence or history of any other primary malignancy (other than curatively treated in situ cervical cancer, or basal cell carcinoma of the skin without evidence of disease for greater than 3 years)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Palifermin
Placebo
Arm Description
Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.
Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.
Outcomes
Primary Outcome Measures
Number of Participants With Severe (Grade 3 or 4) Oral Mucositis
Participants underwent evaluations of oral mucosal (OM) surfaces (mucositis assessments) 2 times weekly throughout radio/chemotherapy, and 2 times weekly thereafter until severe OM returned to grade ≤ 2 or until Week 15. During each evaluation, the following anatomical areas were assessed: upper lip; lower lip; right cheek; left cheek; right ventral & lateral tongue; left ventral & lateral tongue; floor of the mouth; hard palate; soft palate. A trained evaluator documented the findings using the World Health Organization (WHO) oral toxicity scale according to the following: Grade 0 = None; Grade 1 = Soreness, erythema; Grade 2 = Erythema, ulcers, ability to eat solids; Grade 3 = Ulcers, requires liquid diet; Grade 4 = Alimentation not possible.
Secondary Outcome Measures
Duration of Severe (WHO Grade 3 or 4) Oral Mucositis
The duration of severe oral mucositis (OM) was calculated as the number of days from the onset of severe OM (first time a WHO grade 3 or 4 was observed) to the day when severe OM was resolved (first time WHO grade 2 or less was observed after last WHO grade 3 or 4). Durations of 0 days were assigned to those participants who did not experience any WHO grade 3 or 4 during the study.
Time to Onset of Severe (WHO Grade 3 or 4) Oral Mucositis
Time to onset of severe (WHO Grade 3 or 4) oral mucositis (OM) was analyzed using the Kaplan-Meier procedure.
Participants without an assessed event by the end of the acute OM evaluation phase were censored at the date of last assessment for severe OM.
Number of Participants With Xerostomia at Month 4 (Grade 2 or Higher)
The number of participants with grade 2 or higher xerostomia (dryness of the oral mucosa) at the Month 4 visit, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Dry Mouth/Xerostomia scale.
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 Weekly Questionnaire for Head and Neck Cancer [OMWQ-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).
For each participant, an average patient-reported mouth and throat soreness score was calculated by dividing the sum of the MTS scores at each assessment by the total number of assessments.
Total Dose of Opioid Analgesics Used for Mucositis Within 15 Weeks
The total dose of opioid analgesics (mg of intravenous [IV] morphine equivalents) used by all participants.
Participants with at least one reported administration of opioid analgesic (parenteral, peroral or transdermal) were considered to have received opioid analgesics. The total dose of opioid analgesics is the sum of all opioid analgesic administrations that have been converted to morphine equivalents.
Number of Participants With Unplanned Breaks in Cisplatin Chemotherapy Treatment
Cisplatin was administered on Days 1, 22, and 43. An unplanned break in cisplatin refers to a delay of ≥ 5 days from the scheduled Day 22 or Day 43 cisplatin administration or a discontinuation of cisplatin for any reason.
Number of Participants With Unplanned Breaks in Radiotherapy
Participants with a duration of 5 days or more without an administration of radiotherapy or who discontinue radiotherapy prior to completion of planned radiotherapy were considered to have an unplanned break in radiotherapy.
Full Information
NCT ID
NCT00101582
First Posted
January 12, 2005
Last Updated
August 19, 2016
Sponsor
Swedish Orphan Biovitrum
Collaborators
Amgen
1. Study Identification
Unique Protocol Identification Number
NCT00101582
Brief Title
Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer
Official Title
Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Weekly Doses of Palifermin (rHuKGF) for the Reduction of Oral Mucositis in Subjects With Advanced Head and Neck Cancer Receiving Radiotherapy With Concurrent Chemotherapy (RT/CT)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
August 2005 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
August 2016 (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
The purpose of this research study is to test the safety and effectiveness of palifermin to determine if weekly doses can be safely administered to reduce the incidence (occurrence of), duration (length of time) and severity (amount of pain) of oral mucositis (painful sores in the mouth). Mucositis is a common side effect for patients receiving chemotherapy (cancer-killing drug) and radiotherapy (cancer-killing x-rays) for the treatment of head and neck cancer (HNC).
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 dose of palifermin or placebo at 180 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, Solid Tumors, Stomatitis, Head and Neck Cancer, Squamous Cell Carcinoma
Keywords
SCCHN, Palifermin, Mucositis, Oral Cavity, Oropharynx, Nasopharynx, Hypopharynx, Larynx, Mouth Pain, Mouth Sores, Radiation Therapy, Radiotherapy, Radiochemotherapy, Concurrent Chemotherapy, Xerostomia, Stomatitis, Mucosa, KGF, rHuKGF, Keratinocyte Growth Factor, HNC, Head and Neck Cancer, Oral Mucositis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
188 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Palifermin
Arm Type
Experimental
Arm Description
Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
palifermin
Other Intervention Name(s)
Kepivance, Recombinant Human Keratinocyte Growth Factor (rHuKGF)
Intervention Type
Drug
Intervention Name(s)
cisplatin chemotherapy
Intervention Description
Commercially available cisplatin was administered as an intravenous infusion at a dose of 100 mg/m^2 on Days 1, 22, and 43.
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
Radiotherapy was delivered in 200 cGy daily fractions, 5 days a week.
Primary Outcome Measure Information:
Title
Number of Participants With Severe (Grade 3 or 4) Oral Mucositis
Description
Participants underwent evaluations of oral mucosal (OM) surfaces (mucositis assessments) 2 times weekly throughout radio/chemotherapy, and 2 times weekly thereafter until severe OM returned to grade ≤ 2 or until Week 15. During each evaluation, the following anatomical areas were assessed: upper lip; lower lip; right cheek; left cheek; right ventral & lateral tongue; left ventral & lateral tongue; floor of the mouth; hard palate; soft palate. A trained evaluator documented the findings using the World Health Organization (WHO) oral toxicity scale according to the following: Grade 0 = None; Grade 1 = Soreness, erythema; Grade 2 = Erythema, ulcers, ability to eat solids; Grade 3 = Ulcers, requires liquid diet; Grade 4 = Alimentation not possible.
Time Frame
Up to Week 15
Secondary Outcome Measure Information:
Title
Duration of Severe (WHO Grade 3 or 4) Oral Mucositis
Description
The duration of severe oral mucositis (OM) was calculated as the number of days from the onset of severe OM (first time a WHO grade 3 or 4 was observed) to the day when severe OM was resolved (first time WHO grade 2 or less was observed after last WHO grade 3 or 4). Durations of 0 days were assigned to those participants who did not experience any WHO grade 3 or 4 during the study.
Time Frame
Up to 15 weeks
Title
Time to Onset of Severe (WHO Grade 3 or 4) Oral Mucositis
Description
Time to onset of severe (WHO Grade 3 or 4) oral mucositis (OM) was analyzed using the Kaplan-Meier procedure.
Participants without an assessed event by the end of the acute OM evaluation phase were censored at the date of last assessment for severe OM.
Time Frame
Up to 15 weeks
Title
Number of Participants With Xerostomia at Month 4 (Grade 2 or Higher)
Description
The number of participants with grade 2 or higher xerostomia (dryness of the oral mucosa) at the Month 4 visit, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Dry Mouth/Xerostomia scale.
Time Frame
Month 4
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 Weekly Questionnaire for Head and Neck Cancer [OMWQ-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).
For each participant, an average patient-reported mouth and throat soreness score was calculated by dividing the sum of the MTS scores at each assessment by the total number of assessments.
Time Frame
Assessed twice a week for up to 15 weeks.
Title
Total Dose of Opioid Analgesics Used for Mucositis Within 15 Weeks
Description
The total dose of opioid analgesics (mg of intravenous [IV] morphine equivalents) used by all participants.
Participants with at least one reported administration of opioid analgesic (parenteral, peroral or transdermal) were considered to have received opioid analgesics. The total dose of opioid analgesics is the sum of all opioid analgesic administrations that have been converted to morphine equivalents.
Time Frame
Up to 15 weeks
Title
Number of Participants With Unplanned Breaks in Cisplatin Chemotherapy Treatment
Description
Cisplatin was administered on Days 1, 22, and 43. An unplanned break in cisplatin refers to a delay of ≥ 5 days from the scheduled Day 22 or Day 43 cisplatin administration or a discontinuation of cisplatin for any reason.
Time Frame
During the 7 weeks of chemotherapy treatment
Title
Number of Participants With Unplanned Breaks in Radiotherapy
Description
Participants with a duration of 5 days or more without an administration of radiotherapy or who discontinue radiotherapy prior to completion of planned radiotherapy were considered to have an unplanned break in radiotherapy.
Time Frame
During the 7 weeks of radiotherapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Histologically documented squamous cell carcinoma involving either the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx
Newly diagnosed, locally advanced stage head and neck cancer (unresectable/unresected disease); American Joint Committee on Cancer [AJCC] Stage III, IVA or IVB amenable to radiotherapy with concurrent chemotherapy as the definitive treatment modality
At least 50 Gray of radiation treatment to areas of the oral cavity/oropharynx mucosa that can be visualized
Concurrent chemotherapy regimen of Cisplatin 100mg/m^2 on days 1, 22, and 43
Eastern Cooperative Oncology Group (ECOG) performance status (PS) less than or equal to 2
Adequate hematologic, renal and hepatic function
Negative pregnancy test by serum or urine
Signed informed consent
Key Exclusion Criteria:
- Presence or history of any other primary malignancy (other than curatively treated in situ cervical cancer, or basal cell carcinoma of the skin without evidence of disease for greater than 3 years)
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
Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer
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