Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Solid Tumors, Stomatitis, Head and Neck Cancer, Mucositis, Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Placebo
* Drug: palifermin
* Drug: cisplatin chemotherapy
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Palifermin<br>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. | Drug: palifermin<br> <br> * Other names: Recombinant Human Keratinocyte Growth Factor (rHuKGF);Drug: cisplatin chemotherapy<br>* Commercially available cisplatin was administered as an intravenous infusion at a dose of 100 mg/m^2 on Days 1, 22, and 43.<br>Radiation: Radiotherapy<br>* Radiotherapy was delivered in 200 cGy daily fractions, 5 days a week.<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br> <br> Drug: cisplatin chemotherapy<br>* Commercially available cisplatin was administered as an intravenous infusion at a dose of 100 mg/m^2 on Days 1, 22, and 43.<br>Radiation: Radiotherapy<br>* Radiotherapy was delivered in 200 cGy daily fractions, 5 days a week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to Week 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 15 weeks | 
| 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. | Up to 15 weeks | 
| 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. | Month 4 | 
| 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. | Assessed twice a week for up to 15 weeks. | 
| 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. | Up to 15 weeks | 
| 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. | During the 7 weeks of chemotherapy treatment | 
| 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. | During the 7 weeks of radiotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mouth Pain, SCCHN, Palifermin, Mucositis, Oral Cavity, Oropharynx, Nasopharynx, Hypopharynx, Larynx, Mouth Sores, Radiation Therapy, Radiotherapy, Radiochemotherapy, Concurrent Chemotherapy, Xerostomia, Stomatitis, Mucosa, KGF, rHuKGF, Keratinocyte Growth Factor, HNC, Head and Neck Cancer, Oral Mucositis