Neoplasms

All Conditions

Symptoms and General Pathology

Mouth and Tooth Diseases

Digestive System Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Carcinoma

Carcinoma, Squamous Cell

Pain

Head and Neck Neoplasms

Stomatitis

Xerostomia

Mucositis

Oral Ulcer

Laryngeal Diseases

Gastroenteritis

Gastrointestinal Diseases

Mouth Diseases

Stomatognathic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

Mitogens

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.

Placebo

palifermin

Commercially available cisplatin was administered as an intravenous infusion at a dose of 100 mg/m\^2 on Days 1, 22, and 43.

cisplatin chemotherapy

Radiotherapy was delivered in 200 cGy daily fractions, 5 days a week.

Radiotherapy

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).

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.

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

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)

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.

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 (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.

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.

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.

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.

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.

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.

Amgen

Swedish Orphan Biovitrum

The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.

Participants received a single intravenous (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.

Palifermin

Total

Age, Continuous

Sex: Female, Male

Caucasian

Black

Hispanic

American Indian/ Alaska Native

Race/Ethnicity, Customized

Data available for 91 and 94 participants in each treatment group respectively.

Weight

Stage III

Stage IV A

Stage IV B

American Joint Committee on Cancer staging system.

Disease Stage

Oral Cavity

Oropharynx

Nasopharynx

Larynx

Hypopharynx

Tumor Site

Hans Olivecrona, MD PhD

Sample size calculations were based on the number of participants needed to detect, with 90% power and 5% type 1 error rate, at least a 25% difference in the incidence of severe OM between the treatment groups. A 25% absolute reduction in the incidence of severe OM from the placebo group was considered by investigators as clinically meaningful in this clinical setting.

Unknown

The Full Analysis Set included all randomized participants.

Number of Participants With Severe (Grade 3 or 4) Oral Mucositis

To protect the overall type 1 error, the Hochberg procedure was used to adjust for multiple statistical testing of the secondary efficacy endpoints.

Duration of Severe (WHO Grade 3 or 4) Oral Mucositis

Time to Onset of Severe (WHO Grade 3 or 4) Oral Mucositis

Number of Participants With Xerostomia at Month 4 (Grade 2 or Higher)

The Patient Reported Outcome-evaluable analysis set included all randomized patients with a valid Baseline assessment for MTS question 3 of the OMWQ-HN and either:

* At least 1 completed assessment each week for MTS up to withdrawal/Week 8, whichever came first, or
* 70% or greater overall compliance for MTS until withdrawal/Week 8.

Patient-Reported Mouth and Throat Soreness Score

Total Dose of Opioid Analgesics Used for Mucositis Within 15 Weeks

Number of Participants With Unplanned Breaks in Cisplatin Chemotherapy Treatment

Number of Participants With Unplanned Breaks in Radiotherapy

Participants received a single intravenous (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. Chemotherapy consisted of 100 mg/m\^2 cisplatin administered by IV infusion on Days 1, 22, and 43.

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. Chemotherapy consisted of 100 mg/m\^2 cisplatin administered by IV infusion on Days 1, 22, and 43.

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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