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)
Overview
- Phase
- Phase 3
- Intervention
- palifermin
- Conditions
- Mucositis
- Sponsor
- Swedish Orphan Biovitrum
- Enrollment
- 188
- Primary Endpoint
- Number of Participants With Severe (Grade 3 or 4) Oral Mucositis
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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)
Arms & Interventions
Palifermin
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.
Intervention: palifermin
Palifermin
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.
Intervention: cisplatin chemotherapy
Palifermin
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.
Intervention: Radiotherapy
Placebo
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: Placebo
Placebo
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: cisplatin chemotherapy
Placebo
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: Radiotherapy
Outcomes
Primary Outcomes
Number of Participants With Severe (Grade 3 or 4) Oral Mucositis
Time Frame: Up to Week 15
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 Outcomes
- Total Dose of Opioid Analgesics Used for Mucositis Within 15 Weeks(Up to 15 weeks)
- Time to Onset of Severe (WHO Grade 3 or 4) Oral Mucositis(Up to 15 weeks)
- Patient-Reported Mouth and Throat Soreness Score(Assessed twice a week for up to 15 weeks.)
- Duration of Severe (WHO Grade 3 or 4) Oral Mucositis(Up to 15 weeks)
- Number of Participants With Xerostomia at Month 4 (Grade 2 or Higher)(Month 4)
- Number of Participants With Unplanned Breaks in Cisplatin Chemotherapy Treatment(During the 7 weeks of chemotherapy treatment)
- Number of Participants With Unplanned Breaks in Radiotherapy(During the 7 weeks of radiotherapy)