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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier:
NCT00101582
First received: January 12, 2005
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

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).


Condition Intervention Phase
Mucositis
Solid Tumors
Stomatitis
Head and Neck Cancer
Squamous Cell Carcinoma
Drug: Placebo
Drug: palifermin
Drug: cisplatin chemotherapy
Radiation: Radiotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Swedish Orphan Biovitrum:

Primary Outcome Measures:
  • Number of Participants With Severe (Grade 3 or 4) Oral Mucositis [ Time Frame: Up to Week 15 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 15 weeks ] [ Designated as safety issue: No ]
    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 Frame: Up to 15 weeks ] [ Designated as safety issue: No ]

    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) [ Time Frame: Month 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Assessed twice a week for up to 15 weeks. ] [ Designated as safety issue: No ]

    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 [ Time Frame: Up to 15 weeks ] [ Designated as safety issue: No ]

    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 [ Time Frame: During the 7 weeks of chemotherapy treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: During the 7 weeks of radiotherapy ] [ Designated as safety issue: No ]
    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.


Enrollment: 188
Study Start Date: August 2005
Estimated Study Completion Date: February 2015
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: palifermin
Other Names:
  • Kepivance
  • Recombinant Human Keratinocyte Growth Factor (rHuKGF)
Drug: cisplatin chemotherapy
Commercially available cisplatin was administered as an intravenous infusion at a dose of 100 mg/m^2 on Days 1, 22, and 43.
Radiation: Radiotherapy
Radiotherapy was delivered in 200 cGy daily fractions, 5 days a week.
Placebo Comparator: 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.
Drug: Placebo Drug: cisplatin chemotherapy
Commercially available cisplatin was administered as an intravenous infusion at a dose of 100 mg/m^2 on Days 1, 22, and 43.
Radiation: Radiotherapy
Radiotherapy was delivered in 200 cGy daily fractions, 5 days a week.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00101582

Sponsors and Collaborators
Swedish Orphan Biovitrum
Amgen
Investigators
Study Director: MD Amgen
  More Information

No publications provided

Responsible Party: Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier: NCT00101582     History of Changes
Obsolete Identifiers: NCT00963456
Other Study ID Numbers: 20020402
Study First Received: January 12, 2005
Results First Received: January 3, 2014
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Swedish Orphan Biovitrum:
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

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Mucositis
Stomatitis
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Mouth Diseases
Stomatognathic Diseases
Cisplatin
Mitogens
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014