A Study of Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer Receiving Postoperative Radiotherapy and Concurrent Chemotherapy

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier:
NCT00626639
First received: February 21, 2008
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

Oral Mucositis associated with adjuvant radiation and concurrent chemotherapy in postoperative Head and Neck setting


Condition Intervention Phase
Mucositis
Head and Neck Cancer
Drug: Placebo
Drug: palifermin
Radiation: Radiotherapy
Drug: Cisplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Supportive Care
Official Title: A Phase 1/2 Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Weekly Doses of Palifermin (rHuKGF) for the Reduction of Oral Mucositis in Subjects With Locally Advanced Head and Neck Cancer (HNC) Receiving Postoperative Radiotherapy With Concurrent Chemotherapy

Resource links provided by NLM:


Further study details as provided by Swedish Orphan Biovitrum:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs) [ Time Frame: Up to Week 12 (or Week 15 for participants with severe OM was not resolved by Week 12) ] [ Designated as safety issue: No ]
    An adverse event is an undesirable medical occurrence (sign, symptom, or diagnosis) or worsening of a pre-existing medical condition occurring after start of study drug up to the end of acute oral mucositis (OM) evaluation phase, whether or not considered to be study drug related. If severe OM was not resolved by Week 12, AEs were documented until resolution of severe OM or Week 15, whichever occurred first. A serious AE is any event that is fatal, life threatening, requires or prolongs hospitalization, is a persistent or significant disability/incapacity or is a congenital anomaly/birth defect. The intensity of AEs was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3 based on the following: Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 = Life-threatening or disabling AE, Grade 5 = Death related to AE. A Protocol-specific Limiting Toxicity (PSLT) is any non-hematologic Grade 3 or 4 AE considered related to study drug.

  • Ratio of Ki67-positive Cells Before and After Palifermin Treatment [ Time Frame: Day -3 predose and 24 or 48 hours post-dose ] [ Designated as safety issue: No ]
    The effect of palifermin on cell proliferation was to be assayed by staining for the cell cycle proliferation marker Ki67 in buccal mucosal biopsy samples taken prior to the first dose and either 24 or 48 hours after the first dose. Due to the small sample size, this analysis was not performed.

  • Pharmacokinetics of Palifermin [ Time Frame: Day -3, predose and at 2, 5, 15, 30, 60, and 90 minutes and 2, 4, 6, 8, 10, 12, 24 and 48 hours after the first dose ] [ Designated as safety issue: No ]
    Due to the small sample size this analysis was not performed.


Secondary Outcome Measures:
  • Number of Participants With Severe Oral Mucositis (OM) (Adapted RTOG/EORTC Grade ≥3) [ Time Frame: Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12). ] [ Designated as safety issue: No ]

    The adapted RTOG/EORTC mucositis assessment scale as follows: Grade 0 = no change; Grade 1 = mild enanthema, mild pain; Grade 2 = patchy mucositis, moderate edema, moderate pain; Grade 3 = confluent fibrinous mucositis, massive edema, massive pain; Grade 4 = extensive ulceration, confluent necrosis, massive hemorrhage.

    Due to the small sample size this analysis was not performed.


  • Patient-Reported Mouth and Throat Soreness Score [ Time Frame: Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12). ] [ Designated as safety issue: No ]

    The average patient-reported mouth and throat soreness (MTS) score as reported on question 3 of the Oral Mucositis Questionnaire for Head and Neck Cancer [OMQ-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).

    Due to the small sample size this analysis was not performed.


  • Number of Participants With Disease Progression by Week 12 [ Time Frame: Up to Week 12 ] [ Designated as safety issue: No ]
    Disease progression was determined by clinical examination and histopathologic examination by the Investigator.

  • Overall Survival [ Time Frame: During long-term follow-up phase, until December 2015 ] [ Designated as safety issue: Yes ]

Enrollment: 5
Study Start Date: July 2005
Estimated Study Completion Date: December 2015
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.
Drug: Placebo
Administered by intravenous (IV) bolus injection
Radiation: Radiotherapy
Once daily irradiation of 20 centigray (cGy)/day x 33 fractions for a total target dose of 6600 cGy (conventional radiation therapy using standard fractionation [one fraction per day])
Drug: Cisplatin
100 mg/m^2 intravenously (IV) on days 1, 22 and 43.
Experimental: Palifermin
Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43.
Drug: palifermin
Administered by intravenous (IV) bolus injection
Radiation: Radiotherapy
Once daily irradiation of 20 centigray (cGy)/day x 33 fractions for a total target dose of 6600 cGy (conventional radiation therapy using standard fractionation [one fraction per day])
Drug: Cisplatin
100 mg/m^2 intravenously (IV) on days 1, 22 and 43.

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 bolus dose of palifermin or placebo at 120 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

Inclusion Criteria:

  • History of newly diagnosed histologically confirmed squamous cell carcinoma (American Joint Committee on Cancer [AJCC] Stage II, III, IVA, or IVB) involving either the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx, post surgical resection (R0, R1)
  • Scheduled to receive adjuvant concurrent chemoradiation treatment within 12 weeks of surgery
  • High-risk subject defined by presence of at least one of the following: R1 resection margins; T3 or T4 tumor stage; 3 or more positive lymph node metastases; <3 lymph node metastases with extracapsular extension of the disease
  • Radiation treatment field to receive planned dose of at least 50Gy to areas of the oral cavity/oropharynx mucosa that can be visualized

Exclusion Criteria:

  • Tumors of the lips, paranasal sinuses, salivary glands, or of unknown primary tumors
  • Metastatic disease (M1) / Stage IV C
  • Presence or history of any other primary malignancy
  • History of pancreatitis
  • Prior radiotherapy to the site of disease
  • Prior chemotherapy
  • Other investigational procedures
  • Thirty days or less since receiving an investigational product or device in another clinical trial. Current enrollment in another clinical trial is not permitted unless the sole purpose of the trial is for long-term follow-up/survival data
  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: NCT00626639

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: NCT00626639     History of Changes
Obsolete Identifiers: NCT00963378
Other Study ID Numbers: 20040124
Study First Received: February 21, 2008
Results First Received: January 24, 2014
Last Updated: January 24, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Keywords provided by Swedish Orphan Biovitrum:
palifermin
Clinical Trial
Oncology
Head & Neck

Additional relevant MeSH terms:
Head and Neck Neoplasms
Mucositis
Stomatitis
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Mouth Diseases
Neoplasms
Neoplasms by Site
Stomatognathic Diseases
Cisplatin
Antineoplastic Agents
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014