Palifermin in Lessening Oral Mucositis in Patients Undergoing Radiation Therapy and Chemotherapy for Locally Advanced Head and Neck Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00360971
First received: August 3, 2006
Last updated: August 13, 2013
Last verified: August 2013
  Purpose

RATIONALE: Growth factors, such as palifermin, may lessen the severity of mucositis, or mouth sores, in patients receiving radiation therapy and chemotherapy for head and neck cancer. It is not yet known whether palifermin is more effective than a placebo in lessening mucositis in patients receiving radiation therapy and chemotherapy for head and neck cancer.

PURPOSE: This randomized phase III trial is studying palifermin to see how well it works compared to a placebo in lessening oral mucositis in patients undergoing radiation therapy and chemotherapy for locally advanced head and neck cancer.


Condition Intervention Phase
Head and Neck Cancer
Mucositis
Pain
Radiation Toxicity
Biological: palifermin
Drug: cisplatin
Other: placebo
Procedure: conventional surgery
Radiation: 3-dimensional conformal radiation therapy
Radiation: intensity-modulated radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
Official Title: A Randomized, Phase III, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Palifermin (NSC# 740548; IND # 6370) for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer Receiving Radiation Therapy With Concurrent Chemotherapy (Followed by Surgery for Selected Patients)

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Duration of oral mucositis as measured in terms of days [ Time Frame: From the start of treatment to 15 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and time to onset of mucositis as measured by the WHO scale [ Time Frame: From the start of treatment to 15 weeks ] [ Designated as safety issue: No ]
  • Change in symptom burden and pain as measured by MD Anderson Symptom Inventory-Head and Neck and Brief Pain Inventory questionnaires [ Time Frame: From the start of treatment to 15 weeks ] [ Designated as safety issue: No ]
  • Opioid analgesic usage (total dose in morphine equivalents) [ Time Frame: 4 months from the start of treatment until the end of follow-up ] [ Designated as safety issue: No ]
  • Incidence of xerostomia as measured by Common Toxicity Criteria for Adverse Effects (CTCAE v. 3.0 salivary gland changes/saliva xerostomia scale and the dry mouth/salivary gland xerostomia scale vs patient self-reporting [ Time Frame: From the start of treatment to the end of follow-up ] [ Designated as safety issue: No ]
  • Long-term effects of treatment: overall survival, progression-free survival, and incidence of second primaries [ Time Frame: From registration to the date of death or last follow-up for a maximum of 10 years ] [ Designated as safety issue: No ]
    From registration to the date of death or last follow-up for a maximum of 10 years (progression is defined as the first occurence of local, regional or distant disease progression, occurrence of a second primary other than basal cell or death from any cause; second primary tumor is defined as the occurence or a second primary other than basal cell)


Enrollment: 21
Study Start Date: July 2006
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive palifermin IV on days -3, 5, 12, and 19. Patients who continue to have ulcerative lesions after the completion of chemotherapy and radiotherapy receive palifermin IV once weekly beginning on the last day of chemoradiotherapy and continuing for up to 3 weeks.
Biological: palifermin
Given IV
Drug: cisplatin
Given IV
Procedure: conventional surgery
Some patients may undergo surgery.
Radiation: 3-dimensional conformal radiation therapy
Patients may undergo radiation therapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40.
Radiation: intensity-modulated radiation therapy
Patients may receive radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38.
Placebo Comparator: Arm II
Patients receive placebo IV on days -3, 5, 12, and 19. Patients who continue to have ulcerative lesions at the completion of chemotherapy and radiotherapy receive placebo IV once weekly beginning on the last day of chemoradiotherapy and continuing for up to 3 weeks.
Drug: cisplatin
Given IV
Other: placebo
Given IV
Procedure: conventional surgery
Some patients may undergo surgery.
Radiation: 3-dimensional conformal radiation therapy
Patients may undergo radiation therapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40.
Radiation: intensity-modulated radiation therapy
Patients may receive radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38.

Detailed Description:

OBJECTIVES:

Primary

  • Compare the efficacy of palifermin vs placebo, in terms of burden of acute mucositis (defined to be 105 days [15 weeks] or less from the start of treatment), in patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing concurrent radiotherapy and chemotherapy.

Secondary

  • Compare incidence and time to onset of mucositis in patients treated with these regimens.
  • Compare symptom burden by patient-reported outcomes in patients treated with these regimens.
  • Compare experience of pain and opioid analgesic utilization in patients treated with these regimens.
  • Compare incidence of xerostomia in patients treated with these regimens.
  • Correlate long-term effects of these regimens with disease outcome and survival of these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease stage (III vs IVA or IVB), tumor site (oral cavity or oropharynx vs hypopharynx or larynx), and radiotherapy technique used on study (intensity-modulated radiotherapy [IMRT] vs 3-dimensional conformal radiotherapy [3D-CRT]). Patients are randomized to 1 of 2 treatment arms.

All patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 42-46 (7 weeks for 3D-CRT) or days 1-5, 8-12, 15-19, 22-26, 29-33, 36-38, and 42-46 (7 weeks for IMRT). Patients also receive concurrent chemotherapy comprising cisplatin IV over 1-2 hours on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity.

  • Arm I: Patients receive palifermin IV on days -3, 5, 12, and 19. Patients who continue to have ulcerative lesions after the completion of chemotherapy and radiotherapy receive palifermin IV once weekly beginning on the last day of chemoradiotherapy and continuing for up to 3 weeks.
  • Arm II: Patients receive placebo IV on days -3, 5, 12, and 19. Patients who continue to have ulcerative lesions at the completion of chemotherapy and radiotherapy receive placebo IV once weekly beginning on the last day of chemoradiotherapy and continuing for up to 3 weeks.

Patients are reevaluated 8 weeks after completion of chemoradiotherapy. Patients with remaining tumor at that time may undergo a neck dissection and/or surgical resection of the tumor.

Mucositis, pain, and symptom burden are assessed at baseline, during radiotherapy, and post radiotherapy. Xerostomia is assessed at baseline, during radiotherapy, and several times after completion of study therapy.

After completion of study therapy, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 298 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx, meeting all of the following criteria:

    • At least 2 mucosal sites of the oral cavity/oropharynx mucosa that will be irradiated are assessable by visual transoral inspection
    • Tumors of the larynx or hypolarynx are allowed only if it is anticipated that the 2 index sites in the oral cavity/oropharynx mucosa will be irradiated
    • Selected stage III (excluding T1, N1, M0), or IVA or IVB disease
    • No distant metastases or stage IVC disease (any T, any N, M1)
  • No prior squamous cell cancer of the head and neck

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • Absolute neutrophil count ≥ 1,800/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
  • Bilirubin < 1.5 mg/dL
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 times upper limit of normal
  • Creatinine < 1.5 mg/dL
  • Creatinine clearance ≥ 50 mL/min
  • Able to eat at least soft solids and does not require a feeding tube for nutrition or hydration
  • Calcium normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior invasive malignancy (except nonmelanomatous skin cancer) unless disease free for ≥ 3 years
  • No severe, active co-morbidity, including any of the following:

    • Symptomatic and/or uncontrolled cardiac disease (i.e., New York Heart Association class III-IV cardiac disease)
    • Transmural myocardial infarction within the past 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • Seropositive for hepatitis B virus or hepatitis C virus
    • Seropositive for HIV or confirmed AIDS
    • History of pancreatitis
    • Collagen vascular disease, such as scleroderma
  • No prior allergic reaction or known sensitivity to any of the agents administered during study dosing, including E. coli-derived products, such as any of the following:

    • Somatropin (somatren)
    • Filgrastim (G-CSF)
    • Insulin
    • Interferon alfa-2a
    • Neumega® Oprelvekin (interleukin-11)
    • Interferon alfa-2b
    • Pegfilgrastim
    • Interferon beta-1b

PRIOR CONCURRENT THERAPY:

  • No prior systemic chemotherapy for this cancer

    • Prior chemotherapy for a different cancer is allowed
  • No prior radiotherapy to a region that would result in overlap of radiation therapy fields
  • No prior radical or modified neck dissection
  • No prior initial surgical treatment, excluding diagnostic biopsy of the primary site or nodal sampling of neck disease
  • No prior palifermin or other keratinocyte growth factors (i.e., velafermin or repifermin)
  • Concurrent topical anesthetics allowed
  • No concurrent administration of any of the following during radiotherapy:

    • 'Magic' mouthwash, 'Miracle' mouthwash, or other mouthwash solutions containing chlorhexidine, Gelclair®, hydrogen peroxide, or diphenhydramine
    • Pilocarpine hydrochloride
    • Cevimeline hydrochloride
    • Amifostine
    • Benzydamine hydrochloride
    • Interleukin-11
    • Sargramostim (GM-CSF)
    • Epoetin alfa
    • Sucralfate in suspension form

      • Tablets allowed
    • Steroid rinses
    • Povidone-iodine rinses
    • Glutamine as a prophylactic agent for mucositis
    • Other investigational agents
    • Other biologic response modifiers, with the exception of hematopoietic growth factors for the management of anemia or myelosuppression
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00360971

  Show 48 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Study Chair: David I. Rosenthal, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00360971     History of Changes
Other Study ID Numbers: RTOG-0435, CDR0000491088
Study First Received: August 3, 2006
Last Updated: August 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
mucositis
pain
radiation toxicity
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx

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

ClinicalTrials.gov processed this record on April 17, 2014