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

This study has been terminated.
(Due to positive preliminary results from other palifermin studies.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00360971
First received: August 3, 2006
Last updated: April 16, 2014
Last verified: April 2014
  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: neck dissection
Radiation: 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: Yes ]

    Duration in days of World Heath Organization (WHO) Grades 3 and 4 oral mucositis during the acute period (defined to be 105 days [15 weeks] or less from the start of treatment); duration is calculated from the onset of a Grade 3 or 4 oral mucositis to the day when an oral mucositis of ≤ Grade 2 is reported after the last oral mucositis of Grade 3 or 4. Patients with grade 0-2 mucositis have a duration of 0.

    This study required 298 patients to detect via two-sided t-test a reduction of mean duration of at least 9 days from 29 days (standard deviation = 23 days) on the placebo arm with 90% power and alpha = 0.05.

    Statistical testing was not done due to the small sample size.



Secondary Outcome Measures:
  • Incidence of Mucositis as Measured by the World Heath Organization (WHO) Scale [ Time Frame: From the start of treatment to 15 weeks ] [ Designated as safety issue: Yes ]
  • Time to Onset of Mucositis as Measured by the World Heath Organization (WHO) Scale [ Time Frame: From the start of treatment to 15 weeks ] [ Designated as safety issue: Yes ]
  • Overall Survival [ Time Frame: From registration to 10 years. ] [ Designated as safety issue: No ]
  • Progression-free Survival [ Time Frame: From registration to 10 years. ] [ Designated as safety issue: No ]
  • Time to Second Primary Tumor [ Time Frame: From registration to 10 years. ] [ Designated as safety issue: No ]
    Second primary tumors other than basal cell will be considered.


Enrollment: 21
Study Start Date: July 2006
Study Completion Date: February 2009
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Palifermin
Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
Biological: palifermin
Four doses of palifermin, 180ųg/kg, administered as an i.v. bolus injection over 30-60 seconds. Starting on day -3 (Friday) prior to radiation therapy / chemotherapy and then once weekly, on days 5, 12, and 19.
Drug: cisplatin
Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.
Procedure: neck dissection
A neck dissection is required for patients with persistent nodal disease, any stage, if a palpable abnormality or worrisome radiographic abnormality persists in the neck 8-9 weeks after completion of therapy. A neck dissection is optional for patients with multiple positive lymph nodes or with lymph nodes exceeding 3 cm in diameter at pre-treatment (N2a, N2b, N3) who achieve a complete clinical and radiographic response in the neck. All patients will be assessed at approximately 8 weeks post-treatment with CT scan or MRI by the same technique used at baseline.
Radiation: radiation therapy
A radiation dose of 70 Gy with at least 66 Gy to at least 2 mucosal sites of the oral cavity/oropharynx mucosa. Radiation therapy can be given with 3D conformal (3D-CRT) or with intensity modulated RT (IMRT) techniques; however, the chosen modality must be used for the entire course of treatment.
Placebo Comparator: Placebo
Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.
Drug: cisplatin
Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.
Other: placebo
Four doses of placebo, 180ųg/kg, administered as an i.v. bolus injection over 30-60 seconds. Starting on day -3 (Friday) prior to radiation therapy / chemotherapy and then once weekly, on days 5, 12, and 19.
Procedure: neck dissection
A neck dissection is required for patients with persistent nodal disease, any stage, if a palpable abnormality or worrisome radiographic abnormality persists in the neck 8-9 weeks after completion of therapy. A neck dissection is optional for patients with multiple positive lymph nodes or with lymph nodes exceeding 3 cm in diameter at pre-treatment (N2a, N2b, N3) who achieve a complete clinical and radiographic response in the neck. All patients will be assessed at approximately 8 weeks post-treatment with CT scan or MRI by the same technique used at baseline.
Radiation: radiation therapy
A radiation dose of 70 Gy with at least 66 Gy to at least 2 mucosal sites of the oral cavity/oropharynx mucosa. Radiation therapy can be given with 3D conformal (3D-CRT) or with intensity modulated RT (IMRT) techniques; however, the chosen modality must be used for the entire course of treatment.

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 Grades 3 or 4 oral mucositis in patients treated with these regimens.
  • Compare overall and progression-free survival and time to second primary in patients treated with these regimens.

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.

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
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: 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
Results First Received: April 16, 2014
Last Updated: April 16, 2014
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
Mucositis
Radiation Injuries
Neoplasms by Site
Neoplasms
Mouth Diseases
Stomatognathic Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Wounds and Injuries
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 28, 2014