Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Supportive care, Treatment	Completed	18 and over	NCI	RTOG-0435 RTOG 0435, NCT00360971

Special Category: NCI Web site featured trial

Objectives

Primary

1. 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

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

Entry 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

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

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
• AST or 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

Expected Enrollment

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

Outcomes

Duration of oral mucositis as measured in terms of days

Incidence and time to onset of mucositis as measured by the WHO scale
Change in symptom burden and pain as measured by MD Anderson Symptom Inventory-Head and Neck and Brief Pain Inventory questionnaires
Use of nutritional support via nasogastric or percutaneous endoscopic gastrostomy feeding tubes
Opioid analgesic usage (total dose in morphine equivalents)
Incidence of xerostomia as measured by CTCAE v. 3.0 salivary gland changes/saliva xerostomia scale and the dry mouth/salivary gland xerostomia scale vs patient self-reporting
Long-term effects of treatment: overall survival, progression-free survival, and incidence of second primaries
Long-term safety
Acute short-term safety

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.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

David Rosenthal, MD, Protocol chair		Ph: 713-563-2300; 800-392-1611 Email: dirosenthal@mdanderson.org

Related Information

Featured trial article

Registry Information
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)
Trial Start Date		2006-07-07
Trial Completion Date		2008-05-03
Registered in ClinicalTrials.gov		NCT00360971
Date Submitted to PDQ		2006-06-05
Information Last Verified		2008-10-24
NCI Grant/Contract Number		CA37422

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