Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Radiation Therapy With or Without Epoetin alfa in Treating Anemic Patients With 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-9903 RTOG-DEV-1008, NCT00004917, RTOG-99-03

Objectives

Primary

1. Determine whether epoetin alfa given during definitive radiotherapy or chemoradiotherapy improves the local-regional control rate in anemic patients with squamous cell carcinoma of the head and neck.

Secondary

1. Determine whether this drug improves survival in this patient population.
2. Identify patterns in first failure in these patients.
3. Determine whether there is a significant increase in hemoglobin level between the baseline value and the value at 28 days after starting epoetin alfa in these patients.
4. Assess the toxicity of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed invasive squamous cell carcinoma of the head and neck, including carcinoma arising from the oral cavity, oropharynx, larynx, and hypopharynx
  • Stage I-IV disease
  • No distant metastases
  • No carcinoma of the nasopharynx, nasal cavity/paranasal sinuses, or salivary glands
  • No carcinoma in situ without an identifiable invasive component



• Plan for radiotherapy in continuous course



• Prior surgical exploration with gross residual disease remaining allowed



• Prior neck dissection with or without biopsy of primary tumor, but no radical surgery for primary tumor, allowed



• Anemia, defined as hemoglobin no greater than 13.5 g/dL for males and no greater than 12.5 g/dL for females (transfusion prior to study allowed)
  • No severe anemia (i.e., hemoglobin less than 9.0 g/dL)
  • No anemia confirmed to be due to causes other than chronic disease (e.g., iron deficiency anemia)



• Not entered on other RTOG head and neck protocols

Prior/Concurrent Therapy:

Biologic therapy:

• At least 4 weeks since other prior cytokine therapy (e.g., filgrastim [G-CSF], interleukins, or interferons)
• No prior epoetin alfa
• No other concurrent cytokine therapy

Chemotherapy:

• No prior chemotherapy
• Concurrent cisplatin, paclitaxel/cisplatin, or paclitaxel/carboplatin for patients with stage III/IV disease is allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to the head and neck

Surgery:

• See Disease Characteristics

Other:

• No concurrent amifostine
• No concurrent transfusion

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics
• Stage III/IV patients receiving concurrent cisplatin:
  • Absolute neutrophil count at least 2,000/mm³
  • Platelet count at least 100,000/mm³

Hepatic:

• Not specified

Renal:

• Stage III/IV patients receiving concurrent cisplatin:
  • Creatinine no greater than 1.5 mg/dL
  • Creatinine clearance at least 50 mL/min

Cardiovascular:

• No malignant or poorly controlled hypertension (e.g., symptomatic hypertension or diastolic blood pressure of 100 mm Hg or greater despite antihypertensive medication)
• No unstable angina or other poorly controlled cardiac disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• If stage III or IV disease is present, willing to come for twice daily radiotherapy for the last 2.5 weeks of therapy
• No active infection requiring IV antibiotics
• No unexplained fever
• No AIDS or other history of congenital or acquired immunodeficiency
• No other malignancies within the past 3 years except carcinoma in situ or nonmelanomatous skin cancer
• No known hypersensitivity to mammalian cell-derived products or to human albumin
• No acute/subacute illness that would make the need for transfusion likely

Expected Enrollment

A total of 372 patients (186 per arm) will be accrued for this study within 3.5 years.

Outline

This is a randomized study. Patients are stratified according to stage (I/II vs III/IV without chemotherapy vs III/IV with chemotherapy), pretreatment hemoglobin level (9.0 to less than 11.5 g/dL vs 11.5 to 13.5 g/dL), and gender. Patients are randomized to one of two treatment arms.

• Arm I: Patients with stage I or II disease undergo radiotherapy once daily for 6-7 weeks. Patients with stage III or IV disease undergo radiotherapy once daily for 3.5 weeks and then twice daily (6 hours apart) for 2.5 weeks for a total of 6 weeks.



• Arm II: Patients undergo radiotherapy as in arm I. Beginning 7-10 days before radiotherapy, patients receive epoetin alfa subcutaneously once weekly until the end of radiotherapy.

Patients with stage III/IV disease may receive concurrent cisplatin IV over 1-2 hours on days 1 and 22 of radiotherapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Machtay M, Pajak TF, Suntharalingam M, et al.: Radiotherapy with or without erythropoietin for anemic patients with head and neck cancer: a randomized trial of the Radiation Therapy Oncology Group (RTOG 99-03). Int J Radiat Oncol Biol Phys 69 (4): 1008-17, 2007.[PUBMED Abstract]

Machtay M, Pajak T, Suntharalingam M, et al.: Definitive radiotherapy +/- erythropoietin for squamous cell carcinoma of the head and neck: preliminary report of RTOG 99-03. [Abstract] Int J Radiat Oncol Biol Phys 60 (Suppl 1): A-5, S132, 2004.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Mitchell Machtay, MD, Protocol chair(Contact information may not be current)		Ph: 215-662-2428 Email: machtay@xrt.upenn.edu

Registry Information
Official Title		A Randomized Phase III Trial to Assess the Effect of Erythropoietin on Local-Regional Control in Anemic Patients Treated with Radiotherapy for Carcinoma of the Head and Neck
Trial Start Date		2000-06-30
Trial Completion Date		2007-11-15
Registered in ClinicalTrials.gov		NCT00004917
Date Submitted to PDQ		2000-01-13
Information Last Verified		2003-09-30
NCI Grant/Contract Number		CA21661