Chemotherapy Plus Radiation Therapy With or Without Amifostine in Treating Patients With Locally Advanced Cancer of the Nasopharynx

Condition(s) targeted: Drug/Agent Toxicity by Tissue/Organ; Head and Neck Cancer; Oral Complications of Cancer and Cancer Therapy; Radiation Toxicity

Intervention: amifostine trihydrate (Drug); carboplatin (Drug); cisplatin (Drug); paclitaxel (Drug); radiation therapy (Procedure)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: European Organization for Research and Treatment of Cancer

Official(s) and/or principal investigator(s):
Lisa Licitra, MD, Study Chair, Affiliation: Fondazione Istituto Nazionale dei Tumori

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Giving chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy and radiation therapy.

PURPOSE: Randomized phase II trial to compare the effectiveness of paclitaxel and carboplatin followed by cisplatin plus radiation therapy with or without amifostine in treating patients who have locally advanced cancer of the nasopharynx.

Official title: A Feasibility Study Of Primary Chemotherapy Followed By Concomitant Chemoradiation With And Without Amifostine In Patients With Locally Advanced Undifferentiated Nasopharyngeal Cancer (UNPC)

Study design: Treatment, Randomized, Active Control

Detailed description: OBJECTIVES:

- Compare the overall incidence of grade 3 or 4 mucositis in patients with locally

advanced undifferentiated nasopharyngeal cancer treated with paclitaxel and carboplatin followed by cisplatin and radiotherapy with or without amifostine.

- Compare the feasibility and activity of these regimens in these patients.

- Determine the toxicity of paclitaxel and carboplatin in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to WHO performance status (0 vs 1 vs 2), response to induction chemotherapy (complete vs partial vs stable disease vs not evaluable), and participating center.

Patients receive induction chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients with a complete or partial response after 2 courses of induction chemotherapy receive 2 additional courses before randomization. Patients with stable disease after 2 courses of induction chemotherapy or who cannot be evaluated after 1 course proceed directly to randomization. Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive cisplatin IV on days 1, 22, and 43. Patients also undergo

radiotherapy daily 5 days a week for 6. 5 weeks.

- Arm II: Patients receive amifostine subcutaneously daily. Patients receive chemotherapy

and radiotherapy as in arm I.

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

PROJECTED ACCRUAL: A total of 41-93 patients will be accrued for this study.

Minimum age: 15 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed undifferentiated nasopharyngeal cancer (UNPC)

- Locoregionally advanced disease

- T2b, N1 (greater than 3 cm) or N2

- T3, N1 (greater than 3 cm) or N2

- T4, N1 (greater than 3 cm) or N2

- Any T, N3

- No squamous cell histology

- At least 1 unidimensionally measurable target lesion

- At least 20 mm by conventional techniques OR

- At least 10 mm by spiral CT scan

- No evidence of distant metastases

- No signs or symptoms of CNS metastases

PATIENT CHARACTERISTICS:

Age:

- 15 to 70

Performance status:

- WHO 0-2

Life expectancy:

- Not specified

Hematopoietic:

- Absolute neutrophil count at least 2,000/mm^3

- Platelet count at least 150,000/mm^3

- Hemoglobin at least 12 g/dL

Hepatic:

- Bilirubin no greater than 1. 5 times upper limit of normal (ULN)

- AST/ALT no greater than 2. 5 times ULN

Renal:

- Creatinine clearance at least 70 mL/min

- Calcium normal

Cardiovascular:

- No hypotension or hypertension requiring therapy

- No prior myocardial infraction

- No pre-existing uncontrolled cardiac disease

- No signs of cardiac failure

- No rhythm disturbances requiring medication

Other:

- No sensory neuropathy grade 2 or greater unless due to cranial nerve

- No uncontrolled infections

- No sensitivity to aminothiol compounds

- No other malignancy within the past 5 years except adequately controlled carcinoma in

situ of the cervix or basal cell or squamous cell skin cancer

- No psychological, familial, sociological, or geographical condition that would

preclude study

- Fertile patients must use effective contraception during and for 3 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No concurrent immunotherapy

Chemotherapy:

- No prior chemotherapy for UNPC

Endocrine therapy:

- No concurrent hormonal therapy except corticosteroids for antiemetic prophylaxis

Radiotherapy:

- No prior radiotherapy for UNPC

Surgery:

- No prior surgery for UNPC except cervical lymphadenectomy

Other:

- At least 1 month since prior investigational agent

- No other concurrent anticancer drugs

Institut Jules Bordet, Brussels 1000, Belgium

U.Z. Gasthuisberg, Leuven B-3000, Belgium

Universitair Ziekenhuis Antwerpen, Edegem B-2650, Belgium

Centre Antoine Lacassagne, Nice 06189, France

CRLCC Nantes - Atlantique, Nantes-Saint Herblain 44805, France

Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano (Milan) 20133, Italy

Istituto Nazionale per la Ricerca sul Cancro, Genoa (Genova) 16132, Italy

Istituto Nazionale per lo Studio e la Cura dei Tumori, Naples 80131, Italy

Ospedale Santa Croce, Cuneo 12100, Italy

Hospital Universitario 12 de Octubre, Madrid 28041, Spain

Hospital General de Jerez, Jerez 11407, Spain

Istanbul University-Institute of Oncology, Istanbul 34390, Turkey

Beatson Oncology Centre, Glasgow, Scotland G11 6NT, United Kingdom

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: July 2001
Last updated: June 17, 2008