Clinical trial NCT00025298: Chemotherapy Plus Radiation Therapy With or Without Amifostine in Treating Patients With 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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Drug/Agent Toxicity by Tissue/Organ
Head and Neck Cancer
Oral Complications
Radiation Toxicity
Keywords: stage II nasopharyngeal cancer
stage III nasopharyngeal cancer
stage IV nasopharyngeal cancer
oral complications
drug/agent toxicity by tissue/organ
radiation toxicity
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 5
Sex: ALL
Minimum age (years): 15
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Nantes-Saint Herblain
country: France
facility: CRLCC Nantes - Atlantique
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Cuneo
country: Italy
facility: Ospedale Santa Croce
city: Genoa (Genova)
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: Milano (Milan)
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
city: Naples
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
city: Jerez
country: Spain
facility: Hospital General de Jerez
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Istanbul
country: Turkey
facility: Istanbul University-Institute of Oncology
city: Glasgow
country: United Kingdom
facility: Beatson Oncology Centre
state: Scotland
Study officials:
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
name: Lisa Licitra, MD
role: STUDY_CHAIR
References: