Paclitaxel and Radiation Therapy Plus Chemoprotection With Amifostine in Treating Patients With Stage III or Stage IV Head and Neck Cancer

Mass General Brigham

Status and phase: Completed; Phase 2; Phase 1

Conditions: Oral Complications; Head and Neck Cancer

Treatments: Drug: paclitaxel; Procedure: conventional surgery; Drug: amifostine trihydrate; Radiation: radiation therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00003193

ALZA-97-024-ii

CDR0000066028

MGH-M7-20

NCI-V98-1384

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Chemoprotective drugs, such as amifostine, may protect normal cells from the side effects of chemotherapy.

PURPOSE: Phase I/II trial to study the effectiveness of paclitaxel and radiation therapy plus chemoprotection with amifostine in treating patients with stage III or stage IV head and neck cancer.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose of paclitaxel with amifostine and radiotherapy in patients with stage III or IV head and neck cancer.
• Determine the toxic effects and complications of this regimen in terms of mucositis reduction in these patients.
• Determine the complete response rate and progression-free survival of patients treated with this regimen.
• Determine whether amifostine modulates the plasma pharmacokinetics of paclitaxel in these patients.

OUTLINE: This is a dose-escalation study of paclitaxel with and without amifostine.

Patients receive paclitaxel IV on days 1, 8, 15, 29, 36, and 43 for a total of 3-6 doses. Patients also undergo radiotherapy twice daily for 6 weeks, except for days when paclitaxel is given.

Cohorts of 2-5 patients receive escalating doses of paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2-3 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD.

After determination of the MTD for paclitaxel, subsequent patients also receive amifostine IV over 15 minutes on days 1, 8, 29, and 36 and radiotherapy on days 2-5 and 30-33. Determination of the MTD for this drug combination is carried out as with paclitaxel alone.

At 4 to 8 weeks after the last treatment of radiotherapy, patients undergo CT scanning to determine response. Patients with residual masses undergo neck dissection. Patients with complete or partial response at the primary site are followed without surgery.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A maximum of 37 patients will be accrued for this study.

Enrollment: 37 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage III or IV squamous cell head and neck cancer

  • T3-4, N0-3, M0

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance Status:

• ECOG 0-2

Life Expectancy:

• Not specified

Hematopoietic:

• WBC at least 2,000/mm^3
• Platelet count at least 50,000/mm^3

Hepatic:

• Bilirubin no greater than 3.0 mg/dL
• SGOT no greater than 3 times upper limit of normal

Renal:

• Creatinine no greater than 3.0 mg/dL

Other:

• Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No concurrent beta-adrenergic blocking agents

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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37 participants in 1 patient group

Paclitaxel, amifostine, RT

Experimental group

Description:

Dose-escalation arm for paclitaxel with amifostine and RT.

Treatment:

Procedure: conventional surgery

Drug: amifostine trihydrate

Radiation: radiation therapy

Drug: paclitaxel