Radiation Therapy, Carboplatin, and Paclitaxel With or Without Amifostine in Treating Patients With Stage II, Stage III, or Stage IV Head and Neck Cancer

Condition(s) targeted: Cancer-Related Problem/Condition; Head and Neck Cancer

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

Phase: Phase 2

Status: Recruiting

Sponsored by: Dana-Farber Cancer Institute

Official(s) and/or principal investigator(s):
Robert I. Haddad, MD, Study Chair, Affiliation: Dana-Farber Cancer Institute

RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in 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 chemotherapy with radiation therapy may kill more tumor cells. Amifostine may protect normal cells from the side effects of chemotherapy and radiation therapy.

PURPOSE: This randomized phase II trial is studying giving amifostine together with radiation therapy, carboplatin, and paclitaxel to see how well it works compared to radiation therapy, carboplatin, and paclitaxel in treating patients with newly diagnosed stage II, stage III, or stage IV head and neck cancer.

Official title: Phase II, Randomized Study of Concomitant Chemoradiation Using Weekly Carboplatinum/Paclitaxel With (Arm A) or Without (Arm B) Daily Subcutaneous Amifostine in Patients With Newly Diagnosed Locally Advanced Squamous Cell Cancer of the Head and Neck

Study design: Treatment, Randomized, Active Control

Primary outcome:

Rate of local/regional control (LRC) 1 year after beginning treatment

Proportion of patients with grade 2 or 3 chronic xerostomia at 3, 6, and 12 months after completion of study treatment

Proportion of patients with grade 3 and 4 mucositis as assessed by RTOG criteria once weekly during and after completion of radiotherapy

Median duration of dependence on percutaneous endoscopic gastrectomy (PEG) for adequate nutrition at 8, 12, 24, and 52 weeks after completion of study treatment

Secondary outcome:

Duration of grade 3 and 4 mucositis once weekly during treatment and at 8, 12, 24, and 52 weeks after completion of study treatment

Proportion of patients with PEG dependency at 3, 6, and 12 months after completion of study treatment

Time to disease progression

Quality of life as assessed by Functional Assessment of Cancer Therapy for Head and Neck Cancer (FACT-H&N) Survey at baseline and 8, 12, 24, and 52 weeks after completion of study treatment

LRC and overall survival at 2 years after completion of study treatment

Detailed description: OBJECTIVES:

Primary

- Compare the 1-year rate of local and regional disease control in patients with newly

diagnosed stage II, III, or IV squamous cell carcinoma of the head and neck treated with concurrent radiotherapy and chemotherapy comprising carboplatin and paclitaxel with vs without amifostine.

- Compare the 3- and 6-month incidence of grade 2 or 3 chronic xerostomia in patients

treated with these regimens.

- Compare the incidence of grade 3 and 4 mucositis after radiotherapy in patients treated

with these regimens.

- Compare the median duration of dependence on percutaneous endoscopic gastrectomy (PEG)

for adequate nutrition in patients treated with these regimens.

Secondary

- Compare the duration of grade 3 and 4 mucositis in patients treated with these

regimens.

- Compare the 3-, 6-, and 12-month dependence on PEG in patients treated with these

regimens.

- Compare time to disease progression in patients treated with these regimens.

- Compare quality of life of patients treated with these regimens.

- Compare 2-year local and regional disease control in patients treated with these

regimens.

- Compare 2-year survival of patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive carboplatin and paclitaxel once weekly for 6 weeks. Patients

also undergo radiotherapy, concurrently with chemotherapy, once daily for 4 weeks and then twice daily for 2 weeks.

- Arm II: Patients receive chemoradiotherapy as in arm I. Patients also receive amifostine

subcutaneously once daily.

Quality of life is assessed at baseline and then at 8, 12, 24, and 52 weeks after completion of study therapy.

Patients are followed at 8, 12, 24, and 52 weeks.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed squamous cell carcinoma of the head and

neck

- Stage II, III, or IV disease

- No evidence of distant metastases by chest x-ray, abdominal ultrasound, or

CT scan (for patients with liver function abnormalities) or bone scan (for patients with local symptoms)

- Biopsy preferred unless medically contraindicated

- One of the following primary tumor sites:

- Oral cavity

- Oropharynx

- Hypopharynx

- Larynx

- Nasal cavity

- Paranasal cavity

- Unknown primary with metastasis to the head and neck region

- At least 1 uni- or bi-dimensionally measurable lesion

- No prior curative surgery for head and neck cancer

- Biopsy allowed

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- WHO 0-1

Life expectancy

- More than 12 weeks

Hematopoietic

- Neurophil count ≥ 2,000/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 10 g/dL

Hepatic

- Bilirubin normal

- AST and ALT ≤ 2. 5 times upper limit of normal (ULN)*

- Alkaline phosphatase ≤ 5 times ULN* NOTE: *Patients with AST or ALT > 1. 5 times ULN

AND alkaline phosphatase > 2. 5 times ULN are not eligible

Renal

- Creatinine clearance ≥ 60 mL/min

Cardiovascular

- No unstable cardiac disease despite treatment

- No myocardial infarction within the past 6 months

Pulmonary

- No chronic obstructive pulmonary disease requiring hospitalization within the past

year

Other

- No symptomatic peripheral neuropathy ≥ grade 2

- No weight loss > 20% of body weight within the past 3 months (unless purposeful)

- No other malignancy within the past 3 years except adequately treated carcinoma in

situ of the cervix, basal cell or squamous cell skin cancer, or other cancer curatively treated by surgery

- Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior biologic therapy

Chemotherapy

- Prior induction chemotherapy for head and neck cancer allowed before radiotherapy

begins

Endocrine therapy

- Not specified

Radiotherapy

- No prior radiotherapy to the head and neck

Surgery

- See Disease Characteristics

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States; Recruiting
Clinical Trials Office - Beth Israel Deaconess Medical Center, Phone: 617-667-9925

Bethke Cancer Center at Emerson Hospital, Concord, Massachusetts 01742, United States; Recruiting
Clinical Trials Office - Bethke Cancer Center at Emerson Hospi, Phone: 978-287-3460

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Robert I. Haddad, MD, Phone: 617-632-3090

Hudner Oncology Center at Saint Anne's Hospital - Fall River, Fall River, Massachusetts 02721, United States; Recruiting
Clinical Trials Office - Hudner Oncology Center at Saint Anne', Phone: 508-674-5600 ext. 2019

Lowell General Hospital, Lowell, Massachusetts 01854, United States; Recruiting
Blair Ardman, MD, Phone: 978-937-6704

NSMC Cancer Center - Peabody, Peabody, Massachusetts 01960, United States; Recruiting
James F. McIntyre, MD, Phone: 987-977-9400, Email: jfmcintyre@partners.org

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

Starting date: May 2003
Last updated: February 6, 2009