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

Sponsor:	Dana-Farber Cancer Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00095927

Purpose

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.

Condition	Intervention	Phase
Chemotherapeutic Agent Toxicity Head and Neck Cancer Mucositis Radiation Toxicity Xerostomia	Drug: amifostine trihydrate Drug: carboplatin Drug: paclitaxel Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Head and Neck Cancer

Drug Information available for: Amifostine Paclitaxel Carboplatin

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Rate of local/regional control (LRC) 1 year after beginning treatment [ Designated as safety issue: No ]
Proportion of patients with grade 2 or 3 chronic xerostomia at 3, 6, and 12 months after completion of study treatment [ Designated as safety issue: No ]
Proportion of patients with grade 3 and 4 mucositis as assessed by RTOG criteria once weekly during and after completion of radiotherapy [ Designated as safety issue: No ]
Median duration of dependence on percutaneous endoscopic gastrectomy (PEG) for adequate nutrition at 8, 12, 24, and 52 weeks after completion of study treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:

Duration of grade 3 and 4 mucositis once weekly during treatment and at 8, 12, 24, and 52 weeks after completion of study treatment [ Designated as safety issue: No ]
Proportion of patients with PEG dependency at 3, 6, and 12 months after completion of study treatment [ Designated as safety issue: No ]
Time to disease progression [ Designated as safety issue: No ]
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 [ Designated as safety issue: No ]
LRC and overall survival at 2 years after completion of study treatment [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	May 2003
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Active Comparator 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.	Drug: carboplatin Given IV Drug: paclitaxel Given IV Radiation: radiation therapy Given once daily for 4 weeks and then twice daily for 2 weeks.
Arm II: Experimental Patients receive chemoradiotherapy as in arm I. Patients also receive amifostine subcutaneously once daily.	Drug: amifostine trihydrate Given subcutaneously Drug: carboplatin Given IV Drug: paclitaxel Given IV Radiation: radiation therapy Given once daily for 4 weeks and then twice daily for 2 weeks.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00095927

Locations

United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Bethke Cancer Center at Emerson Hospital
Concord, Massachusetts, United States, 01742
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
NSMC Cancer Center - Peabody
Peabody, Massachusetts, United States, 01960
Lowell General Hospital
Lowell, Massachusetts, United States, 01854
Hudner Oncology Center at Saint Anne's Hospital - Fall River
Fall River, Massachusetts, United States, 02721

Sponsors and Collaborators

Dana-Farber Cancer Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Robert I. Haddad, MD

Dana-Farber Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Haddad R, Sonis S, Posner M, Wirth L, Costello R, Braschayko P, Allen A, Mahadevan A, Flynn J, Burke E, Li Y, Tishler RB. Randomized phase 2 study of concomitant chemoradiotherapy using weekly carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients with locally advanced head and neck cancer. Cancer. 2009 Oct 1;115(19):4514-23.

Responsible Party:	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute ( Robert I. Haddad )
Study ID Numbers:	CDR0000393493, DFCI-03018
Study First Received:	November 9, 2004
Last Updated:	January 8, 2010
ClinicalTrials.gov Identifier:	NCT00095927 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

radiation toxicity
chemotherapeutic agent toxicity
mucositis
xerostomia
stage II squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage II squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
stage II squamous cell carcinoma of the hypopharynx

stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
stage II squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage II squamous cell carcinoma of the paranasal sinus and nasal cavity
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
untreated metastatic squamous neck cancer with occult primary
metastatic squamous neck cancer with occult primary squamous cell carcinoma

Additional relevant MeSH terms:

Mouth Diseases
Radiation-Protective Agents
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms by Site
Therapeutic Uses
Salivary Gland Diseases
Amifostine
Mucositis
Mitosis Modulators
Carboplatin

Antimitotic Agents
Protective Agents
Xerostomia
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Paclitaxel
Head and Neck Neoplasms
Tubulin Modulators
Stomatognathic Diseases
Gastroenteritis
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on February 08, 2010