Radiation Therapy Cisplatin With or Without Fluorouracil Patients With Stage III or Stage IV Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

A Phase III Randomized Trial Comparing Single Agent Cisplatin With the Combination of 5-Fluorouracil and Cisplatin, Concurrent With Radiation Therapy in Stage III and IV Squamous Cell Head and Neck Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00608205
• Other study ID #: CASE3307
• Secondary ID: NCI-2010-01197
• Status: Completed
• Phase: Phase 3
• Start date: January 2008
• Est. completion date: August 2016

Study information

• Verified date: July 2020
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with cisplatin and fluorouracil may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without fluorouracil in treating patients with head and neck cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy and cisplatin to compare how well they work with or without fluorouracil in treating patients with stage III or stage IV head and neck cancer.

Description:

OBJECTIVES:

• To compare the relapse-free survival of patients treated with radiotherapy and cisplatin with vs without fluorouracil.

• To compare the overall survival, local control without surgery, and patterns of failure in patients treated with these regimens.

• To compare the acute and long-term toxicity of these regimens in these patients.

• To compare the quality of life of patients treated with these regimens.

• To prospectively collect biopsy material, mucosal scrapings, and serum in an effort to generate hypotheses for future correlative studies.

OUTLINE: This is a multicenter study. Patients are stratified according to radiotherapy schedule (once daily vs twice daily) and radiotherapy planning (2D vs 3D vs intensity-modulated radiotherapy). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo full-dose radiotherapy once or twice daily 5 days a week for up to 7 weeks and receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy.

• Arm II: Patients undergo radiotherapy as in arm I and receive fluorouracil IV and cisplatin IV continuously on days 1-4 and 22-25 of radiotherapy.

Patients with biopsy-verified residual disease at the primary site or local recurrence after achieving a complete response to chemoradiotherapy may undergo salvage surgery 12 weeks after the completion of chemoradiotherapy.

Patients complete questionnaires periodically to assess late toxicity and quality of life.

After completion of study treatment, patients are followed periodically.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: August 2016
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx

• No histologic diagnosis other than squamous cell carcinoma

• A primary site must be identified

• Must have locoregionally confined stage III (excluding T1-2, N1) or stage IV disease

• No evidence of nodal disease below the clavicles or distant hematogenous metastases (M0)

• No stage IVC disease (stage IVB disease allowed)

• Deemed appropriate for definitive non-operative management with curative intent

• Resectable disease is not required

• No primary cancer of the nasopharynx, paranasal sinus, or salivary gland

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• WBC > 3,500/mm³

• Platelet count > 100,000/mm³

• Serum creatinine < 2.0 mg/dL

• Alkaline phosphatase < 2 times normal

• AST < 2 times normal

• Bilirubin = 2.0 mg/dL

• Serum calcium normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No unstable or uncontrolled angina

• No clinically apparent jaundice

• No active infection

• No history of any other malignancy (except squamous cell or basal cell skin cancer or cervical carcinoma in situ), unless the patient has been continuously disease-free for at least 5 years

• Not a poor compliance risk

• Able to withstand the rigors of intensive treatment

• Available for and compliant with adequate long-term follow-up

PRIOR CONCURRENT THERAPY:

• No prior definitive surgery or radiotherapy for this malignancy

• No prior chemotherapy, immunotherapy, or epidermal growth factor receptor inhibitors for any disease Patients who have had previous definitive surgery, or radiation therapy for this malignancy, and patients who have had any previous chemotherapy, immunotherapy, or EGF receptor inhibition for any disease are ineligible.

Exclusion Criteria Patients with primary cancers of the nasopharynx, paranasal sinus or salivary gland are ineligible.

Patients with unstable or uncontrolled angina, clinically apparent jaundice, or active infection are ineligible.

Patients with a history of any other malignancy (except squamous or basal cell skin cancer or cervical carcinoma in-situ) are ineligible, unless the patient has been continuously disease-free for at least 5 years.

Patients with any histologic diagnosis other than squamous cell carcinoma are ineligible.

Patients who might be a poor-compliance risk are ineligible.

Pregnant or breastfeeding women are ineligible. Women/men of reproductive potential must be willing to practice acceptable methods of birth control to prevent pregnancy.

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• cisplatin
Given IV
• fluorouracil
Given IV

Radiation:
• radiation therapy
Patients undergo full-dose radiotherapy once or twice daily 5 days a week for up to 7 weeks

Locations

Country	Name	City	State
United States	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse Free Survival	Number of patients that are alive without recurrence when recurrence is defined by any subject with new evidence of cancer after achieving a complete response. Complete response is defined by the complete disappearance of all clinically and radiologically detectable tumor..	at 2 yrs from start of study
Secondary	Patterns of Failure	Patients with any new evidence of cancer after achieving a complete response are considered to have recurrent disease. Biopsy verification will be obtained if at all possible and salvage surgery is recommended if possible. Disease recurrence will be characterized as either local, regional(nodal) or distant recurrence. Patients may have more than one kind of recurrence.	2 years from start of study
Secondary	Overall Survival	Number of patients still alive from 2 years from start of study	2 yrs from start of study
Secondary	Number of Patients With a Clinical Response-complete Disappearance of Detectable Tumor	Twelve weeks after completing chemoradiotherapy, a formal evaluation for response will be made, to include a careful evaluation by the head and neck surgeon, medical and radiation oncologists, and, as appropriate, a radiologic and an endoscopic examination. Patients will be considered to have achieved either a clinical complete response (i.e. complete disappearance of all clinically and radiologically detectable tumor) or to have clinical persistent disease.	at 12 weeks after completing chemoradiotherapy
Secondary	Number of Patients With a Pathological(Final)Complete Response	A Pathological, or final response will be assigned to subjects after any salvage surgery is performed for clinical persistent disease, and after planned neck dissection in those achieving a clinical complete response. If no surgery is performed after chemoradiotherapy, the clinical and pathological (final) response will be the same. Patient will be coded as having either a pathologic complete response, or as having pathologic persistent disease. A pathologic complete response will be defined as the total disappearance of all clinically and radiologically detectable tumor.	at 12 weeks after completing chemoradiotherapy and surgery
Secondary	Disease Recurrence	Number of patients with any new evidence of cancer after achieving a complete response (at 12 weeks after completing chemoradiotherapy) are considered to have recurrent disease.	2 years after start of study
Secondary	Number of Patients That Required a Feeding Tube		12 weeks (after treatment)
Secondary	Number of Patients That Required a Feeding Tube		8 months after start of treatment
Secondary	Number of Patients That Required a Feeding Tube		12 months after start of treatment
Secondary	Number of Patients That Required a Feeding Tube		24 months after start of treatment
Secondary	Nausea Level	Quality of life questionnaire asking "I have nausea".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4).; N (number of patients analyzed) is based on number of patients who completed the question.	12 weeks (after treatment)
Secondary	Nausea Level	Quality of life questionnaire asking "I have nausea".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	8 months from start of treatment
Secondary	Nausea Level	Quality of life questionnaire asking "I have nausea".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 months from start of treatment
Secondary	Nausea Level	Quality of life questionnaire asking "I have nausea".	24 months from start of treatment
Secondary	Dry Mouth	Quality of life questionnaire asking "My mouth is dry".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 weeks (after treatment)
Secondary	Dry Mouth	Quality of life questionnaire asking "My mouth is dry".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	8 months from start of treatment
Secondary	Dry Mouth	Quality of life questionnaire asking "My mouth is dry".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 months from start of treatment
Secondary	Dry Mouth	Quality of life questionnaire asking "My mouth is dry".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	24 months from start of treatment
Secondary	Pain	Quality of life questionnaire asking "I have pain in my mouth, throat or neck".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 weeks (after treatment)
Secondary	Pain	Quality of life questionnaire asking "I have pain in my mouth, throat or neck".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	8 months from start of treatment
Secondary	Pain	Quality of life questionnaire asking "I have pain in my mouth, throat or neck".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 months from start of treatment
Secondary	Pain	Quality of life questionnaire asking "I have pain in my mouth, throat or neck".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	24 months from start of treatment
Secondary	Quality of Life	Quality of life questionnaire asking "I am content with the quality of my life right now".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 weeks (after treatment)
Secondary	Quality of Life	Quality of life questionnaire asking "I am content with the quality of my life right now".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	8 months from start of treatment
Secondary	Quality of Life	Quality of life questionnaire asking "I am content with the quality of my life right now".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 months from start of treatment
Secondary	Quality of Life	Quality of life questionnaire asking "I am content with the quality of my life right now".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	24 months from start of treatment
Secondary	Eating	Quality of life questionnaire asking "I am able to eat the foods i like".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 weeks (after treatment)
Secondary	Eating	Quality of life questionnaire asking "I am able to eat the foods i like".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	8 months from start of treatment
Secondary	Eating	Quality of life questionnaire asking "I am able to eat the foods i like".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 months from start of treatment
Secondary	Eating	Quality of life questionnaire asking "I am able to eat the foods i like".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	24 months from start of treatment
Secondary	Swallowing	Quality of life questionnaire asking "I can swallow naturally and easily".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 weeks (after treatment)
Secondary	Swallowing	Quality of life questionnaire asking "I can swallow naturally and easily".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	8 months after start of treatment
Secondary	Swallowing	Quality of life questionnaire asking "I can swallow naturally and easily".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 months after start of treatment
Secondary	Swallowing	Quality of life questionnaire asking "I can swallow naturally and easily".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	24 months after start of treatment
Secondary	Alcohol Consumption	Quality of life questionnaire asking "I drink alcohol (e.g. beer, wine)".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 weeks (after treatment)
Secondary	Alcohol Consumption	Quality of life questionnaire asking "I drink alcohol (e.g. beer, wine)".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	8 months after start of treatment
Secondary	Alcohol Consumption	Quality of life questionnaire asking "I drink alcohol (e.g. beer, wine)".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 months after start of treatment
Secondary	Alcohol Consumption	Quality of life questionnaire asking "I drink alcohol (e.g. beer, wine)".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	24 months after start of treatment
Secondary	Solid Foods	Quality of life questionnaire asking "I can eat solid foods".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 weeks (after treatment)
Secondary	Solid Foods	Quality of life questionnaire asking "I can eat solid foods".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	8 months after start of treatment
Secondary	Solid Foods	Quality of life questionnaire asking "I can eat solid foods".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	12 months after start of treatment
Secondary	Solid Foods	Quality of life questionnaire asking "I can eat solid foods".; The Categories were assigned a number. The categories were: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), Very much (4). The mean was determined from each statement.	24 months after start of treatment