Chemotherapy and Radiation Therapy With or Without Surgery in Treating Patients With Head and Neck Cancer

Phase 3

Completed

Conditions: Head and Neck Cancer

Interventions: Drug: cisplatin
Radiation: Standard fractionation RT
Radiation: Accelerated fractionation radiation therapy
Procedure: Conventional surgery for select patients

Registration Number: NCT00047008

Lead Sponsor: Radiation Therapy Oncology Group

Brief Summary: RATIONALE: Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. Giving radiation therapy in different ways and combining it with chemotherapy before surgery may kill more tumor cells. It is not yet known which radiation therapy regimen combined with chemotherapy with or without surgery is more effective for head and neck cancer.

PURPOSE: Randomized phase III trial to compare two different radiation therapy regimens combined with cisplatin with or without surgery in treating patients who have stage III or stage IV head and neck cancer.

Detailed Description: OBJECTIVES:

Primary

* Compare overall survival of patients with stage III or IV squamous cell carcinoma of the head and neck treated with conventional vs accelerated radiotherapy and concurrent cisplatin with or without surgical resection.

Secondary

* Compare local-regional control of disease and disease-free rates in patients treated with these regimens.

* Compare the acute and late toxicity of these regimens in these patients.

* Compare quality of life, perception of side effects, and performance status of patients treated with these regimens.

* Determine whether epidermal growth factor receptor and cyclo-oxygenase-2 expressions are independent prognostic markers in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor site (larynx vs other), nodal stage (N0 vs N1 or N2a or N2b vs N2c or N3), and Zubrod performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo standard fractionation radiotherapy 5 days a week for 7 weeks. Patients also receive cisplatin IV on days 1, 22, and 43.

* Arm II: Patients undergo accelerated fractionation radiotherapy 5 days a week for 3.5 weeks and then twice a day, 5 days a week, for 2.5 weeks. Patients also receive cisplatin IV on days 1 and 22.

Patients with biopsy-proven relapsed disease more than 3 months after completion of therapy undergo surgical resection of the primary tumor.

Quality of life is assessed at baseline, during one of the last 2 weeks of treatment, at 3 and 12 months, and then annually for 4 years.

Patients are followed at 6-8 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 720 patients (360 per treatment arm) will be accrued for this study within 3 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 743

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard fractionation RT + cisplatin	cisplatin	Standard fractionation radiation therapy with concurrent cisplatin followed by conventional surgery for select patients.
Standard fractionation RT + cisplatin	Standard fractionation RT	Standard fractionation radiation therapy with concurrent cisplatin followed by conventional surgery for select patients.
Standard fractionation RT + cisplatin	Conventional surgery for select patients	Standard fractionation radiation therapy with concurrent cisplatin followed by conventional surgery for select patients.
Accelerated fractionation RT + cisplatin	Accelerated fractionation radiation therapy	Accelerated fractionation radiation therapy by concomitant boost with concurrent cisplatin followed by conventional surgery for select patients.
Accelerated fractionation RT + cisplatin	Conventional surgery for select patients	Accelerated fractionation radiation therapy by concomitant boost with concurrent cisplatin followed by conventional surgery for select patients.
Accelerated fractionation RT + cisplatin	cisplatin	Accelerated fractionation radiation therapy by concomitant boost with concurrent cisplatin followed by conventional surgery for select patients.

Primary Outcome Measures

Name	Time	Method
Overall Survival (Percentage of Participants Alive)	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.	Overall survival time is defined as time from randomization to the date of death (failure) or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.

Secondary Outcome Measures

Name	Time	Method
Local-regional Failure (Percentage of Participants With Local-regional Failure)	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.	Local-regional failure time is defined as time from randomization to persistent disease in the primary tumor or regional nodes (considered an event at day 1), relapse/progression in either of those sites (considered an event at the time of relapse/progression), death (competing event), or last follow-up (censored). Progression is defined as an estimated increase in the size of the tumor of greater than 25% or appearance of new areas of malignant disease. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.
Local-regional Failure (Alternate Definition) [Percentage of Participants With Local-regional Failure]	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.	Local-regional failure time is defined as time from randomization to relapse/progression in the primary tumor or regional nodes (event), death due to study cancer or unknown causes (event), death due to other causes (competing event), distant metastasis (competing event), or last follow-up (censored). Progression is defined as an estimated increase in the size of the tumor of greater than 25% or appearance of new areas of malignant disease. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.
Disease-free Survival (Percentage of Participants Alive Without Disease)	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.	Disease-free survival time is defined as time from randomization to persistent disease in the primary tumor or regional nodes (considered an event at day 1), relapse/progression in either of those sites (considered an event at the time of relapse/progression), distant metastasis (event), second primary tumor (event), death (event), or last follow-up (censored). Progression is defined as an estimated increase in the size of the tumor of greater than 25% or appearance of new areas of malignant disease. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.
Progression-free Survival (Alternate Definition of Disease-free Survival) [Percentage of Participants Alive Without Progression]	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.	Progression-free survival time is defined as time from randomization to relapse/progression in the primary site or regional nodes (event), distant metastasis (event), death (event), or last follow-up (censored). Progression is defined as an estimated increase in the size of the tumor of greater than 25% or appearance of new areas of malignant disease. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.
Percentage of Participants With Toxicity Grade 3 or Higher	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years.	Acute radiation therapy toxicities (within 90 days from start of radiation therapy) and systemic effects at any time were scored using Common Toxicity Criteria (CTC) version 2.0. Late RT toxicities (\> 90 days from start of radiation therapy) were scored by the Radiation Therapy Oncology Group (RTOG)/European Organisation for. Research and Treatment of Cancer (EORTC) criteria. Both criteria grades toxicity severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event/toxicity data.
Performance Status Scale for Head and Neck Cancer (PSS-HN) Normalcy of Diet Score - Area Under the Curve (AUC) at One Year	Baseline (pretreatment), sometime during the last two weeks of treatment, three months from start of treatment, and one year from start of treatment.	The PSS-HN is a clinician-rated evaluation conducted as an unstructured interview format that assesses three functions: Normalcy of Diet (this outcome measure), Public Eating, and Understandability of Speech. Each function is scored from 0 to 100 and analyzed separately. Higher scores indicate better performance status. Treatment effect was analyzed as time-weighted average between baseline (pre-treatment) and one year calculated by use of area under the curve (AUC).
PSS-HN Public Eating Score - AUC at One Year	Baseline (pretreatment), sometime during the last two weeks of treatment, three months from start of treatment, and one year from start of treatment.	The Performance Status Scale for Head and Neck Cancer (PSS-HN) is a clinician-rated evaluation conducted as an unstructured interview format that assesses three functions: Normalcy of Diet , Public Eating (this outcome measure), and Understandability of Speech. Each function is scored from 0 to 100 and analyzed separately. Higher scores indicate better performance status. Treatment effect was analyzed as time-weighted average between baseline (pretreatment) and one year calculated by use of area under the curve (AUC).
PSS-HN Understandability of Speech Score - AUC at One Year	Baseline (pretreatment), sometime during the last two weeks of treatment, three months from start of treatment, and one year from start of treatment.	The Performance Status Scale for Head and Neck Cancer (PSS-HN) is a clinician-rated evaluation conducted as an unstructured interview format that assesses three functions: Normalcy of Diet , Public Eating, and Understandability of Speech (this outcome measure). Each function is scored from 0 to 100 and analyzed separately. Higher scores indicate better performance status. Treatment effect was analyzed as time-weighted average between baseline (pretreatment) and one year calculated by use of area under the curve (AUC).
Head and Neck Radiotherapy Questionnaire (HNRQ) - AUC at One Year	Baseline (pretreatment), sometime during the last two weeks of treatment, three months from start of treatment, and one year from start of treatment.	The HNRQ is a patient-reported questionnaire administrated through a paper format; it measures radiation-related side effects and the overall well-being of head and neck cancer patients in the past week. The overall score is the mean of the 22 questions, with a range of 1 to 7. Higher scores indicate better quality of life. Treatment effect was analyzed as time-weighted average between baseline (pre-treatment) and 1 year calculated by use of area under the curve (AUC).
Correlation of Epidermal Growth Factor Receptor(EGFR) With Outcomes	From randomization to date of death or last follow-up
Correlation of COX-2 With Outcomes	From randomization to date of death or last follow-up

Trial Locations

Locations (195): Comprehensive Cancer Center at University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Mobile Infirmary Medical Center
🇺🇸
Mobile, Alabama, United States
Foundation for Cancer Research and Education
🇺🇸
Phoenix, Arizona, United States
CCOP - Mayo Clinic Scottsdale Oncology Program
🇺🇸
Scottsdale, Arizona, United States
Scottsdale Healthcare - Shea
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Scottsdale, Arizona, United States
Virginia G. Piper Cancer Center at Scottsdale Healthcare - Osborn
🇺🇸
Scottsdale, Arizona, United States
Providence Saint Joseph Medical Center - Burbank
🇺🇸
Burbank, California, United States
Saint Rose Hospital
🇺🇸
Hayward, California, United States
Cancer Care Consultants Medical Associates at Daniel Freeman Memorial Hospital
🇺🇸
Inglewood, California, United States
Valley Memorial Hospital
🇺🇸
Livermore, California, United States
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Comprehensive Cancer Center at University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States