A Randomized Phase III Trial of Concurrent Accelerated Radiation and Cisplatin Versus Concurrent Accelerated Radiation, Cisplatin, and Cetuximab (C225) [Followed by Surgery for Selected Patients] for Stage III and IV Head and Neck Carcinomas
Overview
- Phase
- Phase 3
- Intervention
- cisplatin
- Conditions
- Head and Neck Cancer
- Sponsor
- Radiation Therapy Oncology Group
- Enrollment
- 940
- Locations
- 369
- Primary Endpoint
- Progression-free Survival (PFS) (3-year Rate Reported)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin may also make tumor cells more sensitive to radiation therapy. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without cetuximab in treating head and neck cancer.
PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin in treating patients with stage III or stage IV head and neck cancer.
Detailed Description
OBJECTIVES: Primary * Evaluate whether the addition of cetuximab to a concurrent radiation-cisplatin regimen will improve progression-free survival in patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, or larynx. Secondary * Determine the impact of the addition of cetuximab to a concurrent radiation-cisplatin regimen on overall survival, local-regional control, acute and late toxic effects, quality of life, and health utilities in these patients. * Correlate the expression of epidermal growth factor receptor (EGFR) and its down-stream molecules with outcome in patients participating in this component of the trial. * Correlate pre-treatment positron emission tomography (PET) scan findings with progression-free survival, overall survival, and local-regional control in patients participating in this component of the trial. * Correlate post-treatment PET scan findings with nodal response and nodal relapse in patients participating in this component of the trial. OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to primary site (larynx vs non-larynx), nodal stage (N0 vs N1, N2a, N2b vs N2c, N3), Zubrod performance status (0 vs 1), use of intensity modulated radiotherapy (IMRT) (no vs yes), and pre-treatment PET/CT scan (no vs yes). Patients are randomized to 1 of 2 treatment arms. NOTE: \*A neck dissection is optional for patients with multiple lymph nodes or lymph nodes \> 3 cm in diameter who achieve a complete clinical and radiographic response in the neck. Quality of life is assessed at baseline, once during the last 2 weeks of treatment, at 3 and 12 months from the start of treatment, and then annually for 4 years. After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
RT + cisplatin
Radiation therapy (RT) as accelerated fractionation by concomitant boost (AFX-CB) or intensity-modulated radiation therapy (IMRT) plus cisplatin
Intervention: cisplatin
RT + cisplatin
Radiation therapy (RT) as accelerated fractionation by concomitant boost (AFX-CB) or intensity-modulated radiation therapy (IMRT) plus cisplatin
Intervention: Accelerated Fractionation by Concomitant Boost
RT + cisplatin
Radiation therapy (RT) as accelerated fractionation by concomitant boost (AFX-CB) or intensity-modulated radiation therapy (IMRT) plus cisplatin
Intervention: Intensity-modulated radiation therapy
RT + cisplatin + cetuximab
Radiation therapy (RT) as accelerated fractionation by concomitant boost (AFX-CB) or intensity-modulated radiation therapy (IMRT) plus cisplatin plus cetuximab
Intervention: cetuximab
RT + cisplatin + cetuximab
Radiation therapy (RT) as accelerated fractionation by concomitant boost (AFX-CB) or intensity-modulated radiation therapy (IMRT) plus cisplatin plus cetuximab
Intervention: cisplatin
RT + cisplatin + cetuximab
Radiation therapy (RT) as accelerated fractionation by concomitant boost (AFX-CB) or intensity-modulated radiation therapy (IMRT) plus cisplatin plus cetuximab
Intervention: Accelerated Fractionation by Concomitant Boost
RT + cisplatin + cetuximab
Radiation therapy (RT) as accelerated fractionation by concomitant boost (AFX-CB) or intensity-modulated radiation therapy (IMRT) plus cisplatin plus cetuximab
Intervention: Intensity-modulated radiation therapy
Outcomes
Primary Outcomes
Progression-free Survival (PFS) (3-year Rate Reported)
Time Frame: From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)
Progression-free survival (PFS) is defined as time from randomization to date of local, regional, or distant disease progression, or death from any cause. Patients last known to be alive without progression are censored at the date of last contact. Three-year rates were estimated by the Kaplan-Meier method. Local or regional progression is defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. Distant progression is defined as clear evidence of distant metastases.
Secondary Outcomes
- Overall Survival (OS) (3-year Rate Reported)(From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.))
- Local-regional Failure (LRF) (3-year Rate Reported)(From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.))
- Rate of Mucositis Toxicity ≥ Grade 3(From start of treatment until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.))
- Rate of Other Toxicity ≥ Grade 3 (Not Mucositis)(From start of treatment until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.))
- Rate of Patients Who Tolerated Treatment(From start of treatment to end of treatment (6-7 weeks))
- Rate of Deaths ≤ 30 Days After Discontinuation of Protocol Treatment(From start of treatment to 30 days after the end of treatment)
- Quality of Life as Measured by European Quality of Life Questionnaire (EQ-5D)(3 months and 12 months)
- Quality of Life as Measured by Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-HN) at 12 Months(Baseline and 12 months)
- Quality of Life as Measured by Proportion of Patients With Performance Status Scale for Head and Neck Cancer (PSS-HN) Scores ≤ 50(3 months and 12 months)
- Correlation of Expression of Epidermal Growth Factor Receptor (EGFR) With PFS, OS, and LRF(From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.))
- Correlation of Pre-treatment Positron Emission Tomography (PET)/CT Maximum Standardized Uptake Value (SUVmax) With PFS, OS, and LRF(From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.))
- 2-year Nodal Relapse Rates in Clinical N2-3 Patients by Post-treatment PET/CT Finding and Nodal Response(From randomization to 2 years)