Radiation + Cisplatin or Panitumumab in Locally Advanced Stage III or Stage IV Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy in higher doses over a shorter period of time may kill more tumor cells and have fewer side effects. 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. Monoclonal antibodies, such as panitumumab, 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. It is not yet known whether giving standard radiation therapy together with high-dose cisplatin is more effective than giving higher-dose radiation therapy together with panitumumab in treating patients with locally advanced head and neck cancer. PURPOSE: This randomized phase III trial is comparing two radiation therapy regimens to see how well they work when given together with cisplatin or panitumumab in treating patients with locally advanced stage III or stage IV head and neck cancer.

Detailed Description
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OBJECTIVES: Primary To compare the progression-free survival (PFS) of patients with locally advanced squamous cell carcinoma of the head and neck treated with standard fractionation radiotherapy and high-dose cisplatin vs accelerated fractionation radiotherapy and panitumumab. Secondary To compare overall survival of patients treated with these regimens. To compare local and regional PFS of patients treated with these regimens. To compare distant metastasis in patients treated with these regimens. To compare adverse events, including late radiotherapy-related adverse events in patients treated with these regimens. To compare quality of life (QOL) of patients treated with these regimens. To compare swallowing-related QOL of patients treated with these regimens. To compare economic evaluation (cost effectiveness analysis and cost utility), including both healthcare utilization and indirect costs. OUTLINE: This is a multicenter study. Patients are stratified according to T category (T1-3 vs T4), nodal status (N0-1 vs N2 vs N3), radiotherapy delivery modality (intensity-modulated [IMRT] vs 3-D conformal [3D CRT]), anatomic location (hypopharynx vs oral cavity vs oropharynx vs larynx), and participation in the optional swallowing impairment substudy (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo standard fractionation radiotherapy (IMRT or 3D CRT) once daily, 5 days a week, for 7 weeks. Patients receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy. Arm II: Patients undergo accelerated fractionation radiotherapy (IMRT or 3D CRT) once or twice daily, 5 days a week, for 6 weeks. Patients receive panitumumab IV over 30-90 minutes 1 week prior to and on days 15 and 36 of radiotherapy. Treatment in both arms continues in the absence of disease progression or unacceptable toxicity. Quality of life (QOL) (FACT-H&N), swallowing-related QOL (MDADI, SWAL-QOL), swallowing function (FOIS), and economic evaluations (Lost Productivity questionnaire) are assessed periodically during the study. After completion of study treatment, patients are followed periodically for at least 5 years.

Official Title
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A Phase III Study of Standard Fractionation Radiotherapy With Concurrent High-Dose Cisplatin Versus Accelerated Fractionation Radiotherapy With Panitumumab in Patients With Locally Advanced Stage III and IV Squamous Cell Carcinoma of the Head and Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: panitumumab
* Drug: cisplatin
* Radiation: 3-dimensional conformal radiation therapy
* Radiation: accelerated radiation therapy
* Radiation: intensity-modulated radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically and/or cytologically confirmed (primary lesion or regional lymph nodes) squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx Locally advanced disease, defined by any of the following criteria: Any T, N+, M0 T3-4, N0, M0 No current history of unknown primary squamous cell carcinoma of the head and neck, primary nasopharyngeal, paranasal, or salivary gland tumors of the head and neck PATIENT CHARACTERISTICS: ECOG performance status 0-1 Absolute granulocyte count ≥ 1.5 x 10^9/L Platelet count ≥ 100 x 10^9/L Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST or ALT ≤ 3 times ULN Creatinine clearance > 50 mL/min Magnesium > 0.5 mmol/L Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment Must be accessible for treatment and follow-up Able (sufficiently fluent) and willing to complete the quality of life (QOL) and swallowing QOL questionnaires in either English or French Must be assessed by a radiation oncologist and medical oncologist and deemed suitable for study participation No other malignancies within the past 5 years, except adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, or other curatively treated solid tumors No history of allergic or hypersensitivity reactions to any of the study drugs or their excipients No prior or concurrent interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) on baseline CT scan No peripheral neuropathy ≥ grade 2 (CTCAE v3.0) No hearing loss/tinnitus ≥ grade 3 (CTCAE v3.0) No thromboembolic event within the past 12 months despite being treated with anticoagulation drugs Prior thromboembolic event > 12 months allowed provided patient is stable on anticoagulation or on preventative anticoagulation None of the following allowed: Myocardial infarction within the past 12 months Uncontrolled severe congestive heart failure Unstable angina Active cardiomyopathy Unstable ventricular arrhythmia Uncontrolled hypertension Uncontrolled psychiatric disorder Active serious infection Active peptic ulcer disease Any other medical condition that might interfere with protocol therapy delivery PRIOR CONCURRENT THERAPY: No prior surgical treatment except diagnostic biopsy for this disease No prior induction chemotherapy for this disease No prior radiation to the head and neck region that would result in overlap of fields for this study No prior cisplatin or carboplatin chemotherapy No prior targeted anti-EGFR therapy of any kind At least 30 days since any prior investigational agent No concurrent granulocytic growth factors (e.g., filgrastim [G-CSF]) during radiotherapy No concurrent erythropoietic growth factors, pilocarpine, amifostine, other anticancer therapy (e.g., cytotoxic agents, biological response modifiers, immunotherapy, or hormonal therapy), or other investigational drug therapy The following radiological investigations must be done within 8 weeks of randomization: MRI or CT of the head and neck CT chest

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients undergo standard fractionation radiotherapy (IMRT or 3D CRT) once daily, 5 days a week, for 7 weeks. Patients receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy. | Drug: cisplatin<br>* Given IV<br>Radiation: 3-dimensional conformal radiation therapy<br>* Patients undergo radiotherapy<br>Radiation: intensity-modulated radiation therapy<br>* Patients undergo radiotherapy<br>|
| Experimental: Arm II<br>Patients undergo accelerated fractionation radiotherapy (IMRT or 3D CRT) once or twice daily, 5 days a week, for 6 weeks. Patients receive panitumumab IV over 30-90 minutes 1 week prior to and on days 15 and 36 of radiotherapy. | Biological: panitumumab<br>* Given IV<br>Radiation: 3-dimensional conformal radiation therapy<br>* Patients undergo radiotherapy<br>Radiation: accelerated radiation therapy<br>* Patients undergo accelerated fractionation radiotherapy<br>Radiation: intensity-modulated radiation therapy<br>* Patients undergo radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) Rate | The progression event is defined by first event of the following, Local-regional progression or recurrence Distant metastasis Non-protocol RT, chemotherapy, or biologic therapy without documentation of the site of failure Surgery of primary site with tumour present/unknown Neck dissection with tumour present/unknown, > 15 weeks from end of RT Death due to study cancer or from unknown causes or any other reason Number of patients with and without progression event will be reported. | 6.2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival Rate | Overall survival is defined as the time interval between the date of randomization to date of death from any cause (calculated in months). Otherwise, survival is censored at the last date that the patient is known to be alive. Number of death and alive patients will be reported. | 6.2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III verrucous carcinoma of the larynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, stage IV verrucous carcinoma of the larynx, stage IV squamous cell carcinoma of the oropharynx, stage III verrucous carcinoma of the oral cavity, stage III squamous cell carcinoma of the lip and oral cavity, stage IV verrucous carcinoma of the oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity