Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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This trial examines survival and toxicity in previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN) treated with radiosurgery and cetuximab and to evaluate the acute and late toxicities associated with the above therapy.

Detailed Description
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Squamous cell carcinoma of the head and neck is the sixth most common malignancy worldwide with approximately 500,000 cases worldwide yearly. There were an estimated 39,250 new cases and 11,000 deaths in the United States in 2005 (Jemal 2005, Spitz MR). Despite major improvements in the treatment of SCCHN in recent years which include the introduction of concurrent chemoradiotherapy as an effective primary or postoperative therapy, the five-year survival rate for patients with SCCHN in the United States and other developed countries remains poor as nearly 50-60% of these patients will die as a direct result of recurrent locoregional disease. This study aims to determine the 1-year progression-free survival (PFS) of previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN) treated with radiosurgery and cetuximab and to evaluate the acute and late toxicities associated with the therapy.

Official Title
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Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: Cetuximab
* Device: Stereotactic radiosurgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven recurrent squamous cell carcinoma of the head and neck (SCCHN), who has received prior radiotherapy with or without chemotherapy. New primary is allowed if location is in a previously irradiated field. Biopsy is recommended for each recurrence; but is not mandated per study. This will be at the discretion of the principal investigator. Prior radiation dose of at least 60 Gy. Disease confined to locoregional site and can be encompassed in a stereotactic radiosurgery portal Tumor must be deemed to be inoperable or unresectable either by clinical or radiographic criteria. These criteria include encasement of great vessels, vertebral invasion or undue peri-operative risk. Prior surgery for recurrent or new SCCHN is allowed in previously irradiated patients. A minimum of 4 weeks should elapse between any surgery and treatment on study. However, high risk pathologic features should be present, such as positive margins, positive lymphadenopathy, perineural or angiolymphatic invasion. Measurable disease must be present for assessment of response. Karnofsky performance status > 60 (ECOG 0-2) Prior treatment with an EGFR Inhibitor is allowed if it was a part of prior curative therapy and was completed at least 30 days prior to commencement of study therapy Any number of prior chemotherapy regimens are allowed Measurable disease on imaging studies (MRI, CT, PET-CT or physical exam) Age > 18 Estimated life expectancy > 12 weeks No prior radiation therapy or chemotherapy within 1 month of study enrollment No prior chemotherapy or targeted therapy within the previous 4 weeks ANC > 1000, PLT>75,000, Serum creatinine<2.5 mg/dL, Bilirubin <1.5 x upper limits of normal (ULN) Diabetes must be controlled prior to PET-CT scanning (blood glucose <200 mg/dL) Ability to provide written informed consent Exclusion Criteria: Evidence of distant metastasis on upright chest x-ray (CXR), computed tomography (CT) or other staging studies History of any cancer other than SCCHN (except non-melanoma skin cancer or carcinoma in situ of the cervix) within the last 5 years. Patients in their reproductive age group should use an effective method of birth control. Patients who are breast-feeding, or have a positive pregnancy test will be excluded from the study Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the investigator Concurrent serious infection History of known hypersensitivity to cetuximab or similar agents

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab and stereotactic radiosurgery<br> | Drug: Cetuximab<br>* Cetuximab will be administered for 3 weekly doses commencing one week prior to stereotactic radiosurgery treatment as follows: * Cetuximab 400 mg / m2 day -7 (1 week prior to initiation of radiosurgery) * Cetuximab 250 mg/m2 days 0 and +8 (i.e. during the first and second week of fractionated stereotactic radiosurgery) Cetuximab will be administered at 400 mg/m2 IV over 120 minutes on day -7 (loading dose) and 250 mg/m2 IV on days 0 and 8 during the course of stereotactic radiosurgery.<br>* Other names: Erbitux;Device: Stereotactic radiosurgery<br>* Fractionated stereotactic radiosurgery, 8.0 Gy per fraction for 5 fractions (total: 40.0 Gy)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year Local Progression-free Survival (PFS) | Progression (response as assessed by subjective interpretation of the first PET-CT) per Response Evaluation Criteria in Solid Tumors (RECIST v1.0) was defined as greater than 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum and longest diameter recorded since the baseline measurements or the appearance of 1 or more new lesion(s). If the measurable disease was restricted to a solitary lesion, the protocol specified that neoplastic nature should be confirmed by cytology and histology. | At 1-year | 
| 1-year Locoregional Progression-free Survival (PFS) | Progression (response as assessed by subjective interpretation of the first PET-CT) per Response Evaluation Criteria in Solid Tumors (RECIST v1.0) was defined as greater than 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum and longest diameter recorded since the baseline measurements or the appearance of 1 or more new lesion(s). If the measurable disease was restricted to a solitary lesion, the protocol specified that neoplastic nature should be confirmed by cytology and histology. | At 1-year | 
| 1-year Distant Progression-free Survival (PFS) | Progression (response as assessed by subjective interpretation of the first PET-CT) per Response Evaluation Criteria in Solid Tumors (RECIST v1.0) was defined as greater than 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum and longest diameter recorded since the baseline measurements or the appearance of 1 or more new lesion(s). If the measurable disease was restricted to a solitary lesion, the protocol specified that neoplastic nature should be confirmed by cytology and histology. | At 1-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year Progression-free Survival (PFS) | Progression was defined as greater than 20% increase in the sum of the longest diameters of target lesions, per Response Evaluation Criteria in Solid Tumors (RECIST v1.0), taking as reference the smallest sum and longest diameter recorded since the baseline measurements or the appearance of 1 or more new lesion(s). If the measurable disease was restricted to a solitary lesion, the protocol specified that neoplastic nature should be confirmed by cytology and histology. | At 1-year | 
| Overall Survival (OS) | Number of months patients remaining alive after study treatment. | Up to 2 years | 
| Overall Response (OR) | Response by number and percentage of patients assessed by subjective interpretation of the first PET-CT. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response(CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. | Up to 2 years | 
| Changes in Tumor Glucose Metabolism | Glucose metabolism was assessed by FDG PET. FDG uptake reflects the tissue glucose metabolism and is usually high in high-grade tumors and relatively low in low-grade tumors. | Up to 24 months / post therapy | 
| Changes in Tumor Hypoxia. | Changes in tumor hypoxia (tumor cells deprived of oxygen) as a result of Stereotactic radiosurgery (SRS) through assessment by pre-and post-treatment fluorodeoxyglucose (FDG)- and fluoromisonidazole (FMISO)-PET. | Up to 24 months; before and after treatment | 
| Quality of Life (QoL) | Percentage of patients that reported stable and/or improved of quality of life after SBRT as indicated by a quantitative increase or maintenance in overall score. Quality of Life was assessed by longitudinal collection of the University of Washington Quality of Life Registry (UW-QoL-R) survey data, both pre- and post-SBRT. Patients completed the previously validated UW-QoL-R survey at enrollment and again after SBRT. UW-QoL-R measures patient reported QoL in 12 head and neck-specific and 3 global health domains, using a single Likert-scale question with an assigned score of 0 to 100 with 100 representing normal function. | Baseline, 6-8 weeks post-treatment; up to 16 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fractionated Stereotactic Radiosurgery