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

Phase 2

Completed

Conditions: Squamous Cell Carcinoma of the Head and Neck

Interventions: Drug: Cetuximab
Device: Stereotactic radiosurgery

Registration Number: NCT01104922

Lead Sponsor: David A. Clump, MD, PhD

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cetuximab and stereotactic radiosurgery	Stereotactic radiosurgery	-
Cetuximab and stereotactic radiosurgery	Cetuximab	-

Primary Outcome Measures

Name	Time	Method
1-year Locoregional Progression-free Survival (PFS)	At 1-year	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.
1-year Local Progression-free Survival (PFS)	At 1-year	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.
1-year Distant Progression-free Survival (PFS)	At 1-year	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.

Secondary Outcome Measures

Name	Time	Method
Overall Response (OR)	Up to 2 years	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.
1-year Progression-free Survival (PFS)	At 1-year	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.
Overall Survival (OS)	Up to 2 years	Number of months patients remaining alive after study treatment.
Changes in Tumor Glucose Metabolism	Up to 24 months / post therapy	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.
Changes in Tumor Hypoxia.	Up to 24 months; before and after treatment	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.
Quality of Life (QoL)	Baseline, 6-8 weeks post-treatment; up to 16 months	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.