Squamous Cell Carcinoma of the Head and Neck
Conditions
Keywords
Fractionated Stereotactic Radiosurgery
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.
Interventions
DRUGCetuximab
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.
DEVICEStereotactic radiosurgery
Fractionated stereotactic radiosurgery, 8.0 Gy per fraction for 5 fractions (total: 40.0 Gy)
Sponsors
David A. Clump, MD, PhD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| Overall Survival (OS) | Up to 2 years | Number of months patients remaining alive after study treatment. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab and Stereotactic Radiosurgery Cetuximab: 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.
Stereotactic radiosurgery: Fractionated stereotactic radiosurgery, 8.0 Gy per fraction for 5 fractions (total: 40.0 Gy) | 48 |
| Total | 48 |
Baseline characteristics
| Characteristic | Cetuximab and Stereotactic Radiosurgery |
|---|---|
| Age, Continuous | 63 years |
| Prior chemotherapy | 65 percentage of participants |
| Prior surgery | 67 percentage of participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 48 Participants |
| Received prior epidermal growth factor receptor (EGFR) | 23 percentage of participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 30 Participants |
| Zubrod performance status Score = 0 | 22 Participants |
| Zubrod performance status Score = 1 | 23 Participants |
| Zubrod performance status Score = 2 | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 42 / 48 |
| other Total, other adverse events | 43 / 48 |
| serious Total, serious adverse events | 3 / 48 |
Outcome results
Primary
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.
Time frame: At 1-year
Population: Patients that received study therapy and were evaluable for response to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab and Stereotactic Radiosurgery | 1-year Distant Progression-free Survival (PFS) | 77 percentage of participants |
Primary
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.
Time frame: At 1-year
Population: Patients that received study therapy and were evaluable for response to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab and Stereotactic Radiosurgery | 1-year Local Progression-free Survival (PFS) | 60 percentage of participants |
Primary
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.
Time frame: At 1-year
Population: Patients that received study therapy and were evaluable for response to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab and Stereotactic Radiosurgery | 1-year Locoregional Progression-free Survival (PFS) | 37 percentage of participants |
Secondary
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.
Time frame: At 1-year
Population: Patients that received study therapy and were evaluable for response to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab and Stereotactic Radiosurgery | 1-year Progression-free Survival (PFS) | 33 percentage of participants |
Secondary
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.
Time frame: Up to 24 months / post therapy
Population: Patients that received study therapy and were evaluable for response and by FDG PET.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cetuximab and Stereotactic Radiosurgery | Changes in Tumor Glucose Metabolism | Complete Response (CR) | 9 Participants |
| Cetuximab and Stereotactic Radiosurgery | Changes in Tumor Glucose Metabolism | Partial Response (PR) | 13 Participants |
| Cetuximab and Stereotactic Radiosurgery | Changes in Tumor Glucose Metabolism | Stable Disease (SD) | 5 Participants |
| Cetuximab and Stereotactic Radiosurgery | Changes in Tumor Glucose Metabolism | Progressive Disease (PD) | 17 Participants |
Secondary
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.
Time frame: Up to 24 months; before and after treatment
Population: At the time of this study, PMISO could not be readily obtained due to its relatively short half-life and unforeseen inability to procure this radioisotope locally. Thus, to prevent delay in treating aggressive cancer, F-MISO scans were not performed.
Secondary
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.
Time frame: Up to 2 years
Population: Patients that received study therapy and were evaluable for response to treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cetuximab and Stereotactic Radiosurgery | Overall Response (OR) | Complete response | 9 Participants |
| Cetuximab and Stereotactic Radiosurgery | Overall Response (OR) | Partial Response | 13 Participants |
| Cetuximab and Stereotactic Radiosurgery | Overall Response (OR) | Stable disease | 5 Participants |
| Cetuximab and Stereotactic Radiosurgery | Overall Response (OR) | Disease progression | 17 Participants |
Secondary
Overall Survival (OS)
Number of months patients remaining alive after study treatment.
Time frame: Up to 2 years
Population: Patients that received study therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab and Stereotactic Radiosurgery | Overall Survival (OS) | 10 months |
Secondary
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.
Time frame: Baseline, 6-8 weeks post-treatment; up to 16 months
Population: Patients that received study therapy and were able to complete Quality of Life assessments, who reported stable or improved quality of life.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab and Stereotactic Radiosurgery | Quality of Life (QoL) | 62 percentage of participants |