Back to resultsRe-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck
Primary Purpose
Squamous Cell Carcinoma of the Head and Neck
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cetuximab
Stereotactic radiosurgery
Sponsored by
About this trial
This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck focused on measuring Fractionated Stereotactic Radiosurgery
Eligibility Criteria
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
Sites / Locations
- University of Pittsburgh Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cetuximab and stereotactic radiosurgery
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
Overall Survival (OS)
Number of months patients remaining alive after study treatment.
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.
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.
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.
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.
Full Information
NCT ID
NCT01104922
First Posted
April 8, 2010
Last Updated
February 10, 2022
Sponsor
David A. Clump, MD, PhD
1. Study Identification
Unique Protocol Identification Number
NCT01104922
Brief Title
Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck
Official Title
Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
December 26, 2007 (Actual)
Primary Completion Date
May 21, 2014 (Actual)
Study Completion Date
July 26, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
David A. Clump, MD, PhD
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of the Head and Neck
Keywords
Fractionated Stereotactic Radiosurgery
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cetuximab and stereotactic radiosurgery
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Stereotactic radiosurgery
Intervention Description
Fractionated stereotactic radiosurgery, 8.0 Gy per fraction for 5 fractions (total: 40.0 Gy)
Primary Outcome Measure Information:
Title
1-year Local Progression-free Survival (PFS)
Description
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
Title
1-year Locoregional Progression-free Survival (PFS)
Description
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
Title
1-year Distant Progression-free Survival (PFS)
Description
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
Secondary Outcome Measure Information:
Title
1-year Progression-free Survival (PFS)
Description
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
Title
Overall Survival (OS)
Description
Number of months patients remaining alive after study treatment.
Time Frame
Up to 2 years
Title
Overall Response (OR)
Description
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
Title
Changes in Tumor Glucose Metabolism
Description
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
Title
Changes in Tumor Hypoxia.
Description
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
Title
Quality of Life (QoL)
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David A Clump, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
25680594
Citation
Vargo JA, Ferris RL, Ohr J, Clump DA, Davis KS, Duvvuri U, Kim S, Johnson JT, Bauman JE, Gibson MK, Branstetter BF, Heron DE. A prospective phase 2 trial of reirradiation with stereotactic body radiation therapy plus cetuximab in patients with previously irradiated recurrent squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2015 Mar 1;91(3):480-8. doi: 10.1016/j.ijrobp.2014.11.023. Epub 2015 Jan 30.
Results Reference
derived
Learn more about this trial
Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck
We'll reach out to this number within 24 hrs