Back to resultsSBRT With Cetuximab +/- Docetaxel Followed by Adjuvant Cetuximab +/- Docetaxel in Recurrent, Previously-Irradiated SCCHN
Primary Purpose
Previously-Irradiated, Squamous Cell Carcinoma of the Head and Neck Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
SBRT
Cetuximab
Docetaxel
Sponsored by
About this trial
This is an interventional treatment trial for Previously-Irradiated focused on measuring Stereotactic Body Radiation Therapy (SBRT)
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 50 Gy.
- Disease confined to locoregional site and can be encompassed in a stereotactic body 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.
- Karnofsky performance status > 60 (ECOG 0-1)
- 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
- 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
- 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, docetaxel or similar agents
Sites / Locations
- UPMC Hillman Cancer Center - Radiation Oncology
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
SBRT + Cetuximab + Docetaxel followed by Cetuximab + Docetaxel
SBRT + Cetuximab followed by Cetuximab
Arm Description
Previously Treated With Cetuximab - Group A; No Previous Cetuximab - Group C
Previously Treated with Cetuximab - Group B; No Previous Cetuximab - Group D
Outcomes
Primary Outcome Measures
1-Year Locoregional Progression-free survival (PFS)
The proportion of previously-irradiated patients treated with SBRT, cetuximab, and/or docetaxel, evaluated by PET/CT per RECIST Criteria v1.1 that do not experience locoregional disease progression within one year. Per RECIST, Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).
Incidence of distant disease
The proportion of patients with distant disease evaluated by PET/CT or CT per RECIST Criteria v1.1. Malignant disease that has spread to other organs or to lymph nodes other than those near the primary tumor. Per RECIST, Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).
Acute toxicities
Adverse Events and Serious Adverse Events determined by patient follow up per CTCAE v4.0 criteria.
Late toxicities
Adverse Events and Serious Adverse Events determined by patient follow up per CTCAE v4.0 criteria.
Secondary Outcome Measures
Objective Response Rate (ORR)
Incidence of either a confirmed Complete Response (CR) or Partial Response (PR), per RECIST Criteria v1.1. Per RECIST, CR is defined as the disappearance of all target lesions. To be assigned a status of complete response, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met. PR is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter. To be assigned a status of partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met.
Overall Survival (OS)
Time from the date of randomization to the date of death due to any cause.
University of Washington QOL Assessment Tool (UW-QOL)
The UW-QOL is a patient-reported outcome measure consisting of domains based upon discrete ordinal responses regarding their past 7 days. Scoring is scaled to so that a score of 0 represents the worst possible response, and a score of 100 represents the best possible response. 12 single question domains, these having between 3 and 6 response options that are scaled evenly from 0 (worst) to 100 (best) according to the hierarchy of response. The domains are pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder, taste, saliva, mood and anxiety. Another question asks patients to choose up to three of these domains that have been the most important to them. There are also three global questions, one about how patients feel relative to before they developed their cancer, one about their health-related QOL and one about their overall QOL.
Progression-free Survival (PFS)
Time from the date of entry on study to the date of progression per RECIST Criteria v1.1 or the date of death from any cause. Subjects who are alive and have not progressed will be censored at their last follow-up date. Per RECIST, Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02057107
Brief Title
SBRT With Cetuximab +/- Docetaxel Followed by Adjuvant Cetuximab +/- Docetaxel in Recurrent, Previously-Irradiated SCCHN
Official Title
Randomized Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) With Cetuximab +/- Docetaxel Followed by Adjuvant Cetuximab +/- Docetaxel in Recurrent, Previously-Irradiated Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
July 3, 2013 (Actual)
Primary Completion Date
March 15, 2019 (Actual)
Study Completion Date
December 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Heath Skinner
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The aim of this trial is to examine the addition of docetaxel on disease progression, metastasis and survival of patients otherwise treated with SBRT and cetuximab alone. To better resolve the impact of the experimental treatment the presence/absence of prior cetuximab treatment will be determine before assigning treatment to either cetuximab and SBRT only or cetuximab, SBRT, and docetaxel.
Detailed Description
The aim of this trial is to examine the addition of docetaxel on the overall survival of patients otherwise treated with SBRT and cetuximab alone. In addition, we will determine the difference in progression free survival (PFS), the rate of local recurrence (LR) and of distant metastases (DM) across the SBRT and cetuximab + docetaxel arm and the arm receiving SBRT and cetuximab alone. To better resolve the impact of the experimental treatment on PFS, LR, and DM, patients will be stratified by the presence/absence of prior cetuximab treatment and then randomized to either the control arm (cetuximab and SBRT only) or the experimental arm (cetuximab, SBRT, and docetaxel).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Previously-Irradiated, Squamous Cell Carcinoma of the Head and Neck Cancer
Keywords
Stereotactic Body Radiation Therapy (SBRT)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SBRT + Cetuximab + Docetaxel followed by Cetuximab + Docetaxel
Arm Type
Other
Arm Description
Previously Treated With Cetuximab - Group A; No Previous Cetuximab - Group C
Arm Title
SBRT + Cetuximab followed by Cetuximab
Arm Type
Other
Arm Description
Previously Treated with Cetuximab - Group B; No Previous Cetuximab - Group D
Intervention Type
Radiation
Intervention Name(s)
SBRT
Other Intervention Name(s)
Radiosurgery, Stereotactic radiosurgery, CyberKnife, True Beam, Trilogy
Intervention Description
8.8-10 Gy per fraction (total: 44-50 Gy)
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
Day -7 (One week prior to commencement of stereotactic radiosurgery):
Cetuximab, 400 mg/m2
Days 0 and 8 (The 1st and 2nd week of radiosurgery):
Cetuximab, 250 mg/m2 Cetuximab, 250 mg/m2 will be given weekly ( following radiosurgery)
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
Taxotere
Intervention Description
Days 0 and 8 (The 1st and 2nd week of radiosurgery) Docetaxel, 25 mg/m2 Docetaxel, 25 mg/m2 will be given weekly (following radiosurgery)
Primary Outcome Measure Information:
Title
1-Year Locoregional Progression-free survival (PFS)
Description
The proportion of previously-irradiated patients treated with SBRT, cetuximab, and/or docetaxel, evaluated by PET/CT per RECIST Criteria v1.1 that do not experience locoregional disease progression within one year. Per RECIST, Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).
Time Frame
Up to 12 months
Title
Incidence of distant disease
Description
The proportion of patients with distant disease evaluated by PET/CT or CT per RECIST Criteria v1.1. Malignant disease that has spread to other organs or to lymph nodes other than those near the primary tumor. Per RECIST, Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).
Time Frame
Up to 12 months
Title
Acute toxicities
Description
Adverse Events and Serious Adverse Events determined by patient follow up per CTCAE v4.0 criteria.
Time Frame
Up to 3 months after SBRT treatment
Title
Late toxicities
Description
Adverse Events and Serious Adverse Events determined by patient follow up per CTCAE v4.0 criteria.
Time Frame
From 3 months after SBRT treatment, up to 3 years
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
Incidence of either a confirmed Complete Response (CR) or Partial Response (PR), per RECIST Criteria v1.1. Per RECIST, CR is defined as the disappearance of all target lesions. To be assigned a status of complete response, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met. PR is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter. To be assigned a status of partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met.
Time Frame
Up to 12 months
Title
Overall Survival (OS)
Description
Time from the date of randomization to the date of death due to any cause.
Time Frame
Up to 5 years
Title
University of Washington QOL Assessment Tool (UW-QOL)
Description
The UW-QOL is a patient-reported outcome measure consisting of domains based upon discrete ordinal responses regarding their past 7 days. Scoring is scaled to so that a score of 0 represents the worst possible response, and a score of 100 represents the best possible response. 12 single question domains, these having between 3 and 6 response options that are scaled evenly from 0 (worst) to 100 (best) according to the hierarchy of response. The domains are pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder, taste, saliva, mood and anxiety. Another question asks patients to choose up to three of these domains that have been the most important to them. There are also three global questions, one about how patients feel relative to before they developed their cancer, one about their health-related QOL and one about their overall QOL.
Time Frame
Up to 5 years
Title
Progression-free Survival (PFS)
Description
Time from the date of entry on study to the date of progression per RECIST Criteria v1.1 or the date of death from any cause. Subjects who are alive and have not progressed will be censored at their last follow-up date. Per RECIST, Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).
Time Frame
Up to 5 years
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 50 Gy.
Disease confined to locoregional site and can be encompassed in a stereotactic body 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.
Karnofsky performance status > 60 (ECOG 0-1)
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
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
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, docetaxel or similar agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David A Clump, MD
Organizational Affiliation
UPMC Hillman Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UPMC Hillman Cancer Center - Radiation Oncology
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
SBRT With Cetuximab +/- Docetaxel Followed by Adjuvant Cetuximab +/- Docetaxel in Recurrent, Previously-Irradiated SCCHN
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