Back to resultsStudy of Radiation (RT) Concurrent With Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma (SCC)
Primary Purpose
Head and Neck Cancer
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cetuximab
50-60 Gy and 70 Gy
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Cancer focused on measuring SCC Head and Neck Cancer
Eligibility Criteria
Inclusion Criteria:
- Patients must have pathologically-confirmed, previously untreated, clinically accessible (without general anesthesia) locally advanced squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or nonresectable head and neck squamous cell carcinomas of the skin.
Patients will be limited to:
- ≥ 70 years of age, OR
- with co-morbidities that preclude treatment with standard platinum-based chemotherapy, as determined by the treating physician, OR
- KPS ≤ 80, OR
- Creatinine clearance < 30 cc/min
Laboratory criteria:
- WBC > 3500/ul
- Granulocyte > 1500/ul
- Platelet count > 100,000/ul
- Total Bilirubin < 1.5 X ULN
- AST and ALT < 2.5 X ULN
- Patients must give documented informed consent to participate in this study.
Exclusion Criteria:
- Prior head and neck malignancy, or history of other prior non-head and neck malignancy within the past 3 years (excluding skin cancer and early stage treated prostate cancer).
- Prior head and neck radiation or chemotherapy.
- Documented evidence of distant metastases.
- Patients with nasopharyngeal carcinoma.
- Any medical or psychiatric illness, which, in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment.
- Patients with psychiatric/social situations that would limit compliance with study requirements are not eligible.
- Patients with prior anti-epidermal growth-factor receptor antibody therapy (antibody or small molecule).
- Patients residing in prison.
Sites / Locations
- University of Michigan Medical Center
- University of Michigan Veterans Administration Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment
Arm Description
Outcomes
Primary Outcome Measures
Mean Change in Tumor Epidermal Growth Factor Receptor (EGFR)
The ratio (fold change) of tumor EGFR post-loading dose/pre-loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample.
Mean Change in Tumor Phosphorylated EGFR (pEGFR)
The ratio (fold change) of tumor pEGFR post-loading dose/pre-loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample.
Progression Free Survival Rate
Percentage of participants who survived without recurrent disease, from the time of enrollment to 1 and 2 years.
Overall Survival Rate
Percentage of participants alive at 1 and 2 years after enrollment.
Number of Participants With Treatment Related Toxicities
Toxicities are measured by number of participants who experience one or more types or indicator of toxicity, shown as all grades and grades 3-4. As each participant could have multiple toxicities, the total number of incidents outnumbers the number of participants. Toxicities are graded according to the CTCAE v4.
Secondary Outcome Measures
Change in Tumor EGFR Level Relative to EGFR in Normal Mucosa
Normal mucosa EGFR was assessed for comparison with EGFR in tumor sample. The fold change in tumor EGFR level at post-loading dose/pre-loading dose of cetuximab, relative to fold change in normal mucosa EGFR level post-loading dose/pre-loading dose of cetuximab was summarized across all participants who had an evaluable tumor sample and normal mucosa sample. The value reported is the ratio of fold change in tumor/fold change in buccal EGFR.
Change in Tumor pEGFR Level Relative to pEGFR in Normal Mucosa
Normal mucosa pEGFR was assessed for comparison with pEGFR in tumor sample. The fold change in tumor pEGFR level post-loading dose/pre loading dose of cetuximab, relative to fold change in normal mucosa pEGFR level post-loading dose/pre-loading dose of cetuximab was summarized across all participants who had an evaluable tumor sample and normal mucosa sample. The value reported is the ratio of fold change in tumor/fold change in buccal pEGFR.
Full Information
NCT ID
NCT00904345
First Posted
May 17, 2009
Last Updated
February 3, 2021
Sponsor
University of Michigan Rogel Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT00904345
Brief Title
Study of Radiation (RT) Concurrent With Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma (SCC)
Official Title
Phase II Study of RT Concurrent w/ Cetuximab in Patients w/ Locally Advanced Head & Neck SCC Who Do Not Qualify For Standard Chemotherapy Due To Age >70 Or Co-Morbidities
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
Stopped early for funding and efficacy reasons.
Study Start Date
April 2009 (undefined)
Primary Completion Date
December 2020 (Actual)
Study Completion Date
December 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a single-arm, phase II trial to characterize the clinical outcome of standard of care, cetuximab concurrent with radiation, in a special population (head and neck cancer patients who cannot tolerate concurrent chemoradiotherapy due to advanced age, poor performance status or concurrent illness), and to determine if biomarker response to a loading dose of cetuximab is predictive of that outcome.
Detailed Description
Primary Objective 1: Determine changes in tumor EGFR, pEGFR, downstream signaling and novel phosphoproteins following a loading dose of cetuximab in patients who are poor candidates for chemoradiation (age =70 years or with significant co-morbidities) and are therefore treated with cetuximab with radiation.
Primary Objective 2: Characterize clinical outcomes, including local recurrence, progression-free survival and overall survival in these patients, and correlate these clinical outcomes with the changes in tumor EGFR, pEGFR, downstream signaling, and novel phosphoproteins.
Primary Objective 3: Describe the toxicity, in particular mucositis/dysphagia, of this regimen.
Secondary Objective 1: Conduct normal mucosa EGFR assessment for comparison with tumor sample.
Secondary Objective 2: Correlate HPV presence and titer with p53 status and clinical outcome.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
SCC Head and Neck Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Intervention Description
Patients will receive a single dose of cetuximab 400 mg/m (Day 0). On day 7 (+/- 1 day), a repeat biopsy will be performed. Radiation concurrent with weekly cetuximab 250 mg/m.
Intervention Type
Radiation
Intervention Name(s)
50-60 Gy and 70 Gy
Intervention Description
Within approximately 4 days (after single dose of Cetuximab), definitive radiation will begin (70 Gy in 35 fractions to the gross tumor, 50-60 Gy to subclinical target volumes) concurrent with weekly cetuximab 250 mg/m.
Primary Outcome Measure Information:
Title
Mean Change in Tumor Epidermal Growth Factor Receptor (EGFR)
Description
The ratio (fold change) of tumor EGFR post-loading dose/pre-loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample.
Time Frame
At baseline (pre-loading dose) and day 7 post-loading dose
Title
Mean Change in Tumor Phosphorylated EGFR (pEGFR)
Description
The ratio (fold change) of tumor pEGFR post-loading dose/pre-loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample.
Time Frame
At baseline (pre-loading dose) and day 7 post-loading dose
Title
Progression Free Survival Rate
Description
Percentage of participants who survived without recurrent disease, from the time of enrollment to 1 and 2 years.
Time Frame
At 1 and 2 years
Title
Overall Survival Rate
Description
Percentage of participants alive at 1 and 2 years after enrollment.
Time Frame
At 1 and 2 Years
Title
Number of Participants With Treatment Related Toxicities
Description
Toxicities are measured by number of participants who experience one or more types or indicator of toxicity, shown as all grades and grades 3-4. As each participant could have multiple toxicities, the total number of incidents outnumbers the number of participants. Toxicities are graded according to the CTCAE v4.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Change in Tumor EGFR Level Relative to EGFR in Normal Mucosa
Description
Normal mucosa EGFR was assessed for comparison with EGFR in tumor sample. The fold change in tumor EGFR level at post-loading dose/pre-loading dose of cetuximab, relative to fold change in normal mucosa EGFR level post-loading dose/pre-loading dose of cetuximab was summarized across all participants who had an evaluable tumor sample and normal mucosa sample. The value reported is the ratio of fold change in tumor/fold change in buccal EGFR.
Time Frame
At baseline (pre-loading dose) and day 7 post-loading dose
Title
Change in Tumor pEGFR Level Relative to pEGFR in Normal Mucosa
Description
Normal mucosa pEGFR was assessed for comparison with pEGFR in tumor sample. The fold change in tumor pEGFR level post-loading dose/pre loading dose of cetuximab, relative to fold change in normal mucosa pEGFR level post-loading dose/pre-loading dose of cetuximab was summarized across all participants who had an evaluable tumor sample and normal mucosa sample. The value reported is the ratio of fold change in tumor/fold change in buccal pEGFR.
Time Frame
At baseline (pre-loading dose) and day 7 post-loading dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have pathologically-confirmed, previously untreated, clinically accessible (without general anesthesia) locally advanced squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or nonresectable head and neck squamous cell carcinomas of the skin.
Patients will be limited to:
≥ 70 years of age, OR
with co-morbidities that preclude treatment with standard platinum-based chemotherapy, as determined by the treating physician, OR
KPS ≤ 80, OR
Creatinine clearance < 30 cc/min
Laboratory criteria:
WBC > 3500/ul
Granulocyte > 1500/ul
Platelet count > 100,000/ul
Total Bilirubin < 1.5 X ULN
AST and ALT < 2.5 X ULN
Patients must give documented informed consent to participate in this study.
Exclusion Criteria:
Prior head and neck malignancy, or history of other prior non-head and neck malignancy within the past 3 years (excluding skin cancer and early stage treated prostate cancer).
Prior head and neck radiation or chemotherapy.
Documented evidence of distant metastases.
Patients with nasopharyngeal carcinoma.
Any medical or psychiatric illness, which, in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment.
Patients with psychiatric/social situations that would limit compliance with study requirements are not eligible.
Patients with prior anti-epidermal growth-factor receptor antibody therapy (antibody or small molecule).
Patients residing in prison.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shruti Jolly, MD
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of Michigan Veterans Administration Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Radiation (RT) Concurrent With Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma (SCC)
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