Cetuximab and Radiation Therapy in Treating Patients With Stage III-IV Head and Neck Cancer
Primary Purpose
Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Oropharynx
Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
cetuximab
cisplatin
external beam radiation therapy
laboratory biomarker analysis
Sponsored by
About this trial
This is an interventional treatment trial for Stage III Squamous Cell Carcinoma of the Hypopharynx
Eligibility Criteria
Inclusion Criteria:
- Histologically proven squamous cell carcinoma of the oropharynx, hypopharynx or larynx
- Stage III/IVa/b squamous cell carcinoma (SCC) by American Joint Committee on Cancer (AJCC) 7 criteria (advanced, but not metastatic)
- Patients must give informed consent
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Platelets >= 100,000/uL
- Absolute neutrophil count (ANC) >= 1,500/uL
- Hemoglobin > 8 g/dl (use of transfusion to achieve this is acceptable)
- Total bilirubin < 2 X institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional ULN
- Serum creatinine < 2 x institutional ULN or creatinine clearance > 50 ml/min as determined by 24 hour collection or estimated by Cockcroft-Gault formula
- Estimated life expectancy of at least 12 weeks
- Negative pregnancy test
Exclusion Criteria:
- Patients may not have received previous therapy for their head and neck SCC, including chemotherapy, radiation therapy, or surgery beyond biopsy
- Second primary malignancy; exceptions are 1) patient had a second primary malignancy but has been treated and disease free for at least 3 years, 2) in situ carcinoma (e.g. in situ carcinoma of the cervix), 3) non-melanomatous carcinoma of the skin
- Patients with metastatic disease beyond the neck and supraclavicular region will be excluded
- Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator; this includes scleroderma
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab or cisplatinum or other agents used in the study
- Women who are pregnant; women of childbearing age must agree to undergo a pregnancy test prior to therapy and to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 6 months after; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Patients with human immunodeficiency virus (HIV) infection are not automatically excluded, but must meet the following criteria: cluster of differentiation (CD)4 count is > 499/cu mm and their viral load is < 50 copies/ml; use of highly active anti-retroviral therapy (HAART) is allowed
- Patients who have had either myocardial infarction, coronary artery bypass graft, coronary artery stenting, hospital admission for heart related issues such as congestive heart failure or arrhythmia within the last 3 months, will not be allowed on protocol
Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events [CTCAE], version [v]. 4):
- Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels
- Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels
- Potassium < 3.5 mmol/L or > 6 mmol/L despite intervention to normalize levels
- Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels
Sites / Locations
- New Jersey Medical School
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (cetuximab, cisplatin, EBRT)
Arm Description
Patients receive cetuximab IV over 60-120 minutes for 3 weeks. Patients then undergo EBRT over 6-7 weeks. Patients achieving response continue weekly doses of cetuximab until radiation therapy is completed. Patients unable to achieve response or progression receive cisplatin IV over 1-2 hours on days 1, 22, and 43 of radiation therapy.
Outcomes
Primary Outcome Measures
Locoregional Control in Cetuximab Responders
Target number of patients for the study was 27. At the termination of the study, 8 patients were accrued and finished treatment but 1 patient dropped out before follow up, leaving an evaluable number of 7. As the enrollment in the study did not reach the target number of patients, we were not able to produce statistically reliable results to detect the expected difference. Therefore, we have decided to provide summary statistics of primary and secondary outcomes.
Among 3 cetuximab responders, two did not have progression within 2 year follow-up time and one had a locoregional recurrence and expired.
Secondary Outcome Measures
Percent of Patients Who Progress During Neoadjuvant Cetuximab by CT RECIST 1.1 Criteria
Among 7 patients, no one progressed during neoadjuvant cetuximab per RECIST 1.1 CT criteria (0%).
Locoregional Control for Non-responders to Neoadjuvant Cetuximab
Among 4 cetuximab non-responders, none had locoregional failure at 2 years. Two patients had known HPV status; one patient was HPV+ and another patient HPV-. HPV status for the other two was unknown. HPV positive patient had no sign of progression within 2 years of follow-up. HPV negative patient had no sign of progression for 210 days until the last follow-up. One HPV unknown patient did not show progression within 2 years of follow-up, and the other HPV unknown patient had no progression for 115 days until the last follow-up.
Full Information
NCT ID
NCT02177838
First Posted
June 26, 2014
Last Updated
April 19, 2021
Sponsor
Rutgers, The State University of New Jersey
Collaborators
National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
1. Study Identification
Unique Protocol Identification Number
NCT02177838
Brief Title
Cetuximab and Radiation Therapy in Treating Patients With Stage III-IV Head and Neck Cancer
Official Title
Selecting for Cetuximab Responders in Advanced Head and Neck SCC
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual
Study Start Date
March 25, 2015 (Actual)
Primary Completion Date
August 22, 2019 (Actual)
Study Completion Date
August 22, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rutgers, The State University of New Jersey
Collaborators
National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This pilot clinical trial studies cetuximab and radiation therapy in treating patients with stage III-IV head and neck cancer. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways by targeting certain cells. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving cetuximab or cisplatin together with radiation therapy may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES:
I. 2 year (yr) locoregional control in cetuximab responders.
SECONDARY OBJECTIVES:
I. Assess secondary clinical endpoints such as the percent of patients receiving neoadjuvant cetuximab who progress by computed tomography (CT) Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria during the neoadjuvant cetuximab, the 2 yr locoregional control for non-responders to neoadjuvant cetuximab, and the complete response rate to positron emission tomography (PET)/computed tomography (CT) scan 3 months after the completion of radiation therapy for both responders and for non-responders to neoadjuvant cetuximab.
II. Analyze the relationship of known deoxyribonucleic acid (DNA) mutations in tumor per the FoundationOne genomic profile, and correlate to clinical endpoints such as locoregional control.
II. Analyze any changes in protein production at the tumor in response to 3 weeks of cetuximab.
III. Analyze any changes in protein production at the skin in response to 3 weeks of cetuximab.
IV. To investigate whether the tumor imaging characteristics including anatomical and molecular parameters evaluated by PET/CT, either alone or combined with other biomarkers can attribute to the better prediction for the clinical outcomes, as the response to neoadjuvant cetuximab; and the final clinical endpoint, the 2-year local regional controls.
OUTLINE:
Patients receive cetuximab intravenously (IV) over 60-120 minutes for 3 weeks. Patients then undergo external beam radiation therapy (EBRT) over 6-7 weeks. Patients achieving response continue weekly doses of cetuximab until radiation therapy is completed. Patients unable to achieve response or progression receive cisplatin IV over 1-2 hours on days 1, 22, and 43 of radiation therapy.
After completion of study treatment, patients are followed up every 3 months for 2 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage III Verrucous Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Verrucous Carcinoma of the Larynx, Tongue Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (cetuximab, cisplatin, EBRT)
Arm Type
Experimental
Arm Description
Patients receive cetuximab IV over 60-120 minutes for 3 weeks. Patients then undergo EBRT over 6-7 weeks. Patients achieving response continue weekly doses of cetuximab until radiation therapy is completed. Patients unable to achieve response or progression receive cisplatin IV over 1-2 hours on days 1, 22, and 43 of radiation therapy.
Intervention Type
Biological
Intervention Name(s)
cetuximab
Other Intervention Name(s)
C225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
CACP, CDDP, CPDD, DDP
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
external beam radiation therapy
Other Intervention Name(s)
EBRT
Intervention Description
Undergo EBRT
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Locoregional Control in Cetuximab Responders
Description
Target number of patients for the study was 27. At the termination of the study, 8 patients were accrued and finished treatment but 1 patient dropped out before follow up, leaving an evaluable number of 7. As the enrollment in the study did not reach the target number of patients, we were not able to produce statistically reliable results to detect the expected difference. Therefore, we have decided to provide summary statistics of primary and secondary outcomes.
Among 3 cetuximab responders, two did not have progression within 2 year follow-up time and one had a locoregional recurrence and expired.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Percent of Patients Who Progress During Neoadjuvant Cetuximab by CT RECIST 1.1 Criteria
Description
Among 7 patients, no one progressed during neoadjuvant cetuximab per RECIST 1.1 CT criteria (0%).
Time Frame
Day 14-21 after the first dose of cetuximab
Title
Locoregional Control for Non-responders to Neoadjuvant Cetuximab
Description
Among 4 cetuximab non-responders, none had locoregional failure at 2 years. Two patients had known HPV status; one patient was HPV+ and another patient HPV-. HPV status for the other two was unknown. HPV positive patient had no sign of progression within 2 years of follow-up. HPV negative patient had no sign of progression for 210 days until the last follow-up. One HPV unknown patient did not show progression within 2 years of follow-up, and the other HPV unknown patient had no progression for 115 days until the last follow-up.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically proven squamous cell carcinoma of the oropharynx, hypopharynx or larynx
Stage III/IVa/b squamous cell carcinoma (SCC) by American Joint Committee on Cancer (AJCC) 7 criteria (advanced, but not metastatic)
Patients must give informed consent
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Platelets >= 100,000/uL
Absolute neutrophil count (ANC) >= 1,500/uL
Hemoglobin > 8 g/dl (use of transfusion to achieve this is acceptable)
Total bilirubin < 2 X institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional ULN
Serum creatinine < 2 x institutional ULN or creatinine clearance > 50 ml/min as determined by 24 hour collection or estimated by Cockcroft-Gault formula
Estimated life expectancy of at least 12 weeks
Negative pregnancy test
Exclusion Criteria:
Patients may not have received previous therapy for their head and neck SCC, including chemotherapy, radiation therapy, or surgery beyond biopsy
Second primary malignancy; exceptions are 1) patient had a second primary malignancy but has been treated and disease free for at least 3 years, 2) in situ carcinoma (e.g. in situ carcinoma of the cervix), 3) non-melanomatous carcinoma of the skin
Patients with metastatic disease beyond the neck and supraclavicular region will be excluded
Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator; this includes scleroderma
History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab or cisplatinum or other agents used in the study
Women who are pregnant; women of childbearing age must agree to undergo a pregnancy test prior to therapy and to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 6 months after; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Patients with human immunodeficiency virus (HIV) infection are not automatically excluded, but must meet the following criteria: cluster of differentiation (CD)4 count is > 499/cu mm and their viral load is < 50 copies/ml; use of highly active anti-retroviral therapy (HAART) is allowed
Patients who have had either myocardial infarction, coronary artery bypass graft, coronary artery stenting, hospital admission for heart related issues such as congestive heart failure or arrhythmia within the last 3 months, will not be allowed on protocol
Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events [CTCAE], version [v]. 4):
Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels
Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels
Potassium < 3.5 mmol/L or > 6 mmol/L despite intervention to normalize levels
Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sung Kim
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
New Jersey Medical School
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Cetuximab and Radiation Therapy in Treating Patients With Stage III-IV Head and Neck Cancer
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