Brief Summary
This phase III trial compares cetuxumab to chemotherapy, carboplatin and paclitaxel, with intensity modulated radiation therapy for the treatment of patients with head and neck cancer who are unable to receive cisplatin. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of cancer cells. This may help keep cancer cells from growing. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Intensity modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. It is not yet know if cetxiumab or chemotherapy, with intensity modulated radiation therapy works best for the treatment of patients with head and neck cancer who are unable to receive cisplatin.
Brief Title
Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Head and Neck Cancer Who Cannot Receive Cisplatin
Detailed Description
PRIMARY OBJECTIVE:
I. To determine whether radiation therapy (RT) and concurrent carboplatin and paclitaxel (RT + carboplatin and paclitaxel \[CP\]) improves progression-free survival (PFS) compared to RT with concurrent cetuximab (RT + cetuximab \[Cetux\]) in patients with locoregionally advanced head and neck cancer (HNC) who have a contraindication to cisplatin.
SECONDARY OBJECTIVES:
I. To compare overall survival (OS) between RT+CP versus (vs.) RT + Cetux. II. To compare PFS and OS by study arm within p16-negative and p16-positive subgroups.
III. To compare safety and toxicity of RT+CP vs. RT + Cetux. IV. To compare patterns of failure (locoregional and distant) and competing causes of death of RT+CP vs. RT + Cetux.
V. To compare changes in diet, eating, and speech behaviors between RT+CP vs. RT + Cetux.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients undergo intensity modulated radiation therapy (IMRT) 5 days per week for 35 treatments. Starting within 7 days prior to radiation, patients receive a loading dose of cetuximab intravenously (IV) and then concurrently with radiation on day 1 of each cycle. Cycles repeat every 7 days for 7 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, positron emission tomography (PET) scan on study and blood sample collection throughout the study. Patients may undergo PET scan or magnetic resonance imaging (MRI) during screening.
ARM 2: Patients undergo IMRT 5 days per week for 35 treatments. Starting on day 1 of radiation, patients receive concurrent carboplatin IV and paclitaxel on day 1 of each cycle. Cycles repeat every 7 days for 7 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, PET scan on study and blood sample collection throughout the study. Patients may undergo PET scan or MRI during screening.
After completion of study treatment, patients are followed up at 30 days and then 4, 6, 12, 18, 24, 30 and 36 months then annually thereafter.
I. To determine whether radiation therapy (RT) and concurrent carboplatin and paclitaxel (RT + carboplatin and paclitaxel \[CP\]) improves progression-free survival (PFS) compared to RT with concurrent cetuximab (RT + cetuximab \[Cetux\]) in patients with locoregionally advanced head and neck cancer (HNC) who have a contraindication to cisplatin.
SECONDARY OBJECTIVES:
I. To compare overall survival (OS) between RT+CP versus (vs.) RT + Cetux. II. To compare PFS and OS by study arm within p16-negative and p16-positive subgroups.
III. To compare safety and toxicity of RT+CP vs. RT + Cetux. IV. To compare patterns of failure (locoregional and distant) and competing causes of death of RT+CP vs. RT + Cetux.
V. To compare changes in diet, eating, and speech behaviors between RT+CP vs. RT + Cetux.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients undergo intensity modulated radiation therapy (IMRT) 5 days per week for 35 treatments. Starting within 7 days prior to radiation, patients receive a loading dose of cetuximab intravenously (IV) and then concurrently with radiation on day 1 of each cycle. Cycles repeat every 7 days for 7 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, positron emission tomography (PET) scan on study and blood sample collection throughout the study. Patients may undergo PET scan or magnetic resonance imaging (MRI) during screening.
ARM 2: Patients undergo IMRT 5 days per week for 35 treatments. Starting on day 1 of radiation, patients receive concurrent carboplatin IV and paclitaxel on day 1 of each cycle. Cycles repeat every 7 days for 7 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, PET scan on study and blood sample collection throughout the study. Patients may undergo PET scan or MRI during screening.
After completion of study treatment, patients are followed up at 30 days and then 4, 6, 12, 18, 24, 30 and 36 months then annually thereafter.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
CLINICAL STAGE I HPV-MEDIATED (P16-POSITIVE) OROPHARYNGEAL CARCINOMA AJCC V8
CLINICAL STAGE II HPV-MEDIATED (P16-POSITIVE) OROPHARYNGEAL CARCINOMA AJCC V8
CLINICAL STAGE III HPV-MEDIATED (P16-POSITIVE) OROPHARYNGEAL CARCINOMA AJCC V8
HEAD AND NECK SQUAMOUS CELL CARCINOMA
STAGE III HYPOPHARYNGEAL CARCINOMA AJCC V8
STAGE III LARYNGEAL CANCER AJCC V8
STAGE III LIP AND ORAL CAVITY CANCER AJCC V8
STAGE III OROPHARYNGEAL (P16-NEGATIVE) CARCINOMA AJCC V8
STAGE IVA HYPOPHARYNGEAL CARCINOMA AJCC V8
STAGE IVA LARYNGEAL CANCER AJCC V8
STAGE IVA LIP AND ORAL CAVITY CANCER AJCC V8
STAGE IVA OROPHARYNGEAL (P16-NEGATIVE) CARCINOMA AJCC V8
STAGE IVB HYPOPHARYNGEAL CARCINOMA AJCC V8
STAGE IVB LARYNGEAL CANCER AJCC V8
STAGE IVB LIP AND ORAL CAVITY CANCER AJCC V8
STAGE IVB OROPHARYNGEAL (P16-NEGATIVE) CARCINOMA AJCC V8
Eligibility Criteria
Inclusion Criteria:
* Patients must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, or oral cavity
* Local evaluation of p16 status is required for all oropharynx patients prior to registration
* Local evaluation of p16 status is recommended for non-oropharynx patients prior to registration
* Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) defined as:
* Non-oropharynx and p16-negative oropharynx cancer: American Joint Commission on Cancer (AJCC) 8th edition stage III-IVB
* Laryngeal, Hypopharyngeal, Oral Cavity, and p16-Negative Oropharyngeal Primaries:
* AJCC 8th Edition TNM: T3-4b N0 M0 AJCC 8th Edition Stage: III-IVB
* AJCC 8th Edition TNM: T1-4b N1-3 M0 AJCC 8th Edition Stage: III-IVB
* p16-positive oropharynx cancer: AJCC 8th edition stage III and selected stage I-II based on smoking status in pack-years
* Eligible p16-Positive Oropharyngeal Primaries
* AJCC 8th Edition TNM: T1-2 N1 M0 AJCC 8th Edition Stage: I Pack-Years: \> 10
* AJCC 8th Edition TNM: T1-2 N2 M0 AJCC 8th Edition Stage: II Pack-Years: any
* AJCC 8th Edition TNM: T3 N0-1 M0 AJCC 8th Edition Stage: II Pack-Years: \> 10
* AJCC 8th Edition TNM: T3 N2 M0 AJCC 8th Edition Stage: II Pack-Years: any
* AJCC 8th Edition TNM: T1-3 N3 M0 AJCC 8th Edition Stage: III Pack-Years: any
* AJCC 8th Edition TNM: T4 N0-3 M0 AJCC 8th Edition Stage: III Pack-Years: any
* Note: Number of pack-years = \[Frequency of smoking (number of cigarettes per day) × duration of cigarette smoking (years)\] / 20
* Note: Cigar and pipe tobacco consumption is not included in calculating the lifetime pack-years. Marijuana consumption is likewise not considered in this calculation. There is also no clear scientific evidence regarding the role of chewing tobacco-containing products in oropharyngeal cancer, although this is possibly more concerning given the proximity of the oral cavity and oropharynx. In any case, investigators should not count use of non-cigarette tobacco products in the pack-years calculation
* The following are required prior to registration:
* Imaging of the head and neck with a neck CT or MRI (with contrast, unless contraindicated) or PET/CT which includes diagnostic-quality CT of the neck (with contrast, unless contraindicated)
* Chest imaging: Chest CT (with contrast, unless contraindicated) or PET/CT
* Age ≥ 18
* Complete the online tool at www.nrgoncology.org prior to registration and record the (modified) Charleston Comorbidity Index (CCI), Head and Neck Cancer Intergroup (HNCIG) omega, and G-8 scores on the registration form in Oncology Patient Enrollment Network (OPEN)
* Patients must have a contraindication to cisplatin as defined in the following bullet points:
* Absolute or relative contraindication to cisplatin, defined as ONE OR MORE of the following prior to registration:
* Creatinine clearance (CrCl) \< 60 mL/min by the Cockroft-Gault formula
* Pre-existing peripheral (sensory or motor) neuropathy grade ≥ 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0)
* History of hearing loss, defined as either:
* Existing need of a hearing aid OR
* ≥ 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated OR
* age ≥ 70 with Head and Neck Cancer Intergroup (HNCIG) omega score \< 0.80 prior to registration OR
* Age \< 70 with ALL of the following conditions prior to registration (see Appendix II for calculation instructions):
* HNCIG omega score \< 0.80
* (Modified) Charlson Comorbidity Index (CCI) ≥ 1
* G-8 score ≤ 14
* Not pregnant and not nursing
* Participants must be able to safely receive the radiation and drug regimens per current Food and Drug Administration (FDA)-approved package insert(s), treating investigator's discretion, and institutional guidelines
* No prior systemic therapy for the study cancer; note that prior systemic therapy for a different cancer is allowable
* No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* No prior surgery for the study cancer
* Patients must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, or oral cavity
* Local evaluation of p16 status is required for all oropharynx patients prior to registration
* Local evaluation of p16 status is recommended for non-oropharynx patients prior to registration
* Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) defined as:
* Non-oropharynx and p16-negative oropharynx cancer: American Joint Commission on Cancer (AJCC) 8th edition stage III-IVB
* Laryngeal, Hypopharyngeal, Oral Cavity, and p16-Negative Oropharyngeal Primaries:
* AJCC 8th Edition TNM: T3-4b N0 M0 AJCC 8th Edition Stage: III-IVB
* AJCC 8th Edition TNM: T1-4b N1-3 M0 AJCC 8th Edition Stage: III-IVB
* p16-positive oropharynx cancer: AJCC 8th edition stage III and selected stage I-II based on smoking status in pack-years
* Eligible p16-Positive Oropharyngeal Primaries
* AJCC 8th Edition TNM: T1-2 N1 M0 AJCC 8th Edition Stage: I Pack-Years: \> 10
* AJCC 8th Edition TNM: T1-2 N2 M0 AJCC 8th Edition Stage: II Pack-Years: any
* AJCC 8th Edition TNM: T3 N0-1 M0 AJCC 8th Edition Stage: II Pack-Years: \> 10
* AJCC 8th Edition TNM: T3 N2 M0 AJCC 8th Edition Stage: II Pack-Years: any
* AJCC 8th Edition TNM: T1-3 N3 M0 AJCC 8th Edition Stage: III Pack-Years: any
* AJCC 8th Edition TNM: T4 N0-3 M0 AJCC 8th Edition Stage: III Pack-Years: any
* Note: Number of pack-years = \[Frequency of smoking (number of cigarettes per day) × duration of cigarette smoking (years)\] / 20
* Note: Cigar and pipe tobacco consumption is not included in calculating the lifetime pack-years. Marijuana consumption is likewise not considered in this calculation. There is also no clear scientific evidence regarding the role of chewing tobacco-containing products in oropharyngeal cancer, although this is possibly more concerning given the proximity of the oral cavity and oropharynx. In any case, investigators should not count use of non-cigarette tobacco products in the pack-years calculation
* The following are required prior to registration:
* Imaging of the head and neck with a neck CT or MRI (with contrast, unless contraindicated) or PET/CT which includes diagnostic-quality CT of the neck (with contrast, unless contraindicated)
* Chest imaging: Chest CT (with contrast, unless contraindicated) or PET/CT
* Age ≥ 18
* Complete the online tool at www.nrgoncology.org prior to registration and record the (modified) Charleston Comorbidity Index (CCI), Head and Neck Cancer Intergroup (HNCIG) omega, and G-8 scores on the registration form in Oncology Patient Enrollment Network (OPEN)
* Patients must have a contraindication to cisplatin as defined in the following bullet points:
* Absolute or relative contraindication to cisplatin, defined as ONE OR MORE of the following prior to registration:
* Creatinine clearance (CrCl) \< 60 mL/min by the Cockroft-Gault formula
* Pre-existing peripheral (sensory or motor) neuropathy grade ≥ 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0)
* History of hearing loss, defined as either:
* Existing need of a hearing aid OR
* ≥ 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated OR
* age ≥ 70 with Head and Neck Cancer Intergroup (HNCIG) omega score \< 0.80 prior to registration OR
* Age \< 70 with ALL of the following conditions prior to registration (see Appendix II for calculation instructions):
* HNCIG omega score \< 0.80
* (Modified) Charlson Comorbidity Index (CCI) ≥ 1
* G-8 score ≤ 14
* Not pregnant and not nursing
* Participants must be able to safely receive the radiation and drug regimens per current Food and Drug Administration (FDA)-approved package insert(s), treating investigator's discretion, and institutional guidelines
* No prior systemic therapy for the study cancer; note that prior systemic therapy for a different cancer is allowable
* No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* No prior surgery for the study cancer
Inclusion Criteria
Inclusion Criteria:
* Patients must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, or oral cavity
* Local evaluation of p16 status is required for all oropharynx patients prior to registration
* Local evaluation of p16 status is recommended for non-oropharynx patients prior to registration
* Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) defined as:
* Non-oropharynx and p16-negative oropharynx cancer: American Joint Commission on Cancer (AJCC) 8th edition stage III-IVB
* Laryngeal, Hypopharyngeal, Oral Cavity, and p16-Negative Oropharyngeal Primaries:
* AJCC 8th Edition TNM: T3-4b N0 M0 AJCC 8th Edition Stage: III-IVB
* AJCC 8th Edition TNM: T1-4b N1-3 M0 AJCC 8th Edition Stage: III-IVB
* p16-positive oropharynx cancer: AJCC 8th edition stage III and selected stage I-II based on smoking status in pack-years
* Eligible p16-Positive Oropharyngeal Primaries
* AJCC 8th Edition TNM: T1-2 N1 M0 AJCC 8th Edition Stage: I Pack-Years: \> 10
* AJCC 8th Edition TNM: T1-2 N2 M0 AJCC 8th Edition Stage: II Pack-Years: any
* AJCC 8th Edition TNM: T3 N0-1 M0 AJCC 8th Edition Stage: II Pack-Years: \> 10
* AJCC 8th Edition TNM: T3 N2 M0 AJCC 8th Edition Stage: II Pack-Years: any
* AJCC 8th Edition TNM: T1-3 N3 M0 AJCC 8th Edition Stage: III Pack-Years: any
* AJCC 8th Edition TNM: T4 N0-3 M0 AJCC 8th Edition Stage: III Pack-Years: any
* Note: Number of pack-years = \[Frequency of smoking (number of cigarettes per day) × duration of cigarette smoking (years)\] / 20
* Note: Cigar and pipe tobacco consumption is not included in calculating the lifetime pack-years. Marijuana consumption is likewise not considered in this calculation. There is also no clear scientific evidence regarding the role of chewing tobacco-containing products in oropharyngeal cancer, although this is possibly more concerning given the proximity of the oral cavity and oropharynx. In any case, investigators should not count use of non-cigarette tobacco products in the pack-years calculation
* The following are required prior to registration:
* Imaging of the head and neck with a neck CT or MRI (with contrast, unless contraindicated) or PET/CT which includes diagnostic-quality CT of the neck (with contrast, unless contraindicated)
* Chest imaging: Chest CT (with contrast, unless contraindicated) or PET/CT
* Age ≥ 18
* Complete the online tool at www.nrgoncology.org prior to registration and record the (modified) Charleston Comorbidity Index (CCI), Head and Neck Cancer Intergroup (HNCIG) omega, and G-8 scores on the registration form in Oncology Patient Enrollment Network (OPEN)
* Patients must have a contraindication to cisplatin as defined in the following bullet points:
* Absolute or relative contraindication to cisplatin, defined as ONE OR MORE of the following prior to registration:
* Creatinine clearance (CrCl) \< 60 mL/min by the Cockroft-Gault formula
* Pre-existing peripheral (sensory or motor) neuropathy grade ≥ 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0)
* History of hearing loss, defined as either:
* Existing need of a hearing aid OR
* ≥ 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated OR
* age ≥ 70 with Head and Neck Cancer Intergroup (HNCIG) omega score \< 0.80 prior to registration OR
* Age \< 70 with ALL of the following conditions prior to registration (see Appendix II for calculation instructions):
* HNCIG omega score \< 0.80
* (Modified) Charlson Comorbidity Index (CCI) ≥ 1
* G-8 score ≤ 14
* Not pregnant and not nursing
* Participants must be able to safely receive the radiation and drug regimens per current Food and Drug Administration (FDA)-approved package insert(s), treating investigator's discretion, and institutional guidelines
* No prior systemic therapy for the study cancer; note that prior systemic therapy for a different cancer is allowable
* No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* No prior surgery for the study cancer
* Patients must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, or oral cavity
* Local evaluation of p16 status is required for all oropharynx patients prior to registration
* Local evaluation of p16 status is recommended for non-oropharynx patients prior to registration
* Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) defined as:
* Non-oropharynx and p16-negative oropharynx cancer: American Joint Commission on Cancer (AJCC) 8th edition stage III-IVB
* Laryngeal, Hypopharyngeal, Oral Cavity, and p16-Negative Oropharyngeal Primaries:
* AJCC 8th Edition TNM: T3-4b N0 M0 AJCC 8th Edition Stage: III-IVB
* AJCC 8th Edition TNM: T1-4b N1-3 M0 AJCC 8th Edition Stage: III-IVB
* p16-positive oropharynx cancer: AJCC 8th edition stage III and selected stage I-II based on smoking status in pack-years
* Eligible p16-Positive Oropharyngeal Primaries
* AJCC 8th Edition TNM: T1-2 N1 M0 AJCC 8th Edition Stage: I Pack-Years: \> 10
* AJCC 8th Edition TNM: T1-2 N2 M0 AJCC 8th Edition Stage: II Pack-Years: any
* AJCC 8th Edition TNM: T3 N0-1 M0 AJCC 8th Edition Stage: II Pack-Years: \> 10
* AJCC 8th Edition TNM: T3 N2 M0 AJCC 8th Edition Stage: II Pack-Years: any
* AJCC 8th Edition TNM: T1-3 N3 M0 AJCC 8th Edition Stage: III Pack-Years: any
* AJCC 8th Edition TNM: T4 N0-3 M0 AJCC 8th Edition Stage: III Pack-Years: any
* Note: Number of pack-years = \[Frequency of smoking (number of cigarettes per day) × duration of cigarette smoking (years)\] / 20
* Note: Cigar and pipe tobacco consumption is not included in calculating the lifetime pack-years. Marijuana consumption is likewise not considered in this calculation. There is also no clear scientific evidence regarding the role of chewing tobacco-containing products in oropharyngeal cancer, although this is possibly more concerning given the proximity of the oral cavity and oropharynx. In any case, investigators should not count use of non-cigarette tobacco products in the pack-years calculation
* The following are required prior to registration:
* Imaging of the head and neck with a neck CT or MRI (with contrast, unless contraindicated) or PET/CT which includes diagnostic-quality CT of the neck (with contrast, unless contraindicated)
* Chest imaging: Chest CT (with contrast, unless contraindicated) or PET/CT
* Age ≥ 18
* Complete the online tool at www.nrgoncology.org prior to registration and record the (modified) Charleston Comorbidity Index (CCI), Head and Neck Cancer Intergroup (HNCIG) omega, and G-8 scores on the registration form in Oncology Patient Enrollment Network (OPEN)
* Patients must have a contraindication to cisplatin as defined in the following bullet points:
* Absolute or relative contraindication to cisplatin, defined as ONE OR MORE of the following prior to registration:
* Creatinine clearance (CrCl) \< 60 mL/min by the Cockroft-Gault formula
* Pre-existing peripheral (sensory or motor) neuropathy grade ≥ 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0)
* History of hearing loss, defined as either:
* Existing need of a hearing aid OR
* ≥ 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated OR
* age ≥ 70 with Head and Neck Cancer Intergroup (HNCIG) omega score \< 0.80 prior to registration OR
* Age \< 70 with ALL of the following conditions prior to registration (see Appendix II for calculation instructions):
* HNCIG omega score \< 0.80
* (Modified) Charlson Comorbidity Index (CCI) ≥ 1
* G-8 score ≤ 14
* Not pregnant and not nursing
* Participants must be able to safely receive the radiation and drug regimens per current Food and Drug Administration (FDA)-approved package insert(s), treating investigator's discretion, and institutional guidelines
* No prior systemic therapy for the study cancer; note that prior systemic therapy for a different cancer is allowable
* No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* No prior surgery for the study cancer
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07441681
Org Class
Other
Org Full Name
NRG Oncology
Org Study Id
NRG-HN016
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Radiotherapy With Concurrent Cetuximab vs. Carboplatin and Paclitaxel in Patients With Stage III-IVB Head and Neck Cancer With a Contraindication to Cisplatin: A Pragmatic Phase III Randomized Trial
Primary Outcomes
Outcome Description
The PFS rates for each treatment arm will be estimated in the overall sample and within each p16 subgroup using the Kaplan-Meier method. Estimates of the median PFS and 2-year PFS rates will be obtained with 90% confidence intervals. The comparison of PFS distributions between each treatment arm will be performed using a one-sided stratified log-rank test (stratified by the randomization stratification factors). As additional analysis of treatment effect, multivariable analysis will be performed using a Cox proportional hazards model, where the stratification factors, and relevant patient and tumor characteristics are included (as measured by the model's Bayesian Information Criterion \[BIC\]). Hazard ratios and their respective 90% confidence intervals will be provided.
Outcome Measure
Progression free survival (PFS)
Outcome Time Frame
From randomization until locoregional failure, distant failure, or death due to any cause, up to 8 years
Secondary Ids
Secondary Id
NCI-2026-00811
Secondary Id
NRG-HN016
Secondary Id
NRG-HN016
Secondary Id
U10CA180868
Secondary Outcomes
Outcome Description
Will be summarized by treatment arm using standard Kaplan-Meier methods, where estimates of the median and 2-year OS will be obtained with 90% confidence intervals. The OS will be compared using a one-sided stratified log-rank test, stratified by the randomization strata.
Outcome Time Frame
From randomization until death due to any cause, up to 8 years
Outcome Measure
Overall survival (OS)
Outcome Description
Assessments within p16 subgroups is to compare treatment arms within potentially clinically relevant subgroups. Within p16-negative and p16-positive subgroups, the OS will be summarized by study arm using standard Kaplan-Meier methods. The median OS and 2-year OS rates will be reported with 90% confidence intervals. Comparisons will be made using one-sided stratified log-rank tests. Multivariate Cox regression models will also be considered, where relevant covariates are selected based on the model's BIC.
Outcome Time Frame
From randomization until death due to any cause, up to 8 years
Outcome Measure
OS by p16 status
Outcome Description
PFS assessments within p16 subgroups is to compare treatment arms within potentially clinically relevant subgroups. Within p16-negative and p16-positive subgroups, the PFS will be summarized by study arm using standard Kaplan-Meier methods. The median PFS and 2-year PFS rates will be reported with 90% confidence intervals. Comparisons will be made using one-sided stratified log-rank tests. Multivariate Cox regression models will also be considered, where relevant covariates are selected based on the model's BIC. No adjustments will be made for multiplicity.
Outcome Time Frame
From randomization until locoregional failure, distant failure, or death due to any cause, up to 8 years
Outcome Measure
PFS by p16 status
Outcome Description
Adverse event grades will be assessed by Common Terminology Criteria for Adverse Events version 5.0. The overall (highest grade) adverse events will be summarized by treatment arm using frequencies and relative frequencies.
Outcome Time Frame
Up to 24 months from end of radiation therapy (RT)
Outcome Measure
Incidence of adverse events
Outcome Description
Patient responses will be summarized by treatment arm and time point using frequencies and relative frequencies.
Outcome Time Frame
Up to 12 months from end of RT
Outcome Measure
Incidence of patient reported incidence of adverse events
Outcome Description
Will compare patterns of failure and competing causes of death between treatment arms. The number and type of failures will be summarized by treatment arm using frequencies and relative frequencies. The time to failure will be summarized by treatment arm using the cumulative incidence method, where estimates of the 2-year failure rates will be obtained with 90% confidence intervals. Comparisons between treatment arms will be made using the stratified Gray's test.
Outcome Time Frame
From randomization until first evidence of local, regional disease progression or recurrence, or death from study cancer, up to 8 years
Outcome Measure
Time to locoregional failure
Outcome Description
Will compare patterns of failure and competing causes of death between treatment arms. The number and type of failures will be summarized by treatment arm using frequencies and relative frequencies. The time to failure will be summarized by treatment arm using the cumulative incidence method, where estimates of the 2-year failure rates will be obtained with 90% confidence intervals. Comparisons between treatment arms will be made using the stratified Gray's test.
Outcome Time Frame
From randomization until first evidence of distant metastasis, up to 8 years
Outcome Measure
Time to distant failure
Outcome Description
Will compare patterns of failure and competing causes of death between treatment arms. The number and type of failures will be summarized by treatment arm using frequencies and relative frequencies. The time to failure will be summarized by treatment arm using the cumulative incidence method, where estimates of the 2-year failure rates will be obtained with 90% confidence intervals. Comparisons between treatment arms will be made using the stratified Gray's test.
Outcome Time Frame
From randomization until death due to other or unknown causes, up to 8 years
Outcome Measure
Time to competing mortality
Outcome Description
Assessed via the Performance Status Scale for Head and Neck Cancer. The mean score change (relative to end of radiation treatment) for each of these subscales between arms will be compared at 12 months post-RT using a two-sample independent t-test with a two-sided significance level of 0.05. A Wilcoxon test will be used if normality assumption does not hold. Temporal trends and differences between arms at other time points will be assessed using mixed models with the following covariates: time, treatment arm and its interaction.
Outcome Time Frame
At baseline, end of treatment, 4, 6 and 12 months from end of RT
Outcome Measure
Longitudinal eating/speech profiles
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Rafi Kabarriti
Investigator Email
RKABARRI@MONTEFIORE.ORG
Investigator Sponsor Organization
External
Study Department
Radiation Oncology
Study Division
Radiation Oncology
Categories Mesh Debug
Cancer --- CARCINOMA
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Digestive System --- STOMATOGNATHIC DISEASES
Head & Neck --- OTORHINOLARYNGOLOGIC DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Digestive System --- MOUTH DISEASES
MeSH Terms
OROPHARYNGEAL NEOPLASMS
SQUAMOUS CELL CARCINOMA OF HEAD AND NECK
HYPOPHARYNGEAL NEOPLASMS
LARYNGEAL NEOPLASMS
MOUTH NEOPLASMS
CARCINOMA
PHARYNGEAL NEOPLASMS
OTORHINOLARYNGOLOGIC NEOPLASMS
HEAD AND NECK NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
PHARYNGEAL DISEASES
STOMATOGNATHIC DISEASES
OTORHINOLARYNGOLOGIC DISEASES
CARCINOMA, SQUAMOUS CELL
NEOPLASMS, GLANDULAR AND EPITHELIAL
NEOPLASMS BY HISTOLOGIC TYPE
LARYNGEAL DISEASES
RESPIRATORY TRACT DISEASES
RESPIRATORY TRACT NEOPLASMS
MOUTH DISEASES
SPECIMEN HANDLING
CARBOPLATIN
CETUXIMAB
(225)AC-DOTA-C(RGDYK)
RADIOTHERAPY, INTENSITY-MODULATED
MAGNETIC RESONANCE SPECTROSCOPY
PACLITAXEL
TAXES
CLINICAL LABORATORY TECHNIQUES
DIAGNOSTIC TECHNIQUES AND PROCEDURES
DIAGNOSIS
INVESTIGATIVE TECHNIQUES
COORDINATION COMPLEXES
ORGANIC CHEMICALS
ANTIBODIES, MONOCLONAL, HUMANIZED
ANTIBODIES, MONOCLONAL
ANTIBODIES
IMMUNOGLOBULINS
IMMUNOPROTEINS
BLOOD PROTEINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS
SERUM GLOBULINS
GLOBULINS
RADIOTHERAPY, CONFORMAL
RADIOTHERAPY, COMPUTER-ASSISTED
RADIOTHERAPY
THERAPEUTICS
SPECTRUM ANALYSIS
CHEMISTRY TECHNIQUES, ANALYTICAL
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
DITERPENES
TERPENES
ECONOMICS
HEALTH CARE ECONOMICS AND ORGANIZATIONS