Head and Neck Cancer, Squamous Cell Carcinoma
Conditions
Keywords
Head and Neck Cancer, panitumumab
Brief summary
The addition of chemotherapy to radiotherapy (chemoradiation) has improved outcomes for patients with locally advanced squamous cell carcinoma of the head and neck but additional improvements to treatment regimens are needed. The study is investigating if the addition of a targeted therapy (panitumumab) can improve the efficacy of chemoradiation without adding unmanageable toxicity.
Interventions
DRUGCisplatin
Administered intravenously (IV; in a vein)
RADIATIONStandard Fractionation Radiotherapy
70 Gy administered in 2 Gy fractions daily for 5 days a week for 7 weeks (35 fractions)
DRUGPanitumumab
Administered intravenously
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of Stage III or IVa-b (M0) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (you must be well enough to receive chemoradiation therapy) * You must be at least 18 years of age * Your test results must show that your kidneys, liver and blood cells are working adequately and that, if you are female, you are not pregnant * You must have measurable disease
Exclusion criteria
* Cancer of the nasopharynx, sinus, salivary gland or skin * History of another cancer (other than head and neck) unless treated with curative intent and with no evidence of disease for more than 3 years, with the exception of non-melanoma skin cancer or in situ cervical cancer * Previous treatment with anti-endothelial growth factor receptor (EGFr) antibody therapy or EGFr inhibitors * Previous treatment for head and neck cancer, with chemotherapy, surgery (except nodal sampling or biopsy) or radiotherapy * Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) within one year before you join the study * Chronic obstructive pulmonary disease (pneumonia or respiratory decompensation) resulting in hospitalization within 6 months of study screening * History or evidence of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) * Major surgery within 28 days of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local Regional Control Rate at 2 Years | 2 years | In this study participants were considered to be in local regional control (LRC) if there was no evidence of active disease in the previously affected/irradiated head-and-neck area. LRC could be achieved at any time following completion of treatment unless disease progression in the local-regional area occurred or the participant received subsequent anti-tumor therapy. Local regional control rate is defined as the Kaplan-Meier (KM) estimate of the proportion of participants with local regional control. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Local-regional Control | From first dose up to 37 months | Duration of local regional control is calculated from the first day of any study treatment (radiotherapy, chemotherapy, or panitumumab) administration to the date of first local-regional failure or to death due to any cause (whichever occurs first). Local-regional failure includes persistent disease and local-regional recurrence of disease. Participants who did not meet the criteria for LRC recurrence after achieving a response by the analysis data cutoff date were censored at their last evaluable disease assessment date. Participants who never achieved LRC were considered to have a duration of 0. |
| Progression-Free Survival | From first dose date to 37 months | Progression-free survival time is defined as time from the first day of any study treatment to date of first progresive disease using a modified version of the World Health Organization (WHO) criteria or death. Progressive Disease is defined as at least a 25% increase in the size of index lesions or unequivocal progression of existing non-index lesions or the presence of one or more new lesions. Participants not meeting these criteria by the cutoff date were censored at their last evaluable disease assessment date. |
| Local Regional Control Rate at 6 Months and 12 Months | 6 months and 12 months | Participants were considered to be in local regional control (LRC) if there was no evidence of active disease in the previously affected/irradiated head-and-neck area. LRC could be achieved at any time following completion of treatment unless disease progression in the local-regional area occurred or the participant received subsequent anti-tumor therapy. Local regional control rate is defined as the Kaplan-Meier (KM) estimate of the proportion of participants with local regional control. |
| Percentage of Participants With an Objective Response at 6 Months | 6 months | Objective response by 6 months is defined as a complete response or partial response based on central review of scans using a a modification of the WHO criteria during the first 6 months. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the size of index lesions with no progression in non-index lesions, or the disappearance of all index lesions and persistence of 1 or more non-index lesions not qualifying for either CR or progressive disease and no new lesions. |
| Percentage of Participants With a Complete Response at 6 Months | 6 months | Response assessment based on central review of scans using a a modification of the WHO criteria, during the first 6 months. Complete Response is defined as the disappearance of all index and non-index lesions and no new lesions. |
| Overall Survival | From first dose date up to 37 months | Survival time is defined as time from the first day of any study treatment to date of death. Participants who had not died by the cutoff date were censored at their last contact date. |
Participant flow
Recruitment details
153 patients were enrolled with 89 patients on panitumumab plus chemoradiation arm, and 64 patients on chemoradiotherapy alone arm.
Participants by arm
| Arm | Count |
|---|---|
| Panitumumab Plus Chemoradiation Participants received standard radiation therapy for 7 weeks, cisplatin 75 mg/m\^2 and panitumumab 9 mg/kg intravenously on Days 1, 22 and 43. | 89 |
| Chemoradiotherapy Alone Participants received standard radiation therapy for 7 weeks and cisplatin 100 mg/m\^2 on Days 1, 22, and 43. | 64 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative decision | 2 | 0 |
| Overall Study | Death | 32 | 15 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Other | 1 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 7 |
Baseline characteristics
| Characteristic | Panitumumab Plus Chemoradiation | Chemoradiotherapy Alone | Total |
|---|---|---|---|
| Age, Continuous | 58.0 Years STANDARD_DEVIATION 8.4 | 56.6 Years STANDARD_DEVIATION 8.8 | 57.4 Years STANDARD_DEVIATION 8.5 |
| Nodal status N+ | 77 Participants | 55 Participants | 132 Participants |
| Nodal status N0 | 12 Participants | 9 Participants | 21 Participants |
| Primary tumor site Oral Cavity/Hypopharynx | 21 Participants | 23 Participants | 44 Participants |
| Primary tumor site Oropharynx/Larynx | 68 Participants | 41 Participants | 109 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 8 Participants | 12 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized White or Caucasian | 82 Participants | 55 Participants | 137 Participants |
| Radiotherapy delivery modality 3D-CRT | 35 Participants | 21 Participants | 56 Participants |
| Radiotherapy delivery modality IMRT | 52 Participants | 42 Participants | 94 Participants |
| Radiotherapy delivery modality Missing | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Female | 13 Participants | 7 Participants | 20 Participants |
| Sex: Female, Male Male | 76 Participants | 57 Participants | 133 Participants |
| Tumor stage T1-3 | 64 Participants | 45 Participants | 109 Participants |
| Tumor stage T4 | 25 Participants | 19 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 87 / 87 | 63 / 63 |
| serious Total, serious adverse events | 37 / 87 | 20 / 63 |
Outcome results
Primary
Local Regional Control Rate at 2 Years
In this study participants were considered to be in local regional control (LRC) if there was no evidence of active disease in the previously affected/irradiated head-and-neck area. LRC could be achieved at any time following completion of treatment unless disease progression in the local-regional area occurred or the participant received subsequent anti-tumor therapy. Local regional control rate is defined as the Kaplan-Meier (KM) estimate of the proportion of participants with local regional control.
Time frame: 2 years
Population: Efficacy Analysis Set (all randomized participants who received at least 1 dose of protocol-specified treatment according to treatment randomization regardless of treatment received.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab Plus Chemoradiation | Local Regional Control Rate at 2 Years | 0.61 proportion of paticipants |
| Chemoradiotherapy Alone | Local Regional Control Rate at 2 Years | 0.68 proportion of paticipants |
95% CI: [-0.23, 0.09]
Secondary
Duration of Local-regional Control
Duration of local regional control is calculated from the first day of any study treatment (radiotherapy, chemotherapy, or panitumumab) administration to the date of first local-regional failure or to death due to any cause (whichever occurs first). Local-regional failure includes persistent disease and local-regional recurrence of disease. Participants who did not meet the criteria for LRC recurrence after achieving a response by the analysis data cutoff date were censored at their last evaluable disease assessment date. Participants who never achieved LRC were considered to have a duration of 0.
Time frame: From first dose up to 37 months
Population: Efficacy Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Chemoradiation | Duration of Local-regional Control | 33.7 months |
| Chemoradiotherapy Alone | Duration of Local-regional Control | NA months |
p-value: 0.310695% CI: [0.767, 2.299]Regression, Cox
Secondary
Local Regional Control Rate at 6 Months and 12 Months
Participants were considered to be in local regional control (LRC) if there was no evidence of active disease in the previously affected/irradiated head-and-neck area. LRC could be achieved at any time following completion of treatment unless disease progression in the local-regional area occurred or the participant received subsequent anti-tumor therapy. Local regional control rate is defined as the Kaplan-Meier (KM) estimate of the proportion of participants with local regional control.
Time frame: 6 months and 12 months
Population: Efficacy Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panitumumab Plus Chemoradiation | Local Regional Control Rate at 6 Months and 12 Months | 6 months | 0.70 proportion of paticipants |
| Panitumumab Plus Chemoradiation | Local Regional Control Rate at 6 Months and 12 Months | 12 months | 0.66 proportion of paticipants |
| Chemoradiotherapy Alone | Local Regional Control Rate at 6 Months and 12 Months | 6 months | 0.73 proportion of paticipants |
| Chemoradiotherapy Alone | Local Regional Control Rate at 6 Months and 12 Months | 12 months | 0.70 proportion of paticipants |
Comparison: Difference between treatment groups at 6 months95% CI: [-0.18, 0.12]
Comparison: Difference between treatment groups at 12 months95% CI: [-1.09, 0.12]
Secondary
Overall Survival
Survival time is defined as time from the first day of any study treatment to date of death. Participants who had not died by the cutoff date were censored at their last contact date.
Time frame: From first dose date up to 37 months
Population: Efficacy Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Chemoradiation | Overall Survival | 33.7 months |
| Chemoradiotherapy Alone | Overall Survival | NA months |
p-value: 0.122395% CI: [0.877, 3.019]Regression, Cox
Secondary
Percentage of Participants With a Complete Response at 6 Months
Response assessment based on central review of scans using a a modification of the WHO criteria, during the first 6 months. Complete Response is defined as the disappearance of all index and non-index lesions and no new lesions.
Time frame: 6 months
Population: Evaluable for Central Tumor Response Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab Plus Chemoradiation | Percentage of Participants With a Complete Response at 6 Months | 20.69 percentage of participants |
| Chemoradiotherapy Alone | Percentage of Participants With a Complete Response at 6 Months | 19.35 percentage of participants |
p-value: 195% CI: [0.448, 2.712]Regression, Logistic
95% CI: [-13.23, 14.71]
Secondary
Percentage of Participants With an Objective Response at 6 Months
Objective response by 6 months is defined as a complete response or partial response based on central review of scans using a a modification of the WHO criteria during the first 6 months. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the size of index lesions with no progression in non-index lesions, or the disappearance of all index lesions and persistence of 1 or more non-index lesions not qualifying for either CR or progressive disease and no new lesions.
Time frame: 6 months
Population: Evaluable for Central Tumor Response Analysis Set: the subset of participants in the Efficacy Analysis Set with at least one bi-dimensionally measurable lesion at baseline using a modified version of the WHO criteria per blinded central review.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab Plus Chemoradiation | Percentage of Participants With an Objective Response at 6 Months | 71.26 percentage of participants |
| Chemoradiotherapy Alone | Percentage of Participants With an Objective Response at 6 Months | 82.26 percentage of participants |
p-value: 0.173795% CI: [0.217, 1.262]Regression, Logistic
95% CI: [-24.56, 4.14]
Secondary
Progression-Free Survival
Progression-free survival time is defined as time from the first day of any study treatment to date of first progresive disease using a modified version of the World Health Organization (WHO) criteria or death. Progressive Disease is defined as at least a 25% increase in the size of index lesions or unequivocal progression of existing non-index lesions or the presence of one or more new lesions. Participants not meeting these criteria by the cutoff date were censored at their last evaluable disease assessment date.
Time frame: From first dose date to 37 months
Population: Efficacy Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Chemoradiation | Progression-Free Survival | NA months |
| Chemoradiotherapy Alone | Progression-Free Survival | NA months |
p-value: 0.606995% CI: [0.675, 1.961]Regression, Cox