Cancer, Head and Neck Cancer, Oncology, Squamous Cell Carcinoma
Conditions
Keywords
head and neck, squamous cell carcinoma, radiotherapy, chemoradiotherapy, panitumumab, locally advanced head & neck cancer, EGFr, epidermal growth factor receptor, SCCHN, locally advanced SCCHN, HNC, epidermal growth factor
Brief summary
The purpose of this study is to estimate, with pre-specified precision, the difference in local-regional control (LRC) rate at 2 years in subjects receiving chemoradiotherapy (CRT) or panitumumab plus radiotherapy (PRT) as first line treatment for locally advanced squamous cell carcinoma for the head and neck (SCCHN). A formal hypothesis will not be tested in this trial; however, the treatment arm difference in LRC rates at 2 years will be estimated.
Detailed description
Primary Objective: To estimate, with pre-specified precision, the difference in local-regional control (LRC) rate at 2 years in subjects receiving chemoradiotherapy (CRT) or panitumumab plus radiotherapy (PRT) as first line treatment for locally advanced squamous cell carcinoma for the head and neck (SCCHN). Secondary Objectives: To estimate the difference between 2 treatment regimens (CRT vs PRT) on other measures of clinical benefit, including LRC, overall response rate (ORR), progression-free survival (PFS), overall survival (OS); and safety. Tertiary Objectives: To estimate the difference in health-related quality of life (HRQoL) and performance status in subjects receiving PRT or CRT. Exploratory Objectives: To investigate potential biomarker development based on assessment of blood and tumor and the proposed mechanism of actions of study drugs. In addition, to investigate the effect of genetic variation in cancer genes and drug target genes on SCCHN and subject response to study drugs (separate informed consent required). Hypothesis: A formal hypothesis will not be tested in this trial; however, the treatment arm difference in LRC rates at 2 years will be estimated. Study Design: This is a phase 2, open-label, randomized, multicenter study. Eligible subjects will be randomized in a 2:3 ratio to either of the following regimens: Arm 1 CRT: * Accelerated fractionation RT: 70 to 72 Gy - delivered over 6 to 6.5 weeks * Cisplatin: 100 mg/m2 (given on days 1 and 22 of RT) or Arm 2 PRT: * Accelerated fractionation RT: 70 to 72 Gy - delivered over 6 to 6.5 weeks * Panitumumab: 9.0 mg/kg Q3W (given on days 1, 22, and 43 of RT)
Interventions
DRUGPanitumumab
Arm 2 consists of panitmumab plus RT
DRUGCisplatin
Cisplatin
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
Histologically or cytologically confirmed SCC of the oral cavity, oropharynx, hypopharynx or larynx Stage III or Stage IVa-b (M0) disease according to the American Joint Committee on Cancer staging manual 6th edition (locally advanced) ECOG performance status of 0 or 1 Bidimensionally measurable disease \>/= 10 mm in at least 1 dimension
Exclusion criteria
NO Primary tumor of the nasopharynx, sinuses, salivary gland, or skin NO Subjects requiring prophylactic tracheostomy NO Prior (or concomitant) malignancy (except non-melanomatous skin cancer or in situ cervical cancer), other than the study disease (SCCHN), unless treated with curative intent with no evidence of disease for \>/= 3 years NO Prior treatment for locally advanced SSCHN NO Prior surgery for SCCHN (except nodal sampling or biopsy for study disease) NO Major surgery \</= 28 days before randomization or minor surgery \</= 14 days before randomization with the exception of feeding tube placement, dental extractions, central venous catheter placement, biopsies and nodal sampling
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local Regional Control Rate at 2 Years | from study day 1 to 2 years | Kaplan-Meier estimate of Local regional control rate at 2 years. Local regional control rate will be measured according to the investigator's assessment of disease status based on all available data (ie, from clinical examination, radiologic assessments, pathology reports, and autopsy reports). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Local Regional Control | maximum follow up time 46.2 months | Time from study day 1 to the date of first local-regional failure or to death due to any cause (whichever occurs first) |
| Progression-free Survival | maximum follow up time 46.2 months | Time from first dose date till disease progression or death |
| Overall Survival | maximum follow up time 46.2 months | Time from first dose date to death |
| ORR by 6 Months - Central | From randomization to 6 months | ORR is Objective Response Rate. Tumor assessments are based on central review of scans uisng a modification of the WHO criteria. Complete or partial response is considered as objective response. |
| CRR by 6 Months - Central | From randomization till 6 months | CRR is Complete Response Rate. Tumor assessments are based on central review of scans uisng a modification of the WHO criteria. Complete Response (CR) is defined as disappearance of all index lesions. |
Participant flow
Recruitment details
152 subjects were enrolled with 90 subjects randomized to panitumumab plus radiotherapy arm, and 62 subjects randomized to chemoradiotherapy arm.
Participants by arm
| Arm | Count |
|---|---|
| Panitumumab Plus Radiotherpy Consists of Panitumumab and Radiotherpy | 90 |
| Chemoradiotherapy Cisplatin (100 mg/m2 day 1 and day 22) plus Accelerated Fractionation Radiotherapy | 62 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative decision | 3 | 2 |
| Overall Study | Death | 38 | 18 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Panitumumab Plus Radiotherpy | Chemoradiotherapy | Total |
|---|---|---|---|
| Age, Continuous | 56.9 Years STANDARD_DEVIATION 8.3 | 57.4 Years STANDARD_DEVIATION 7.9 | 57.1 Years STANDARD_DEVIATION 8.1 |
| Nodal Status N+ | 79 Participants | 55 Participants | 134 Participants |
| Nodal Status N0 | 11 Participants | 7 Participants | 18 Participants |
| Primary Tumor Site Oral Cavity/Hypopharynx | 24 Participants | 18 Participants | 42 Participants |
| Primary Tumor Site Oropharynx/Larynx | 66 Participants | 44 Participants | 110 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 00 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 88 Participants | 60 Participants | 148 Participants |
| Radiotherapy Delivery Modality 3D-CRT | 41 Participants | 29 Participants | 70 Participants |
| Radiotherapy Delivery Modality IMRT | 49 Participants | 32 Participants | 81 Participants |
| Radiotherapy Delivery Modality Missing | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 18 Participants | 7 Participants | 25 Participants |
| Sex: Female, Male Male | 72 Participants | 55 Participants | 127 Participants |
| Tumor Stage T1-3 | 58 Participants | 39 Participants | 97 Participants |
| Tumor Stage T4 | 32 Participants | 23 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 88 / 89 | 61 / 62 |
| serious Total, serious adverse events | 30 / 89 | 25 / 62 |
Outcome results
Primary
Local Regional Control Rate at 2 Years
Kaplan-Meier estimate of Local regional control rate at 2 years. Local regional control rate will be measured according to the investigator's assessment of disease status based on all available data (ie, from clinical examination, radiologic assessments, pathology reports, and autopsy reports).
Time frame: from study day 1 to 2 years
Population: Efficacy Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab Plus Radiotherapy | Local Regional Control Rate at 2 Years | 0.51 Proportion of Participants |
| Chemoradiotherapy | Local Regional Control Rate at 2 Years | 0.61 Proportion of Participants |
95% CI: [-0.26, 0.07]
Secondary
CRR by 6 Months - Central
CRR is Complete Response Rate. Tumor assessments are based on central review of scans uisng a modification of the WHO criteria. Complete Response (CR) is defined as disappearance of all index lesions.
Time frame: From randomization till 6 months
Population: Evaluable for Central Tumor Response Analysis Set: the subset of subjects in the Efficacy Analysis Set with at least one bi-dimensionally measurable leasion at baseline using a modification of the WHO criteria per blinded central review.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab Plus Radiotherapy | CRR by 6 Months - Central | 0.144 Proportion of Participants |
| Chemoradiotherapy | CRR by 6 Months - Central | 0.117 Proportion of Participants |
p-value: 0.80795% CI: [0.438, 4.043]Regression, Logistic
95% CI: [-0.103, 0.141]
Secondary
Duration of Local Regional Control
Time from study day 1 to the date of first local-regional failure or to death due to any cause (whichever occurs first)
Time frame: maximum follow up time 46.2 months
Population: Efficacy Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Radiotherapy | Duration of Local Regional Control | 25.1 months |
| Chemoradiotherapy | Duration of Local Regional Control | NA months |
p-value: 0.060195% CI: [0.98, 2.656]Regression, Cox
Secondary
ORR by 6 Months - Central
ORR is Objective Response Rate. Tumor assessments are based on central review of scans uisng a modification of the WHO criteria. Complete or partial response is considered as objective response.
Time frame: From randomization to 6 months
Population: Evaluable for Central Tumor Response Analysis Set: the subset of subjects in the Efficacy Analysis Set with at least one bi-dimensionally measurable leasion at baseline using a modification of the WHO criteria per blinded central review.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab Plus Radiotherapy | ORR by 6 Months - Central | 0.722 Proporation of Participants |
| Chemoradiotherapy | ORR by 6 Months - Central | 0.767 Proporation of Participants |
p-value: 0.574495% CI: [0.342, 1.785]Regression, Logistic
95% CI: [-0.187, 0.112]
Secondary
Overall Survival
Time from first dose date to death
Time frame: maximum follow up time 46.2 months
Population: Efficacy Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Radiotherapy | Overall Survival | 41.7 months |
| Chemoradiotherapy | Overall Survival | NA months |
p-value: 0.103995% CI: [0.909, 2.793]Regression, Cox
Secondary
Progression-free Survival
Time from first dose date till disease progression or death
Time frame: maximum follow up time 46.2 months
Population: Efficacy analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Radiotherapy | Progression-free Survival | 17.3 months |
| Chemoradiotherapy | Progression-free Survival | NA months |
p-value: 0.025995% CI: [1.068, 2.806]Regression, Cox