Metastatic or Recurrent Squamous Cell Carcinoma of Head and Neck
Conditions
Keywords
SCCHNC, Metastatic, Recurrent
Brief summary
This is a randomized, open-label, 2-arm, controlled, phase 2, multi-center, estimation clinical trial of docetaxel and cisplatin combination chemotherapy with and without panitumumab in the first-line treatment of subjects with metastatic or recurrent head and neck cancer, as well as a cross-over second-line panitumumab monotherapy of subjects who fail the chemotherapy only arm. This study will be conducted in the United States. Approximately 150 subjects with histologically or cytologically confirmed metastatic and/or recurrent SCCHN.
Interventions
DRUGCisplatin
chemotherapy arm
DRUGPanitumumab
experimental arm
DRUGDocetaxel
chemotherapy arm
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed metastatic and/or recurrent Squamous Cell Carcinoma of Head and Neck (SCCHN) determined to be incurable by surgery and/or radiation therapy. * Measurable disease by CT scan * Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 * Age: 18 years or older * Adequate hematologic, renal, metabolic, hepatic & thyroid function
Exclusion criteria
* Prior systemic treatment for metastatic and/or recurrent SCCHN * CNS metastases, or nasopharyngeal carcinoma * History of interstitial lung disease * History of another primary cancer * Any co-morbid disease that would increase risk of toxicity * Active infection requiring systemic treatment * Prior anti-Epidermal Growth Factor receptor (anti-EGFr) antibody therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) During the First-line Treatment Phase | Every 6 weeks until disease progression or death, up to 67 months | The time from the date of randomization to the date of first disease progression determined by the investigators per modified RECIST v1.0, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever is later) during the first-line treatment phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) During the First-line Treatment Phase | Every 6 weeks until disease progression or death, up to 67 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter (SLD) of target lesions from baseline; Overall Response (OR) = CR + PR. An overall response of CR or PR must be confirmed at least 4 weeks after the criteria for response are first met. ORR is the percentage of subjects with an overall response among the analysis population. |
| Rate of Disease Control (RDC) During the First-line Treatment Phase | Every 6 weeks until disease progression or death, up to 67 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter (SLD) of target lesions from baseline; Disease Progression (PD), \>=20% increase in the SLD of target lesions from nadir; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. An overall response of CR or PR must be confirmed at least 4 weeks after the criteria for response are first met. A best overall response of SD requires a visit response of SD or better no earlier than 35 days after randomization. RCD is the percentage of subjects with a best overall response of CR, PR or SD among the analysis population. |
| Duration of Response (DOR) During the First-line Treatment Phase | Every 6 weeks until disease progression or death, up to 67 months | Calculated only for the subset of subjects who have an overall response of CR or PR while on first-line treatment phase (subsequently confirmed at least 4 weeks thereafter), and is defined as time from the first CR or PR to the first observed disease progression by a modified RECIST v1.0. Subjects not meeting the criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date. |
| Time to Response (TTR) During the First-line Treatment Phase | Every 6 weeks until disease progression or death, up to 67 months | Time from the date of randomization to the first CR or PR during first line treatment phase (subsequently confirmed at least 4 weeks thereafter) |
| Overall Survival (OS) for the Second-line Treatment | Until death, up to 57 months | Time from the first dose of panitumumab monotherapy to the date of death during the entire study |
| Overall Survival (OS) for the First-line Treatment | Until death, up to 67 months | Time from the date of randomization to the date of death during the entire study |
| Progression Free Survival (PFS) During the Second-line Treatment Phase | Every 6 weeks until disease progression or death, up to 57 months | The time from the first dose of panitumumab monotherapy to the date of first disease progression determined by the investigators per modified RECIST v1.0, or death within 60 days after the last evaluable tumor assessment or the second-line first dose date (whichever is later) during the second-line treatment phase. |
| Overall Response Rate (ORR) During the Second-line Treatment Phase | Every 6 weeks until disease progression or death, up to 57 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter (SLD) of target lesions from baseline; Overall Response (OR) = CR + PR. An overall response of CR or PR must be confirmed at least 4 weeks after the criteria for response are first met. ORR is the percentage of subjects with an overall response among the analysis population. |
| Rate of Disease Control (RDC) During the Second-line Treatment Phase | Every 6 weeks until disease progression or death, up to 57 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter (SLD) of target lesions from baseline; Disease Progression (PD), \>=20% increase in the SLD of target lesions from nadir; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. An overall response of CR or PR must be confirmed at least 4 weeks after the criteria for response are first met. A best overall response of SD requires a visit response of SD or better no earlier than 35 days after the first dose date in second-line treatment. RCD is the percentage of subjects with a best overall response of CR, PR or SD among the analysis population. |
| Duration of Response (DOR) During the Second-line Treatment Phase | Every 6 weeks until disease progression or death, up to 57 months | Time from the first CR or PR to the first observed disease progression by a modified RECIST v1.0. Subjects not meeting the criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date. |
| Time to Response (TTR) During the Second-line Treatment Phase | Every 6 weeks until disease progression or death, up to 57 months | Time from the first dose of panitumumab monotherapy to the first CR or PR during second-line treatment phase (subsequently confirmed at least 4 weeks thereafter) |
Countries
Austria, Belgium, Czechia, France, Lithuania, Puerto Rico, Slovakia, Spain, United States
Participant flow
Recruitment details
Subjects were enrolled from 29 January 2007 to 1 September 2010.
Pre-assignment details
The planned number of subjects to enroll was 110. The actual number of subjects enrolled was 113.
Participants by arm
| Arm | Count |
|---|---|
| Panitumumab Plus Chemotherapy Panitumumab + Docetaxel + Cisplatin, experiment | 56 |
| Chemotherapy Alone Docetaxel + Cisplatin, control | 57 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First-line Treatment Phase | Ended follow-up prior to analysis | 1 | 1 |
| First-line Treatment Phase | Lack of Efficacy | 0 | 2 |
| First-line Treatment Phase | Lost to Follow-up | 1 | 0 |
| First-line Treatment Phase | Ongoing | 1 | 0 |
| First-line Treatment Phase | Protocol Violation | 0 | 1 |
| First-line Treatment Phase | Withdrawal by Subject | 2 | 4 |
| Second-line Treatment Phase | Ended follow-up prior to analysis | 0 | 1 |
| Second-line Treatment Phase | Ongoing | 0 | 1 |
| Second-line Treatment Phase | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Panitumumab Plus Chemotherapy | Chemotherapy Alone | Total |
|---|---|---|---|
| Age, Continuous | 58.2 Years STANDARD_DEVIATION 8.6 | 58.9 Years STANDARD_DEVIATION 7.4 | 58.6 Years STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 9 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Male | 47 Participants | 52 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 54 / 56 | 53 / 55 |
| serious Total, serious adverse events | 34 / 56 | 27 / 55 |
Outcome results
Primary
Progression Free Survival (PFS) During the First-line Treatment Phase
The time from the date of randomization to the date of first disease progression determined by the investigators per modified RECIST v1.0, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever is later) during the first-line treatment phase.
Time frame: Every 6 weeks until disease progression or death, up to 67 months
Population: All randomized participants \< 70 years of age who provide informed consent and receive at least one dose of first-line treatment (chemotherapy and/or panitumumab)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Chemotherapy | Progression Free Survival (PFS) During the First-line Treatment Phase | 6.9 Months |
| Chemotherapy Alone | Progression Free Survival (PFS) During the First-line Treatment Phase | 5.5 Months |
p-value: 0.05195% CI: [0.395, 1.002]Regression, Cox
p-value: 0.048Log Rank
Secondary
Duration of Response (DOR) During the First-line Treatment Phase
Calculated only for the subset of subjects who have an overall response of CR or PR while on first-line treatment phase (subsequently confirmed at least 4 weeks thereafter), and is defined as time from the first CR or PR to the first observed disease progression by a modified RECIST v1.0. Subjects not meeting the criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date.
Time frame: Every 6 weeks until disease progression or death, up to 67 months
Population: All randomized participants \< 70 years of age who provide informed consent and receive at least one dose of first-line treatment (chemotherapy and/or panitumumab), with at least one uni-dimensionally measurable lesion at baseline using a modified RECIST v1.0 per investigators' review and objective response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Chemotherapy | Duration of Response (DOR) During the First-line Treatment Phase | 8.0 Months |
| Chemotherapy Alone | Duration of Response (DOR) During the First-line Treatment Phase | 5.1 Months |
Secondary
Duration of Response (DOR) During the Second-line Treatment Phase
Time from the first CR or PR to the first observed disease progression by a modified RECIST v1.0. Subjects not meeting the criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date.
Time frame: Every 6 weeks until disease progression or death, up to 57 months
Population: Subjects who are randomized to docetaxel and cisplatin chemotherapy alone treatment for their first-line treatment and treated subsequently with at least 1 dose of second-line panitumumab monotherapy, with at least one uni-dimensionally measurable lesion at baseline using a modified RECIST v1.0 per investigators' review and objective response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy Alone | Duration of Response (DOR) During the Second-line Treatment Phase | NA Months |
Secondary
Overall Response Rate (ORR) During the First-line Treatment Phase
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter (SLD) of target lesions from baseline; Overall Response (OR) = CR + PR. An overall response of CR or PR must be confirmed at least 4 weeks after the criteria for response are first met. ORR is the percentage of subjects with an overall response among the analysis population.
Time frame: Every 6 weeks until disease progression or death, up to 67 months
Population: all randomized subjects \< 70 years of age who provide informed consent and receive at least one dose of first-line treatment (chemotherapy and/or panitumumab), with at least one uni-dimensionally measurable lesion at baseline using a modified RECIST v1.0 per investigators' review
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Panitumumab Plus Chemotherapy | Overall Response Rate (ORR) During the First-line Treatment Phase | 44.23 Percentage of Participants |
| Chemotherapy Alone | Overall Response Rate (ORR) During the First-line Treatment Phase | 37.25 Percentage of Participants |
95% CI: [-11.67, 24.12]
95% CI: [0.57, 3.33]
Secondary
Overall Response Rate (ORR) During the Second-line Treatment Phase
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter (SLD) of target lesions from baseline; Overall Response (OR) = CR + PR. An overall response of CR or PR must be confirmed at least 4 weeks after the criteria for response are first met. ORR is the percentage of subjects with an overall response among the analysis population.
Time frame: Every 6 weeks until disease progression or death, up to 57 months
Population: Subjects who are randomized to docetaxel and cisplatin chemotherapy alone treatment for their first-line treatment and treated subsequently with at least 1 dose of second-line panitumumab monotherapy
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chemotherapy Alone | Overall Response Rate (ORR) During the Second-line Treatment Phase | 13.33 Percentage of Participants |
Secondary
Overall Survival (OS) for the First-line Treatment
Time from the date of randomization to the date of death during the entire study
Time frame: Until death, up to 67 months
Population: All randomized participants \< 70 years of age who provide informed consent and receive at least one dose of first-line treatment (chemotherapy and/or panitumumab)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Chemotherapy | Overall Survival (OS) for the First-line Treatment | 12.9 Months |
| Chemotherapy Alone | Overall Survival (OS) for the First-line Treatment | 13.8 Months |
p-value: 0.66395% CI: [0.709, 1.717]Regression, Cox
p-value: 0.666Log Rank
Secondary
Overall Survival (OS) for the Second-line Treatment
Time from the first dose of panitumumab monotherapy to the date of death during the entire study
Time frame: Until death, up to 57 months
Population: Subjects who are randomized to docetaxel and cisplatin chemotherapy alone treatment for their first-line treatment and treated subsequently with at least 1 dose of second-line panitumumab monotherapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy Alone | Overall Survival (OS) for the Second-line Treatment | 8.5 Months |
Secondary
Progression Free Survival (PFS) During the Second-line Treatment Phase
The time from the first dose of panitumumab monotherapy to the date of first disease progression determined by the investigators per modified RECIST v1.0, or death within 60 days after the last evaluable tumor assessment or the second-line first dose date (whichever is later) during the second-line treatment phase.
Time frame: Every 6 weeks until disease progression or death, up to 57 months
Population: Subjects who are randomized to docetaxel and cisplatin chemotherapy alone treatment for their first-line treatment and treated subsequently with at least 1 dose of second-line panitumumab monotherapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy Alone | Progression Free Survival (PFS) During the Second-line Treatment Phase | 4.2 Months |
Secondary
Rate of Disease Control (RDC) During the First-line Treatment Phase
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter (SLD) of target lesions from baseline; Disease Progression (PD), \>=20% increase in the SLD of target lesions from nadir; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. An overall response of CR or PR must be confirmed at least 4 weeks after the criteria for response are first met. A best overall response of SD requires a visit response of SD or better no earlier than 35 days after randomization. RCD is the percentage of subjects with a best overall response of CR, PR or SD among the analysis population.
Time frame: Every 6 weeks until disease progression or death, up to 67 months
Population: all randomized subjects \< 70 years of age who provide informed consent and receive at least one dose of first-line treatment (chemotherapy and/or panitumumab), with at least one uni-dimensionally measurable lesion at baseline using a modified RECIST v1.0 per investigators' review
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Panitumumab Plus Chemotherapy | Rate of Disease Control (RDC) During the First-line Treatment Phase | 80.77 Percentage of Participants |
| Chemotherapy Alone | Rate of Disease Control (RDC) During the First-line Treatment Phase | 72.55 Percentage of Participants |
95% CI: [-8.29, 23.85]
95% CI: [0.62, 5.26]
Secondary
Rate of Disease Control (RDC) During the Second-line Treatment Phase
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter (SLD) of target lesions from baseline; Disease Progression (PD), \>=20% increase in the SLD of target lesions from nadir; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. An overall response of CR or PR must be confirmed at least 4 weeks after the criteria for response are first met. A best overall response of SD requires a visit response of SD or better no earlier than 35 days after the first dose date in second-line treatment. RCD is the percentage of subjects with a best overall response of CR, PR or SD among the analysis population.
Time frame: Every 6 weeks until disease progression or death, up to 57 months
Population: Subjects who are randomized to docetaxel and cisplatin chemotherapy alone treatment for their first-line treatment and treated subsequently with at least 1 dose of second-line panitumumab monotherapy
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chemotherapy Alone | Rate of Disease Control (RDC) During the Second-line Treatment Phase | 53.33 Percentage of Participants |
Secondary
Time to Response (TTR) During the First-line Treatment Phase
Time from the date of randomization to the first CR or PR during first line treatment phase (subsequently confirmed at least 4 weeks thereafter)
Time frame: Every 6 weeks until disease progression or death, up to 67 months
Population: All randomized participants \< 70 years of age who provide informed consent and receive at least one dose of first-line treatment (chemotherapy and/or panitumumab), with at least one uni-dimensionally measurable lesion at baseline using a modified RECIST v1.0 per investigators' review and objective response
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panitumumab Plus Chemotherapy | Time to Response (TTR) During the First-line Treatment Phase | 8.8 Weeks | Standard Deviation 3.9 |
| Chemotherapy Alone | Time to Response (TTR) During the First-line Treatment Phase | 10.6 Weeks | Standard Deviation 6.1 |
Secondary
Time to Response (TTR) During the Second-line Treatment Phase
Time from the first dose of panitumumab monotherapy to the first CR or PR during second-line treatment phase (subsequently confirmed at least 4 weeks thereafter)
Time frame: Every 6 weeks until disease progression or death, up to 57 months
Population: Subjects who are randomized to docetaxel and cisplatin chemotherapy alone treatment for their first-line treatment and treated subsequently with at least 1 dose of second-line panitumumab monotherapy, with at least one uni-dimensionally measurable lesion at baseline using a modified RECIST v1.0 per investigators' review and objective response
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chemotherapy Alone | Time to Response (TTR) During the Second-line Treatment Phase | 10.6 Weeks | Standard Deviation 5.6 |