Cancer, Carcinoma, Head and Neck Cancer, Metastases, Metastatic Cancer, Metastatic or Recurrent Squamous Cell Carcinoma of Head and Neck, Oncology, Squamous Cell Carcinoma, Tumors
Conditions
Brief summary
To estimate the effect of second-line panitumumab monotherapy on objective response in patients with metastatic or recurrent squamous cell carcinoma of head and neck (SCCHN).
Interventions
DRUGPanitumumab
Panitumumab was administered over a 1 hour intraveneous (IV) infusion at a dose of 9 mg/kg every 21 days.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed squamous cell carcinoma of head and neck (SCCHN) of oropharynx, oral cavity, hypopharynx, or larynx with at least 1 measurable lesion using computed tomography (CT) or magnetic resonance imaging (MRI) scan * Diagnosis of recurrent disease determined to be incurable by surgery or radiotherapy * Karnofsky Performance Status (KPS) score ≥ 60% at screening * Men or women age ≥18 years * Adequate hematologic, electrolyte and hepatic functions and negative pregnancy test
Exclusion criteria
* Subject received \> 1 chemotherapy regimen for the treatment of metastatic or recurrent disease * Concomitant chemotherapy for recurrent disease administered solely for the purpose of radiation sensitization during re-irradiation will not be counted towards this chemotherapy regimen * Nasopharyngeal carcinoma, salivary gland and primary skin SCCHN, or symptomatic central nervous system (CNS) metastases * History of interstitial lung disease, significant cardiovascular disease, or another primary cancer * Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic hepatitis B infection * Known allergy or hypersensitivity to any component of panitumumab * Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (eg, panitumumab, cetuximab) or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib) for recurrent or metastatic disease with the following exceptions: * Prior EGFr inhibitor therapy is allowed if received as part of prior multimodality treatment (eg, as radiation sensitizer) and completed \> 24 weeks prior to randomization * Subjects who received no more than one dose of cetuximab and discontinued prior to progression due to documented severe infusion reaction are eligible. * Significant thromboembolic event ≤ 8 weeks prior to enrollment * Subjects not recovered from all previous acute radiotherapy-related toxicities * History of severe skin disorder that in the opinion of the investigator may interfere with study conduct * History of any medical, or psychiatric condition, or laboratory abnormality that may interfere with the interpretation of study results * Subject is currently in a clinical trial ≤ 30 days prior to enrollment * Subjects requiring use of immunosuppressive agents however corticosteroids are allowed * Man or woman of child-bearing potential who do not consent to use adequate contraceptive precautions during the course of the study * Female subject who is pregnant or breast-feeding * Subject requiring major surgery using general/spinal anesthesia ≤ 28 days prior to enrollment, or minor surgery ≤ 14 days prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | From first dose of study drug until the data cut-off date of 16 December 2010. Median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks). | Assessments are based on investigator's review of scans using a modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Objective response rate was defined as the percentage of participants with a best tumor response of complete response (CR) or partial response (PR) prior to initiation of subsequent anti-cancer therapy. CR or PR was confirmed no less than 28 days after the criteria for response were first met. CR: Disappearance of all target lesions, non-target lesions and no new lesions. PR: At least a 30% decrease in the size of target lesions and no progression of existing non-target lesions (defined as an increase in lesion size of ≥ 20%) and no new lesions, or, the disappearance of all target lesions and the persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease (PD) and no new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks) | Duration of response was defined as the time from first confirmed CR or PR to the earliest date of disease progression per a modified version of the RECIST criteria (version 1.0). Participants not meeting the criteria for progression by the analysis data cut-off date were censored at the date of last evaluable disease assessment. Duration of response was analyzed using the Kaplan-Meier method. PD: At least a 20% increase in the size of target lesions, or an increase of 20% or greater of non-target lesions and the lesion(s) measure ≥ 10 mm in one dimension at the time of progression, or any new lesions. |
| Rate of Disease Control | From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks). | Rate of disease control was defined as the percentage of participants with CR, PR, or stable disease (SD), as defined by a modified version of the RECIST criteria (version 1.0), prior to initiation of subsequent anti-cancer therapy. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD of target lesions and no progression of non-target lesions and no new lesions, or, if no target lesions were identified at screening, the persistence of one or more non-target lesion(s) not qualifying for either CR or PD. |
| Time to Progression | From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks). | Time to progression was defined as the time from Day 1 to the date of disease progression using a modified version of the RECIST criteria (version 1.0). Participants not meeting the criteria for progression by the analysis data cut-off date were censored at the date of last evaluable disease assessment. Time to progression was analyzed using the Kaplan-Meier method. |
| Time to Response | From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks) | Time to response was defined as the time from Study Day 1 to the first CR or PR that was subsequently confirmed. |
| Overall Survival (OS) | From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks). | Overall Survival was defined as the time from Day 1 to the date of death. For participants who did not die while on study, or were lost to follow-up, survival was censored at the end of study, or the date of last contact (whichever was first). |
| Number of Participants With Adverse Events | The reporting time frame for Adverse Events is from first dose date to 30 days since the last dose date date. The median time frame is 2.4 months. | The severity of each adverse event (AE) was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (where grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening and grade 5=fatal) with the exception of some dermatology/skin AEs that were graded using the CTCAE v3.0 with modifications. Serious AEs include any event that was fatal, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. Treatment-related adverse events (TRAEs) are those for which the investigator considered there to be a reasonable possibility that the event may have been caused by study drug. |
| Progression Free Survival (PFS) | From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks). | PFS was defined as the time from Day 1 to the first date of disease progression, as defined by a modified version of the RECIST criteria (version 1.0), or death due to any cause (whichever comes first). Participants who were alive who did not meet the criteria for progression by the analysis data cut-off date were censored at the date of last evaluable disease assessment. PFS was analyzed using the Kaplan-Meier method. |
Participant flow
Recruitment details
A total of 65 patients with metastatic or recurrent squamous cell carcinoma of the head and neck were screened of whom 52 were enrolled at 22 study centers in North America (20 study centers) and Australia (2 study centers) between October 2007 and December 2009.
Pre-assignment details
Results are reported for the primary analysis with a data cut-off date of 16 December 2010.
Participants by arm
| Arm | Count |
|---|---|
| Panitumumab Participants received panitumumab as an intravenous infusion at a dose of 9 mg/kg every 21 days until disease progression, unacceptable toxicity, withdrawal of consent, death, or end of study. | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 10 |
| Overall Study | Disease Progession | 2 |
| Overall Study | On Treatment at Time of Data Cut-off | 1 |
| Overall Study | Other | 4 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Panitumumab |
|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 8.9 |
| Cancer Stage of Diagnosis Locally recurrent disease without metastases | 11 participants |
| Cancer Stage of Diagnosis Metastatic | 41 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = (Fully Active) | 20 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 = (Restrictive but Ambulatory) | 31 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = (Ambulatory unable to Work) | 1 participants |
| Primary Tumor Site Hypopharynx | 1 participants |
| Primary Tumor Site Larynx | 13 participants |
| Primary Tumor Site Oral Cavity | 20 participants |
| Primary Tumor Site Oropharynx | 18 participants |
| Prior Treatment for Head and neck Cancer Prior chemotherapy | 52 participants |
| Prior Treatment for Head and neck Cancer Prior radiotherapy | 48 participants |
| Prior Treatment for Head and neck Cancer Prior surgery | 46 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants |
| Race/Ethnicity, Customized Other | 1 participants |
| Race/Ethnicity, Customized White or Caucasian | 48 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 50 / 52 |
| serious Total, serious adverse events | 14 / 52 |
Outcome results
Primary
Objective Response Rate
Assessments are based on investigator's review of scans using a modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Objective response rate was defined as the percentage of participants with a best tumor response of complete response (CR) or partial response (PR) prior to initiation of subsequent anti-cancer therapy. CR or PR was confirmed no less than 28 days after the criteria for response were first met. CR: Disappearance of all target lesions, non-target lesions and no new lesions. PR: At least a 30% decrease in the size of target lesions and no progression of existing non-target lesions (defined as an increase in lesion size of ≥ 20%) and no new lesions, or, the disappearance of all target lesions and the persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease (PD) and no new lesions.
Time frame: From first dose of study drug until the data cut-off date of 16 December 2010. Median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks).
Population: Full analysis set (all enrolled participants who received at least 1 dose of panitumumab) with measurable disease at Baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab | Objective Response Rate | 3.9 percentage of participants |
Secondary
Duration of Response
Duration of response was defined as the time from first confirmed CR or PR to the earliest date of disease progression per a modified version of the RECIST criteria (version 1.0). Participants not meeting the criteria for progression by the analysis data cut-off date were censored at the date of last evaluable disease assessment. Duration of response was analyzed using the Kaplan-Meier method. PD: At least a 20% increase in the size of target lesions, or an increase of 20% or greater of non-target lesions and the lesion(s) measure ≥ 10 mm in one dimension at the time of progression, or any new lesions.
Time frame: From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks)
Population: Full analysis set participants with an objective response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Duration of Response | NA months |
Secondary
Number of Participants With Adverse Events
The severity of each adverse event (AE) was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (where grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening and grade 5=fatal) with the exception of some dermatology/skin AEs that were graded using the CTCAE v3.0 with modifications. Serious AEs include any event that was fatal, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. Treatment-related adverse events (TRAEs) are those for which the investigator considered there to be a reasonable possibility that the event may have been caused by study drug.
Time frame: The reporting time frame for Adverse Events is from first dose date to 30 days since the last dose date date. The median time frame is 2.4 months.
Population: Safety analysis set (all enrolled participants who received at least 1 dose of panitumumab)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panitumumab | Number of Participants With Adverse Events | Treatment-related leading to removal from study | 2 participants |
| Panitumumab | Number of Participants With Adverse Events | Any adverse event | 52 participants |
| Panitumumab | Number of Participants With Adverse Events | Worst grade of 3 | 18 participants |
| Panitumumab | Number of Participants With Adverse Events | Worst grade of 4 | 4 participants |
| Panitumumab | Number of Participants With Adverse Events | Worst grade of 5 | 5 participants |
| Panitumumab | Number of Participants With Adverse Events | Serious adverse event | 14 participants |
| Panitumumab | Number of Participants With Adverse Events | Leading to discontinuation of panitumumab | 4 participants |
| Panitumumab | Number of Participants With Adverse Events | Leading to removal from study | 5 participants |
| Panitumumab | Number of Participants With Adverse Events | Treatment-related adverse event | 45 participants |
| Panitumumab | Number of Participants With Adverse Events | Treatment-related worst grade of 3 | 9 participants |
| Panitumumab | Number of Participants With Adverse Events | Treatment-related worst grade of 4 | 1 participants |
| Panitumumab | Number of Participants With Adverse Events | Treatment-related worst grade of 5 | 1 participants |
| Panitumumab | Number of Participants With Adverse Events | Serious treatment-related adverse event | 3 participants |
| Panitumumab | Number of Participants With Adverse Events | TRAE leading to discontinuation of panitumumab | 0 participants |
Secondary
Overall Survival (OS)
Overall Survival was defined as the time from Day 1 to the date of death. For participants who did not die while on study, or were lost to follow-up, survival was censored at the end of study, or the date of last contact (whichever was first).
Time frame: From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks).
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Overall Survival (OS) | 5.1 months |
Secondary
Progression Free Survival (PFS)
PFS was defined as the time from Day 1 to the first date of disease progression, as defined by a modified version of the RECIST criteria (version 1.0), or death due to any cause (whichever comes first). Participants who were alive who did not meet the criteria for progression by the analysis data cut-off date were censored at the date of last evaluable disease assessment. PFS was analyzed using the Kaplan-Meier method.
Time frame: From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks).
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Progression Free Survival (PFS) | 1.4 months |
Secondary
Rate of Disease Control
Rate of disease control was defined as the percentage of participants with CR, PR, or stable disease (SD), as defined by a modified version of the RECIST criteria (version 1.0), prior to initiation of subsequent anti-cancer therapy. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD of target lesions and no progression of non-target lesions and no new lesions, or, if no target lesions were identified at screening, the persistence of one or more non-target lesion(s) not qualifying for either CR or PD.
Time frame: From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks).
Population: Full analysis set with measurable disease at Baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab | Rate of Disease Control | 39.2 percentage of participants |
Secondary
Time to Progression
Time to progression was defined as the time from Day 1 to the date of disease progression using a modified version of the RECIST criteria (version 1.0). Participants not meeting the criteria for progression by the analysis data cut-off date were censored at the date of last evaluable disease assessment. Time to progression was analyzed using the Kaplan-Meier method.
Time frame: From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks).
Population: Full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Time to Progression | 1.4 months |
Secondary
Time to Response
Time to response was defined as the time from Study Day 1 to the first CR or PR that was subsequently confirmed.
Time frame: From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks)
Population: Full analysis set participants with objective responses
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Time to Response | 14.3 weeks |