Recurrent and/or Metastatic Head and Neck Cancer
Conditions
Keywords
Squamous Cell Carcinoma, Epidermal Growth Factor, Epidermal Growth Factor Receptor, SCCHN, Metastatic Head and Neck Cancer, EGFr, Head and Neck Cancer, Recurrent Head and Neck Cancer
Brief summary
The purpose of this study is to determine the treatment effect of Panitumumab in combination with chemotherapy versus chemotherapy alone as first line therapy for metastatic and/or recurrent squamous cell carcinoma of the head and neck.
Interventions
DRUGARM 2
Subjects will receive Cisplatin plus 5FU
DRUGARM 1
Subjects will receive Panitumumab plus cisplatin and 5FU
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
* Man or woman at least 18 years old. * Histologically or cytologically confirmed metastatic and/or recurrent squamous cell carcinoma (or its variants) of the head and neck. * Diagnosis of metastatic disease and/or recurrent disease following locoregional therapy and determined to be incurable by surgery or radiotherapy. * Subjects who have received radiation as primary therapy are eligible if locoregional recurrence is in the field of radiation and has occurred ≥6 months after the completion of radiation therapy. Subjects whose locoregional recurrence is solely outside the field of radiation are eligible if the recurrence has occurred ≥ 3 months after the completion of radiation therapy. * Measurable and non-measurable disease. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion criteria
* History or known presence of Central Nervous System (CNS) metastases. * History of another primary cancer, except: curatively treated in situ cervical cancer, or curatively resected non-melanoma skin cancer, or other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 2 years before randomization. * Nasopharyngeal carcinoma. * Prior systemic treatment for metastatic and/or recurrent SCCHN * Prior cisplatin containing induction chemotherapy followed by cisplatin containing chemoradiotherapy * Prior anti-EGFr (Epidermal growth factor receptor) antibody therapy or treatment with small molecule EGFr inhibitors * Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) less than or equal to 1 year prior to randomization. History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan. * Symptomatic peripheral neuropathy grade ≥ 2 based on the CTCAE v3.0 * Grade ≥ 3 hearing loss based on the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Auditory/Ear (Hearing \[without monitoring program\])
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Upto 56 months | Time from randomization to death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Every 6 weeks until disease progression, up to 56 months | An objective tumor response of complete or partial response per modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 that was confirmed no less than 28 days after the criteria for response were first met. Complete response = disappearance of all target lesions and partial response = ≥30% reduction in lesion size. |
| Duration of Response | Every 6 weeks until disease progression, up to 56 months | Time from the first confirmed objective response of complete or partial response (that is subsequently confirmed at least 28 days later) to disease progression using a modified version of the RECIST v1.0 (see protocol Appendix H). |
| Time to Progression | Every 6 weeks until disease progression, up to 56 months | Time from randomization date to date of disease progression using a modified version of the RECIST 1.0 (see protocol Appendix H) |
| Time to Response | Every 6 weeks until disease progression, upto 56 months | Time from randomization date to the first confirmed objective response of complete or partial response (that is subsequently confirmed at least 28 days later) using a modified version of the RECIST v1.0. |
| Progression Free Survival | Every 6 weeks until disease progression or deaths, upto 56 months | Time from randomization date to date of disease progression using a modified version of the RECIST v1.0 or death. |
Participant flow
Recruitment details
Subjects were enrolled from 25 May 2007 to 10 March 2009.
Participants by arm
| Arm | Count |
|---|---|
| Panitumumab Plus Chemotherapy Consists of Panitumumab plus Cisplatin and 5-FU | 327 |
| Chemotherapy Alone Consists of Cisplatin and 5-FU | 330 |
| Total | 657 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 14 | 15 |
| Overall Study | Ongoing | 60 | 47 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Withdrawal by Subject | 10 | 25 |
Baseline characteristics
| Characteristic | Panitumumab Plus Chemotherapy | Total | Chemotherapy Alone |
|---|---|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 8.5 | 58.1 years STANDARD_DEVIATION 8.2 | 58.6 years STANDARD_DEVIATION 7.8 |
| ECOG perfomance score, 0/1/2 0 | 98 subjects | 196 subjects | 98 subjects |
| ECOG perfomance score, 0/1/2 1 | 227 subjects | 455 subjects | 228 subjects |
| ECOG perfomance score, 0/1/2 2 | 2 subjects | 6 subjects | 4 subjects |
| Previously treated with chemotherapy and/or radiotherapy, Yes/No No | 60 subjects | 127 subjects | 67 subjects |
| Previously treated with chemotherapy and/or radiotherapy, Yes/No Yes | 267 subjects | 530 subjects | 263 subjects |
| Primary tumor site, oropharynx&larynx/oral cavity&hypopharynx Oral cavity and hypopharynx | 141 subjects | 280 subjects | 139 subjects |
| Primary tumor site, oropharynx&larynx/oral cavity&hypopharynx Oropharynx and larynx | 186 subjects | 377 subjects | 191 subjects |
| Race/Ethnicity, Customized Aborigine | 1 subjects | 1 subjects | 0 subjects |
| Race/Ethnicity, Customized Asian | 25 subjects | 55 subjects | 30 subjects |
| Race/Ethnicity, Customized Black or African American | 4 subjects | 6 subjects | 2 subjects |
| Race/Ethnicity, Customized Hispanic or Latino | 13 subjects | 25 subjects | 12 subjects |
| Race/Ethnicity, Customized Japanese | 13 subjects | 20 subjects | 7 subjects |
| Race/Ethnicity, Customized Other | 3 subjects | 9 subjects | 6 subjects |
| Race/Ethnicity, Customized Unknown/Missing | 0 subjects | 2 subjects | 2 subjects |
| Race/Ethnicity, Customized White or Caucasian | 268 subjects | 539 subjects | 271 subjects |
| Sex: Female, Male Female | 44 Participants | 87 Participants | 43 Participants |
| Sex: Female, Male Male | 283 Participants | 570 Participants | 287 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 311 / 325 | 301 / 325 |
| serious Total, serious adverse events | 157 / 325 | 139 / 325 |
Outcome results
Primary
Overall Survival
Time from randomization to death
Time frame: Upto 56 months
Population: Intention to treat (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Chemotherapy | Overall Survival | 11.1 months |
| Chemotherapy Alone | Overall Survival | 9.0 months |
p-value: 0.140395% CI: [0.729, 1.046]Log Rank
Secondary
Duration of Response
Time from the first confirmed objective response of complete or partial response (that is subsequently confirmed at least 28 days later) to disease progression using a modified version of the RECIST v1.0 (see protocol Appendix H).
Time frame: Every 6 weeks until disease progression, up to 56 months
Population: Included only those subjects with a confirmed complete or partial response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Chemotherapy | Duration of Response | 5.6 months |
| Chemotherapy Alone | Duration of Response | 5.7 months |
Secondary
Overall Response Rate
An objective tumor response of complete or partial response per modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 that was confirmed no less than 28 days after the criteria for response were first met. Complete response = disappearance of all target lesions and partial response = ≥30% reduction in lesion size.
Time frame: Every 6 weeks until disease progression, up to 56 months
Population: The subset of subjects in the ITT analysis set with at least one baseline uni-dimensionally measurable lesion using a modified version of the RECIST v1.0 (see protocol Appendix H)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab Plus Chemotherapy | Overall Response Rate | 101 subjects |
| Chemotherapy Alone | Overall Response Rate | 73 subjects |
95% CI: [3.13, 18.68]
95% CI: [1.15, 2.44]
Secondary
Progression Free Survival
Time from randomization date to date of disease progression using a modified version of the RECIST v1.0 or death.
Time frame: Every 6 weeks until disease progression or deaths, upto 56 months
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Chemotherapy | Progression Free Survival | 5.8 months |
| Chemotherapy Alone | Progression Free Survival | 4.6 months |
95% CI: [0.659, 0.922]
Secondary
Time to Progression
Time from randomization date to date of disease progression using a modified version of the RECIST 1.0 (see protocol Appendix H)
Time frame: Every 6 weeks until disease progression, up to 56 months
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Chemotherapy | Time to Progression | 6.8 months |
| Chemotherapy Alone | Time to Progression | 5.6 months |
Secondary
Time to Response
Time from randomization date to the first confirmed objective response of complete or partial response (that is subsequently confirmed at least 28 days later) using a modified version of the RECIST v1.0.
Time frame: Every 6 weeks until disease progression, upto 56 months
Population: Included only those subjects with a confirmed complete response or partial response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus Chemotherapy | Time to Response | 1.4 months |
| Chemotherapy Alone | Time to Response | 1.5 months |