Head and Neck Neoplasms
Conditions
Keywords
Squamous cell cancer of the head and neck, Squamous cell carcinoma, Head and neck cancer, Neoplasms by site
Brief summary
This study will test an investigational study drug called patritumab. It is a 'randomized study' which means participants have an equal chance of being assigned to receive the experimental medication (patritumab) or a substance that looks like the experimental product, but is not (placebo). Patritumab may work when combined with other medications that are approved for the treatment of head and neck cancer. They are called cetuximab, cisplatin or carboplatin. All participants will receive the other medications approved for treatment of head and neck cancer, even if they do not receive the experimental product.
Detailed description
Main objective of the trial: The main objective of the trial is to evaluate progression-free survival (PFS) in the heregulin (HRG) high expression population from subjects treated with patritumab + cetuximab + platinum-based therapy compared to placebo + cetuximab + platinum-based therapy.
Interventions
DRUGPatritumab
Patritumab initial loading dose is 18 mg/kg IV over 60 minutes followed by a maintenance dose of 9 mg/kg IV over 60 minutes (± 10 minutes) every three weeks
DRUGCetuximab
Cetuximab 400 mg/mg/m\^2 IV loading dose, followed by 250 mg/m\^2 weekly
DRUGCisplatin
Cisplatin at 100 mg/m\^2 IV infused over 1 hour, every three weeks up to a maximum of 6 cycles
DRUGCarboplatin
Carboplatin IV over 30 to 60 minutes, every 3 weeks for a maximum of 6 cycles
DRUGPlacebo
Placebo to match patritumab
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has histologically confirmed recurrent disease or metastatic SCCHN tumor and/or from its lymph nodal metastases originating from the oral cavity, oropharynx, hypopharynx, and larynx * Has or be willing to provide tumor tissue for testing * Has measurable disease per Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 * Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Has adequate hematological function per protocol * Has adequate renal function per protocol * Has adequate hepatic function per protocol * Agrees to use effective contraception while on the study and for 6-months after the end of the study * Provides written informed consent(s)
Exclusion criteria
* Has left ventricular ejection fraction (LVEF) \<50% * Had prior epidermal growth factor receptor (EGFR) targeted regimen * Had prior anti-human epidermal growth factor receptor 3 (anti-HER3) therapy * Had prior chemotherapy for recurrent/metastatic disease * Had anti-cancer therapy between biopsy and submission of sample * Has history of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for ≥ 2 years * Has known history of brain metastases or active brain metastases * Has uncontrolled hypertension * Has clinically significant electrocardiograph (ECG) findings * Had myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure, unstable angina, or arrhythmia requiring medication * Had platinum-containing drug therapy with radiotherapy less than 6 months before study drug treatment * Had therapeutic or palliative radiation therapy or major surgery within 4 weeks before study drug treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) in the Heregulin (HRG)-High Expression Population | from Day 0 to end of active study (study termination) - within 12 months | PFS is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever comes first. Median PFS is from Kaplan-Meier analysis. Confidence interval (CI) for median was computed using Brookmeyer-Crowley method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | at approximately 25 months | Overall survival (OS) is defined as the time from the date of randomization to death due to any cause |
| Percentage of Participants With Best Overall Response | at approximately 22 months | Best overall response rate (ORR) is defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) |
Countries
Belgium, France, Germany, Hungary, Poland, Romania, United Kingdom
Participant flow
Pre-assignment details
Of 125 screened, 87 patients from 8 countries were randomized into treatment groups
Participants by arm
| Arm | Count |
|---|---|
| Patritumab All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin) | 44 |
| Placebo All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin) | 43 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse event, non-fatal | 7 | 2 |
| Overall Study | Clinical progression | 3 | 6 |
| Overall Study | Death | 3 | 3 |
| Overall Study | Patient Request | 1 | 1 |
| Overall Study | Radiologic(al) progression | 23 | 23 |
| Overall Study | Reason not provided | 1 | 0 |
| Overall Study | Study terminated by sponsor | 6 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Patritumab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 57.3 years STANDARD_DEVIATION 9.18 | 61.0 years STANDARD_DEVIATION 9.19 | 59.1 years STANDARD_DEVIATION 9.33 |
| Age, Customized 18-64 Years | 32 Participants | 27 Participants | 59 Participants |
| Age, Customized 65-84 Years | 12 Participants | 16 Participants | 28 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0=Fully active | 19 Participants | 22 Participants | 41 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1=Restricted in Physically Strenuous Activity | 25 Participants | 20 Participants | 45 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2=Ambulatory and Capable of All Self-Care | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 6 Participants | 6 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 37 Participants | 37 Participants | 74 Participants |
| Region of Enrollment Belgium | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment France | 9 Participants | 12 Participants | 21 Participants |
| Region of Enrollment Germany | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Hungary | 20 Participants | 19 Participants | 39 Participants |
| Region of Enrollment Poland | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Romania | 1 Participants | 3 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 9 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 36 Participants | 36 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 24 / 44 | 20 / 43 |
| other Total, other adverse events | 44 / 44 | 42 / 43 |
| serious Total, serious adverse events | 19 / 44 | 16 / 43 |
Outcome results
Primary
Progression Free Survival (PFS) in the Heregulin (HRG)-High Expression Population
PFS is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever comes first. Median PFS is from Kaplan-Meier analysis. Confidence interval (CI) for median was computed using Brookmeyer-Crowley method.
Time frame: from Day 0 to end of active study (study termination) - within 12 months
Population: Participants in the heregulin-high expression population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patritumab | Progression Free Survival (PFS) in the Heregulin (HRG)-High Expression Population | 5.56 months |
| Placebo | Progression Free Survival (PFS) in the Heregulin (HRG)-High Expression Population | 5.56 months |
Comparison: Heregulin-high population - Patritumab vs Placebop-value: 0.834295% CI: [0.4856, 1.7778]Log Rank
Secondary
Median Overall Survival
Overall survival (OS) is defined as the time from the date of randomization to death due to any cause
Time frame: at approximately 25 months
Population: The trial terminated before sufficient data were collected for this analysis (at approximately 12 months which is prior to the time point for this analysis).
Secondary
Percentage of Participants With Best Overall Response
Best overall response rate (ORR) is defined as the percentage of participants with Complete Response (CR) or Partial Response (PR)
Time frame: at approximately 22 months
Population: The trial terminated before sufficient data were collected for this analysis (at approximately 12 months which is prior to the time point for this analysis).