Patritumab With Cetuximab and a Platinum Agent for Squamous Cell Carcinoma (Cancer) of the Head and Neck (SCCHN )

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized, Placebo-controlled, Double-blind Phase 2 Study of Patritumab (U3-1287) in Combination With Cetuximab Plus Platinum-based Therapy in First Line Setting in Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Drug: Patritumab
* Drug: Cetuximab
* Drug: Cisplatin
* Drug: Carboplatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patritumab<br>All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin) | Drug: Patritumab<br>* 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<br>* Other names: U3-1287;Drug: Cetuximab<br>* Cetuximab 400 mg/mg/m^2 IV loading dose, followed by 250 mg/m^2 weekly<br>Drug: Cisplatin<br>* Cisplatin at 100 mg/m^2 IV infused over 1 hour, every three weeks up to a maximum of 6 cycles<br>* Other names: Platinum-based therapy;Drug: Carboplatin<br>* Carboplatin IV over 30 to 60 minutes, every 3 weeks for a maximum of 6 cycles<br>* Other names: Platinum-based therapy;|
| Placebo Comparator: Placebo<br>All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin) | Drug: Cetuximab<br>* Cetuximab 400 mg/mg/m^2 IV loading dose, followed by 250 mg/m^2 weekly<br>Drug: Cisplatin<br>* Cisplatin at 100 mg/m^2 IV infused over 1 hour, every three weeks up to a maximum of 6 cycles<br>* Other names: Platinum-based therapy;Drug: Carboplatin<br>* Carboplatin IV over 30 to 60 minutes, every 3 weeks for a maximum of 6 cycles<br>* Other names: Platinum-based therapy;Drug: Placebo<br>* Placebo to match patritumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | from Day 0 to end of active study (study termination) - within 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Overall Survival | Overall survival (OS) is defined as the time from the date of randomization to death due to any cause | at approximately 25 months | 
| 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) | at approximately 22 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous cell cancer of the head and neck, Squamous cell carcinoma, Head and neck cancer, Neoplasms by site