EMD 1201081 + 5-FU + Cisplatin + Cetuximab in Subjects With Recurrent / Metastatic Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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The primary purpose of this trial is to assess the safety and tolerability of EMD 1201081, a novel immunomodulatory agent that is an agonist of TLR9, in combination with 5-FU/cisplatin and cetuximab in first line treatment of patients with recurrent/metastatic squamous cell carcinoma of the head and neck, and to determine the maximum tolerated dose (MTD) among the dose levels.

Official Title
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Phase Ib Trial of Multiple-ascending Doses of EMD 1201081 in Combination With 5-FU/Cisplatin and Cetuximab in First-line Subjects With Recurrent/ Metastatic Squamous Cell Carcinoma of the Head and Neck

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: EMD 1201081 + 5-FU + Cisplatin + Cetuximab
* Drug: EMD 1201081 + 5-FU + Cisplatin + Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck (SCCHN). Recurrent and/or metastatic SCCHN, not suitable for local therapy. At least 1 measurable lesion either by computerized tomography (CT) scan or magnetic resonance imaging (MRI) (according to RECIST 1.0). Karnofsky performance status (KPS) of ≥ 70 / Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at trial entry. Exclusion Criteria: Prior systemic chemotherapy, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 2 months prior to trial entry. Nasopharyngeal carcinoma. Medical history of diagnosed interstitial lung disease. Known hypersensitivity against any of the components of the trial treatment. Previous treatment with experimental or non-approved epidermal growth factor receptor (EGFR) targeting therapy or experimental or nonapproved EGFR signal transduction inhibitors (prior treatment with cetuximab is allowed). Relevant cardiovascular co-morbidities. Concomitant chronic systemic immune therapy, or hormonal therapy as cancer therapy, steroid use ≥ 10 mg prednisone equivalent. Known human immunodeficiency virus (HIV) positivity, active hepatitis C, or active hepatitis B.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 (Part 1)<br> | Drug: EMD 1201081 + 5-FU + Cisplatin + Cetuximab<br>* 3-6 subjects per cohort will receive EMD 1201081 as a weekly subcutaneous injection on Days 1, 8, and 15 in 3-week cycles at dose levels of 0.16, 0.32, and 0.48mg/kg, respectively until progression of disease, unacceptable toxicity, or subject refusal to continue in the trial. EMD 1201081 will always be given after (within 1 hour) completion of the cetuximab infusion and before the start of chemotherapy.<br>|
| Experimental: Arm 2 (Expansion cohorts -Part 2 and Part 2a)<br> | Drug: EMD 1201081 + 5-FU + Cisplatin + Cetuximab<br>* Part 2 seeks to enroll 12 subjects at the MTD of EMD 1201081 in combination with 5-FU/cisplatin + cetuximab; furthermore, an additional 3 to 6 subjects for a total of 9 subjects will be accrued at the 0.16 mg/kg low dose level in Part 2a once the Part 1 0.16 mg/kg dose cohort has been accrued and it is deemed safe to proceed to the 0.32 mg/kg dose cohort. EMD 1201081 will always be given after (within 1 hour) completion of the cetuximab infusion and before the start of chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum-tolerated-dose (MTD) at 0.16 mg/kg cohort size testing | Occurrence of treatment-related dose-limiting toxicity during the first cycle (3 weeks) of treatment in subjects treated with multi-ascending doses of EMD 1201081 in combination with 5-FU/cisplatin + cetuximab. | 3 weeks | 
| Maximum-tolerated-dose (MTD) at 0.32 mg/kg cohort size testing | Occurrence of treatment-related dose-limiting toxicity during the first cycle (3 weeks) of treatment in subjects treated with multi-ascending doses of EMD 1201081 in combination with 5-FU/cisplatin + cetuximab. | 3 weeks | 
| Maximum-tolerated-dose (MTD) at 0.48 mg/kg cohort size testing | Occurrence of treatment-related dose-limiting toxicity during the first cycle (3 weeks) of treatment in subjects treated with multi-ascending doses of EMD 1201081 in combination with 5-FU/cisplatin + cetuximab. | 3 weeks | 
| Number of subjects with adverse events (AEs) and serious adverse events (SAEs) |  | Baseline up to 49 days after last study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with best overall response |  | 8 months | 
| Pharmacokinetic parameters: Cmax, Tmax and AUC (0-t) |  | Days 1, 8 and 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, tolerability, maximum tolerated dose of EMD 1201081, TLR9 agonists, squamous cell carcinoma of the head and neck, First line subjects, recurrent/metastatic