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

Phase 1

Terminated

• Conditions: Squamous Cell Carcinoma of the Head and Neck
• Interventions: Drug: EMD 1201081 + 5-FU + Cisplatin + Cetuximab

• Registration Number: NCT01360827
• Lead Sponsor: Merck KGaA, Darmstadt, Germany

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08
• Primary Completion: 2011-04
• Study First Submitted: 2011-05-24
• Study First Submitted QC: 2011-05-25
• Study First Posted: 2011-05-26
• Status Verified: 2014-06
• Last Update Submitted: 2014-06-16
• Last Update Posted: 2014-06-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 13

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1 (Part 1)	EMD 1201081 + 5-FU + Cisplatin + Cetuximab	-
Arm 2 (Expansion cohorts -Part 2 and Part 2a)	EMD 1201081 + 5-FU + Cisplatin + Cetuximab	-

Primary Outcome Measures

Name	Time	Method
Maximum-tolerated-dose (MTD) at 0.16 mg/kg cohort size testing	3 weeks	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.
Maximum-tolerated-dose (MTD) at 0.32 mg/kg cohort size testing	3 weeks	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.
Maximum-tolerated-dose (MTD) at 0.48 mg/kg cohort size testing	3 weeks	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.
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

Name	Time	Method
Number of subjects with best overall response	8 months
Pharmacokinetic parameters: Cmax, Tmax and AUC (0-t)	Days 1, 8 and 15

Trial Locations

Locations (1)

Clinical Research Unit and Pharmacology Lab EA 3035 Institut Claudius Regaud; 🇫🇷 Toulouse, France