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

NCT01360827 | Terminated Phase 1

• 1 other identifier: EMR 200068-007
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

Safety; tolerability; maximum tolerated dose of EMD 1201081; TLR9 agonists; squamous cell carcinoma of the head and neck; First line subjects; recurrent/metastatic

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• Number of subjects with best overall response

  8 months

• Pharmacokinetic parameters: Cmax, Tmax and AUC (0-t)

  Days 1, 8 and 15

Study Arms (2)

Arm 1 (Part 1)

EXPERIMENTAL

Drug: EMD 1201081 + 5-FU + Cisplatin + Cetuximab

Arm 2 (Expansion cohorts -Part 2 and Part 2a)

EXPERIMENTAL

Drug: EMD 1201081 + 5-FU + Cisplatin + Cetuximab

Interventions

EMD 1201081 + 5-FU + Cisplatin + Cetuximab DRUG

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.

Arm 1 (Part 1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Clinical Research Unit and Pharmacology Lab EA 3035 Institut Claudius Regaud

Toulouse, France

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Neoplasm Metastasis

Interventions

IMO-2055; Fluorouracil; Cisplatin; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dr. Jean-Pierre Delord

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2011
• First Posted: May 26, 2011
• Study Start: August 1, 2010
• Primary Completion: April 1, 2011
• Last Updated: June 17, 2014

Record last verified: 2014-06

Locations

FR (1)