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

This study has been terminated.
(Study terminated due to potential safety concerns in combination with platinum-based therapies)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01360827
First Posted: May 26, 2011
Last Update Posted: June 17, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck KGaA
  Purpose
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.

Condition Intervention Phase
Squamous Cell Carcinoma of the Head and Neck Drug: EMD 1201081 + 5-FU + Cisplatin + Cetuximab Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Maximum-tolerated-dose (MTD) at 0.16 mg/kg cohort size testing [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Baseline up to 49 days after last study drug administration ]

Secondary Outcome Measures:
  • Number of subjects with best overall response [ Time Frame: 8 months ]
  • Pharmacokinetic parameters: Cmax, Tmax and AUC (0-t) [ Time Frame: Days 1, 8 and 15 ]

Enrollment: 13
Study Start Date: August 2010
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 (Part 1) Drug: EMD 1201081 + 5-FU + Cisplatin + Cetuximab
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.
Experimental: Arm 2 (Expansion cohorts -Part 2 and Part 2a) Drug: EMD 1201081 + 5-FU + Cisplatin + Cetuximab
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.

  Eligibility

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01360827


Locations
France
Clinical Research Unit and Pharmacology Lab EA 3035 Institut Claudius Regaud
Toulouse, France
Sponsors and Collaborators
Merck KGaA
Investigators
Principal Investigator: Dr. Jean-Pierre Delord Clinical Research Unit and Pharmacology Lab EA 3035, Institut Claudius Regaud, Toulouse, France
  More Information

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01360827     History of Changes
Other Study ID Numbers: EMR 200068-007
First Submitted: May 24, 2011
First Posted: May 26, 2011
Last Update Posted: June 17, 2014
Last Verified: June 2014

Keywords provided by Merck KGaA:
Safety
tolerability
maximum tolerated dose of EMD 1201081
TLR9 agonists
squamous cell carcinoma of the head and neck
First line subjects
recurrent/metastatic

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cisplatin
Cetuximab
Fluorouracil
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs