Back to resultsEMD 1201081 + 5-FU + Cisplatin + Cetuximab in Subjects With Recurrent / Metastatic Squamous Cell Carcinoma of the Head and Neck
Primary Purpose
Squamous Cell Carcinoma of the Head and Neck
Status
Terminated
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
EMD 1201081 + 5-FU + Cisplatin + Cetuximab
EMD 1201081 + 5-FU + Cisplatin + Cetuximab
Sponsored by
About this trial
This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck focused on measuring Safety, tolerability, maximum tolerated dose of EMD 1201081, TLR9 agonists, squamous cell carcinoma of the head and neck, First line subjects, recurrent/metastatic
Eligibility 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.
Sites / Locations
- Clinical Research Unit and Pharmacology Lab EA 3035 Institut Claudius Regaud
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm 1 (Part 1)
Arm 2 (Expansion cohorts -Part 2 and Part 2a)
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
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.
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Secondary Outcome Measures
Number of subjects with best overall response
Pharmacokinetic parameters: Cmax, Tmax and AUC (0-t)
Full Information
NCT ID
NCT01360827
First Posted
May 24, 2011
Last Updated
June 16, 2014
Sponsor
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT01360827
Brief Title
EMD 1201081 + 5-FU + Cisplatin + Cetuximab in Subjects With Recurrent / Metastatic Squamous Cell Carcinoma of the Head and Neck
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Terminated
Why Stopped
Study terminated due to potential safety concerns in combination with platinum-based therapies
Study Start Date
August 2010 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 (Part 1)
Arm Type
Experimental
Arm Title
Arm 2 (Expansion cohorts -Part 2 and Part 2a)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
EMD 1201081 + 5-FU + Cisplatin + Cetuximab
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
EMD 1201081 + 5-FU + Cisplatin + Cetuximab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum-tolerated-dose (MTD) at 0.16 mg/kg cohort size testing
Description
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.
Time Frame
3 weeks
Title
Maximum-tolerated-dose (MTD) at 0.32 mg/kg cohort size testing
Description
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.
Time Frame
3 weeks
Title
Maximum-tolerated-dose (MTD) at 0.48 mg/kg cohort size testing
Description
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.
Time Frame
3 weeks
Title
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 Measure Information:
Title
Number of subjects with best overall response
Time Frame
8 months
Title
Pharmacokinetic parameters: Cmax, Tmax and AUC (0-t)
Time Frame
Days 1, 8 and 15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr. Jean-Pierre Delord
Organizational Affiliation
Clinical Research Unit and Pharmacology Lab EA 3035, Institut Claudius Regaud, Toulouse, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Research Unit and Pharmacology Lab EA 3035 Institut Claudius Regaud
City
Toulouse
Country
France
12. IPD Sharing Statement
Learn more about this trial
EMD 1201081 + 5-FU + Cisplatin + Cetuximab in Subjects With Recurrent / Metastatic Squamous Cell Carcinoma of the Head and Neck
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