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

June 16, 2014 updated by: Merck KGaA, Darmstadt, Germany

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
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.
Experimental: Arm 2 (Expansion cohorts -Part 2 and Part 2a)
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.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
3 weeks
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.
3 weeks
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.
3 weeks
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Time Frame: Baseline up to 49 days after last study drug administration
Baseline up to 49 days after last study drug administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Number of subjects with best overall response
Time Frame: 8 months
8 months
Pharmacokinetic parameters: Cmax, Tmax and AUC (0-t)
Time Frame: Days 1, 8 and 15
Days 1, 8 and 15

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck KGaA, Darmstadt, Germany

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dr. Jean-Pierre Delord, Clinical Research Unit and Pharmacology Lab EA 3035, Institut Claudius Regaud, Toulouse, France

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 24, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 25, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 26, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 17, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 16, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EMR 200068-007

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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