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:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01360827
First received: May 24, 2011
Last updated: June 16, 2014
Last verified: June 2014
  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
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of subjects with best overall response [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters: Cmax, Tmax and AUC (0-t) [ Time Frame: Days 1, 8 and 15 ] [ Designated as safety issue: No ]

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01360827     History of Changes
Other Study ID Numbers: EMR 200068-007
Study First Received: May 24, 2011
Last Updated: June 16, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices (BfArM)
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cetuximab
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 16, 2014