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

Squamous Cell Carcinoma of the Head and Neck Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01360827
• Other study ID #: EMR 200068-007
• Status: Terminated
• Phase: Phase 1
• First received: May 24, 2011
• Last updated: June 16, 2014
• Start date: August 2010

Study information

• Verified date: June 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsGermany: Federal Institute for Drugs and Medical Devices (BfArM)France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Squamous Cell Carcinoma of the Head and Neck

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	Clinical Research Unit and Pharmacology Lab EA 3035 Institut Claudius Regaud	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	Number of subjects with adverse events (AEs) and serious adverse events (SAEs)		Baseline up to 49 days after last study drug administration	Yes
Secondary	Number of subjects with best overall response		8 months	No
Secondary	Pharmacokinetic parameters: Cmax, Tmax and AUC (0-t)		Days 1, 8 and 15	No