Chemotherapy With Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Squamous Cell Head and Neck Carcinoma Clinical Trial

Official title:

Phase II Study of Cetuximab, Docetaxel and Cisplatin as First-line Treatment in Patients With Metastatic or Recurrent Head and Neck Squamous Cell Carcinomas - GORTEC2008-03 TPEx

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01289522
• Other study ID #: GORTEC2008-03TPex
• Secondary ID: 2008-004869-25
• Status: Active, not recruiting
• Phase: Phase 2
• First received: February 1, 2011
• Last updated: January 2, 2014
• Start date: September 2009
• Est. completion date: January 2014

Study information

• Verified date: January 2014
• Source: Groupe Oncologie Radiotherapie Tete et Cou
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

PURPOSE: Cetuximab with platinum and 5FU is now the standard combination as first-line treatment in patients with metastatic or recurrent Head and Neck squamous cell carcinomas. Cetuximab and taxane combinations have demonstrated promising activity in Head and Neck cancer. This phase II trial is studying new cetuximab, docetaxel and cisplatin combination named TPEx as first-line treatment in this setting.

Description:

OBJECTIVES:

Primary

• To determine the efficacy of TPEx combination in patients with head and neck cancer in term of objective response rate (RECIST, see statistical consideration) Secondary

• To assess toxicities of TPEx combination

• Determine the efficacy of TPEx combination in patients with head and neck cancer: Best Overall Response , progression-free survival and survival.

• Translational research objective:To better understand the mechanisms of chemoresistance and to identify biomarkers by the analysis of the tumor biopsies (RNA, gene expression profile) and protein profile (plasma samples). Exploratory analyses.

OUTLINE: This is an open-label phase II, multicenter study. Patients receive four cycles of chemotherapy comprising cetuximab IV plus docetaxel IV over 1 hour and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of the fourth cycle of chemotherapy, patients receive a maintenance therapy with cetuximab every 2 weeks. Treatment will be continued until disease progression or unacceptable toxicities according to the patient or the investigator. Tumor check-up will be performed every 6 weeks. This study will allow translational research with blood sample and biopsies at baseline before any treatment, during the treatment with TPEx combination (week 6).,After completion of study treatment, patients are followed every 2 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 54
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Histologically proven squamous cell carcinoma of the oral cavity, larynx, oropharynx or hypopharynx

• Recurrent disease, incurable disease as determined by surgery or radiation, or metastatic disease

• Measurable or evaluable disease

• Age > 18 years and <= 70 years

• WHO performance status 0 or 1

• Absolute neutrophil count > 1,500/mm3

• Platelets > 150,000/mm3

• Total Bilirubin <= institutional upper limit of normal

• Aspartate aminotransferase < 1.5 X institutional upper limit of normal

• Alanine aminotransferase < 1.5 X institutional upper limit of normal

• Alkaline phosphatase < 2.5 X institutional upper limit of normal

• creatinine clearance > 60 mL/min

• Signed informed consent

• Women of child-bearing potential and men must be willing and able practice adequate contraception prior to study entry and for the duration of study treatment

Exclusion Criteria:

• Previous chemotherapy. Chemotherapy given as part of initial curative therapy and completed more than 6 months before inclusion is allowed

• Previous treatment with total doses of cisplatin > 300 mg/ m2

• Patients must not have any co-existing disease that would preclude cisplatin administration, such as peripheral neuropathy or renal failure

• Surgery (excluding biopsy) or radiotherapy within 4 weeks prior to study entry

• Nasopharyngeal carcinoma, or cancer of sinusal cavities

• Active infection including tuberculosis or HIV positive patient

• Other malignancy within last 5 years except for non-melanoma skin cancer

• No other investigational agent within 30 days prior to study entry

• No other concurrent chemotherapy, immunotherapy, antitumor hormonal therapy (excluding contraceptives and replacement steroids), radiotherapy, or experimental medications

• No prior anti EGFR therapy

• No known brain metastases

• Uncontrolled intercurrent illness that would prevent delivery of protocol therapy

• Patients with a prior history of basal cell carcinoma of the skin or in situ carcinoma of the cervix must have been curatively treated and must have remained disease free for 5 years post diagnosis

• No history of hypersensitivity reaction to drugs on study

• No unstable angina or myocardial infarction within the past 12 months

• No symptomatic congestive heart failure or New York Heart Association (NYHA) class II-IV heart disease

• No serious uncontrolled cardiac arrhythmia

• No other prior or concomitant squamous cell carcinoma

• No other prior or concomitant cancer, except curatively treated basal carcinoma of the skin or in situ cervical cancer, for which the patient has been curatively treated and remains disease-free for the past 5 years

• Patient is pregnant or lactating

• Patients must not have any co-existing condition that would preclude full compliance with the study

Study Design

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Neoplasm Metastasis
• Recurrent or Metastatic Disease
• Squamous Cell Head and Neck Carcinoma

Intervention

Biological:
• cetuximab IV
Cetuximab 400 mg/m² over 120 minutes on day 1 of cycle 1 only. Cetuximab dose will be 250 mg/m² IV over 60 minutes weekly on subsequent administrations during the four cycles of chemotherapy. Cetuximab dose will be 500mg/m2 IV every 2 weeks during the maintenance therapy. Drug: Cisplatin IV : 75 mg/m2 intravenous every 3 weeks for 4 cycles Drug: Docetaxel IV : 75 mg/m2 intravenous every 3 weeks for 4 cycles G-CSF support with lenograstim 150 microg./m2/day is delivered after each cycle of chemotherapy.

Other:
• Biopsies
No intervention, only biopsy for translational project.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires	Bruxelles
Belgium	Clinique Sainte Elisabeth	Namur
Belgium	Clinique universitaire de Mont Godinne UCL	Yvoir
France	Hôpital Saint André	Bordeaux
France	Centre Jean Perrin,	Clermont-Ferrand
France	Centre G-F Leclerc	Dijon
France	Centre Hospitalier de la Dracénie	Draguignan
France	Centre Hospitalier de Bretagne Sud	Lorient
France	Centre Léon Bérard	Lyon
France	Hôpital de la Timone	Marseille
France	Centre Henri Becquerel	Rouen
France	Hôpital Foch	Suresnes
France	CHU Bretonneau	Tours
France	Institut Gustave Roussy	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
Groupe Oncologie Radiotherapie Tete et Cou	Gustave Roussy, Cancer Campus, Grand Paris

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	objective tumor response rate	The objective tumor response rate is evaluated every 6 weeks according to RECIST criteria	12 weeks (after completion of the fourth cycle of chemotherapy)	No
Secondary	Grade 1 to 5 toxicity	All grade 1 to 5 toxicity are registered during treatment. Patients have weekly clinical and biological examination.	24 weeks (average)	Yes
Secondary	best overall response	Tumor response is evaluated every 6 weeks according to RECIST criteria	12 weeks	No
Secondary	progression-free survival		1 year	No
Secondary	overall survival		1 year	No
Secondary	biomarkers		two years	No

External Links

•   GORTEC