Clinical trial NCT01289522: Chemotherapy With Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer
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 - GORTEC 2008-03 TPEx
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Cell Head and Neck Carcinoma
Recurrent or Metastatic Disease
Keywords: Squamous cell carcinoma of the head and neck
recurrent or metastatic
first line chemotherapy
cetuximab
docetaxel
cisplatin
antineoplastic agents
First Line Palliative Treatment
Lead sponsor: Groupe Oncologie Radiotherapie Tete et Cou
Sponsor class: OTHER
Collaborators: name: Gustave Roussy, Cancer Campus, Grand Paris
First posted: 2011-02-03
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective Tumor Response Rate
timeFrame: 12 weeks (after completion of the 4th cycle of chemotherapy)
Secondary outcomes:
measure: Grade 1 to 5 Toxicity
timeFrame: 24 weeks (average)
measure: Best Overall Response
timeFrame: 12 weeks
measure: Progression-free Survival
timeFrame: 1 year
measure: Overall Survival
timeFrame: 1 year
measure: Biomarkers
timeFrame: two years
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires
city: Namur
country: Belgium
facility: Clinique Sainte Elisabeth
city: Yvoir
country: Belgium
facility: Clinique universitaire de Mont Godinne UCL
city: Bordeaux
country: France
facility: Hôpital Saint André
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin,
city: Dijon
country: France
facility: Centre G-F Leclerc
city: Draguignan
country: France
facility: Centre Hospitalier de la Dracénie
city: Lorient
country: France
facility: Centre Hospitalier de Bretagne Sud
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hôpital de la Timone
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Suresnes
country: France
facility: Hôpital Foch
city: Tours
country: France
facility: CHU Bretonneau
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: GORTEC
name: Joel GUIGAY
role: STUDY_CHAIR
References:
citation: Guigay J, Fayette J, Dillies AF, Sire C, Kerger JN, Tennevet I, Machiels JP, Zanetta S, Pointreau Y, Bozec Le Moal L, Henry S, Schilf A, Bourhis J. Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. Ann Oncol. 2015 Sep;26(9):1941-1947. doi: 10.1093/annonc/mdv268. Epub 2015 Jun 24.