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

Phase 2

Completed

Conditions: Squamous Cell Head and Neck Carcinoma
Recurrent or Metastatic Disease

Interventions: Biological: cetuximab IV
Other: Biopsies

Registration Number: NCT01289522

Lead Sponsor: Groupe Oncologie Radiotherapie Tete et Cou

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

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

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
cetuximab	Biopsies	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
cetuximab	cetuximab IV	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

Primary Outcome Measures

Name	Time	Method
Objective Tumor Response Rate	12 weeks (after completion of the 4th cycle of chemotherapy)	The objective tumor response rate is evaluated every 6 weeks according to RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT-scan or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.

Secondary Outcome Measures

Name	Time	Method
Biomarkers	two years
Overall Survival	1 year
Grade 1 to 5 Toxicity	24 weeks (average)	All grade 1 to 5 toxicity are registered during treatment. Patients have weekly clinical and biological examination.
Best Overall Response	12 weeks	Tumor response is evaluated every 6 weeks according to RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions, Stable Disease (SD); Best overall Response = CR + PR + SD.
Progression-free Survival	1 year

Trial Locations

Locations (14): Cliniques Universitaires
🇧🇪
Bruxelles, Belgium
Centre Léon Bérard
🇫🇷
Lyon, France
Hôpital Saint André
🇫🇷
Bordeaux, France
Hôpital de la Timone
🇫🇷
Marseille, France
Clinique universitaire de Mont Godinne UCL
🇧🇪
Yvoir, Belgium
Centre Hospitalier de la Dracénie
🇫🇷
Draguignan, France
Centre Henri Becquerel
🇫🇷
Rouen, France
Hôpital Foch
🇫🇷
Suresnes, France
Clinique Sainte Elisabeth
🇧🇪
Namur, Belgium
Centre Jean Perrin,
🇫🇷
Clermont-Ferrand, France
Centre G-F Leclerc
🇫🇷
Dijon, France
Centre Hospitalier de Bretagne Sud
🇫🇷
Lorient, France
CHU Bretonneau
🇫🇷
Tours, France
Institut Gustave Roussy
🇫🇷
Villejuif, France