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

• ClinicalTrials.gov Identifier: NCT01289522
• Recruitment Status: Completed
• First Posted: February 3, 2011
• Results First Posted: April 7, 2017
• Last Update Posted: May 15, 2017
• Sponsor: Groupe Oncologie Radiotherapie Tete et Cou
• Collaborator: Gustave Roussy, Cancer Campus, Grand Paris
• Information provided by (Responsible Party): Groupe Oncologie Radiotherapie Tete et Cou

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Squamous Cell Head and Neck Carcinoma; Recurrent or Metastatic Disease	Biological: cetuximab IV; Other: Biopsies	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: September 2009
• Actual Primary Completion Date: January 2014
• Actual Study Completion Date: January 2014

Arms and Interventions

Arm

Intervention/treatment

Experimental: cetuximab; 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

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.

Outcome Measures

Primary Outcome Measures :

1. Objective Tumor Response Rate [ Time Frame: 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 :

1. Grade 1 to 5 Toxicity [ Time Frame: 24 weeks (average) ]
   All grade 1 to 5 toxicity are registered during treatment. Patients have weekly clinical and biological examination.
2. Best Overall Response [ Time Frame: 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.
3. Progression-free Survival [ Time Frame: 1 year ]
4. Overall Survival [ Time Frame: 1 year ]
5. Biomarkers [ Time Frame: two years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Belgium

Cliniques Universitaires

Bruxelles, Belgium

Clinique Sainte Elisabeth

Namur, Belgium

Clinique universitaire de Mont Godinne UCL

Yvoir, Belgium

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, France

Sponsors and Collaborators

Groupe Oncologie Radiotherapie Tete et Cou

Gustave Roussy, Cancer Campus, Grand Paris

Investigators

• Study Chair: Joel GUIGAY; GORTEC

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Groupe Oncologie Radiotherapie Tete et Cou
• ClinicalTrials.gov Identifier: NCT01289522
• Other Study ID Numbers: GORTEC 2008-03 TPEx; 2008-004869-25 ( EudraCT Number )
• First Posted: February 3, 2011
• Results First Posted: April 7, 2017
• Last Update Posted: May 15, 2017
• Last Verified: October 2016

Keywords provided by Groupe Oncologie Radiotherapie Tete et Cou:

Squamous cell carcinoma of the head and neck; recurrent or metastatic; first line chemotherapy; cetuximab; docetaxel; cisplatin; antineoplastic agents; First Line Palliative Treatment

Additional relevant MeSH terms:

Carcinoma; Neoplasm Metastasis; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Cetuximab; Antineoplastic Agents, Immunological; Antineoplastic Agents