Platinum-Cetuximab Combined With Docetaxel or With 5FU in Patients With Recurrent/Metastatic HNSCC
Conditions
Head and Neck Squamous Cell Carcinoma
Conditions: official terms
Carcinoma, Squamous Cell - Head and Neck Neoplasms
Conditions: Keywords
Recurrent/Metastatic HNSCC, Taxanes
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Cisplatin Type: Drug
Name: 5-Fluorouracile Type: Drug
Name: Docetaxel Type: Drug
Name: Cetuximab Type: Drug
Name: granulocyte colony-stimulating factor (G-CSF) Type: Drug
Overall Status
Recruiting
Summary
This study evaluates the efficacy of the new docetaxel-cisplatin-cetuximab regimen (TPEx) versus the standard platinum-5FU-cetuximab EXTREME regimen as a first-line treatment in recurrent and/or metastatic HNSCC. Half of patients will be treated by TPEx regimen, while the other half will be treated by EXTREME regimen.
Detailed Description
The EXTREME regimen, i.e. cetuximab added to platinum (100 mg/m² every 3 weeks ) and 5FU (96h continuous infusion at 1000 mg/m²/day every 3 weeks) during 6 cycles of treatment and continued as maintenance in patients with stable disease, is currently the standard of care in first line recurrent metastatic HNSCC.

From our previous experience (phase II GORTEC "TPEx" study), the TPEx regimen of 4 cycles of docetaxel-cisplatin-cetuximab followed by maintenance with cetuximab every 2 weeks seems more efficient (overall survival) compared to EXTREME regiment. Docetaxel combined with cisplatine (each administered at 75mg/m² every 3 weeks) also appeared more convenient than the standard Cisplatin-5FU-Cetuximab EXTREME regimen (4 cycles of chemotherapy instead of 6 cycles and no i.v. continuous infusion). Toxicity was manageable with G-CSF support. In addition the toxicity / efficacy profile also seems favourable as suggested by the excellent dose intensity achieved and the high rate of patients (78%) who were able to start maintenance therapy.

Taking together all these considerations, the TPEx regimen might be a good substitute for EXTREME as first-line treatment in patients with recurrent metastatic HNSCC, and it is justified and necessary to perform a direct comparison in a randomized trial to further test this hypothesis.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 71 Years
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Histologically confirmed diagnosis squamous cell carcinoma of head and neck: oral cavity, oropharynx, hypopharynx, larynx (histological confirmation is mandatory at least for initial diagnosis)

- Recurrence and/or metastatic disease not suitable for local therapy

- At least one measurable lesion (RECIST) by CT or MRI

- PS < 2

- Age ≥ 18 years and < 71 years

- Clearance of creatinine > 60ml/mn (MDRD)

- Haematological function as follows: absolute neutrophil count > 1.5 x 109/l, platelet > 100 x 109/l, hemoglobin ≥ 9.5 g/dl

- Hepatic function as followed: bilirubin ≤ Upper limit of normal (ULN); SGOT/SGPT < 1.5 ULN; AP < 2.5 ULN

- Estimated life expectancy > 12 weeks

- Informed Consent Form signed

- Affiliation to an health insurance

- Negative pregnancy test in women of childbearing potential within 14 days prior to treatment initiation (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization). Both men and women (of childbearing potential) who are sexually active must use adequate contraception, during and for at least 6 months post-treatment.

Exclusion Criteria:

- Patients with nasopharyngeal cancer, paranasal sinus cancer or unknown primary

- Prior systemic chemotherapy for the head and neck carcinoma, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to study entry

- Surgery (excluding diagnostic biopsy) or radiotherapy within 6 weeks before study entry

- Contra-indication to receive cisplatin

- Known dihydropyrimidine dehydrogenase (DPD) deficiency

- Administration of prophylactic phenytoin

- Recent or planed yellow fever vaccination

- Prior dose of cisplatin > 300 mg/m² (a patient who received prior RT + 3 cycles of cisplatin or 3 cycles induction TPF, i.e. total dose of cisplatin ≤ 300 mg/m², for locally advanced primary HN cancer can be included)

- Prior anti-EGFR treatment received less than 12 months before enrolment in the trial

- Known hypersensitivity reaction to 5FU, cisplatin, carboplatin, docetaxel or cetuximab

- Documented or symptomatic brain or leptomeningeal metastasis

- Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 12 months

- Malignancies within 5 years prior to randomization, with the exception of adequately treated basal or squamous cell skin cancer and carcinoma in situ of the cervix

- Active infection (infection requiring IV antibiotics), including active tuberculosis and known and declared human immunodeficiency virus (HIV).

- Significant disease which, in the judgment of the investigator, would make the patient inappropriate for entry into the trial.

- Any social, personal, medical and/or psychologic factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent.

- Pregnant or breast feeding women
Locations
Institut Sainte Catherine
Avignon, France
Status: Not yet recruiting
Contact: Armelle Rollet, CRA - 04 90 27 62 74 - a.rollet@isc84.org
Centre Hospitalier de la Dracénie
Draguignan, France
Status: Recruiting
Centre Médical de Forcilles
Ferolles Attily, France
Status: Not yet recruiting
Clinique des Ormeaux
Le Havre, France
Status: Recruiting
Contact: Angelique PICARD, CRA - 02 32 79 21 81 - a.leclerc.onco-normand@orange.fr
Centre Hospitalier de Bretagne Sud (CHBS)
Lorient, France
Status: Recruiting
Centre Léon Bérard
Lyon, France
Status: Not yet recruiting
Hôpital de la Timone
Marseille, France
Status: Not yet recruiting
ICM Val d'Aurelle, Montpellier
Montpellier, France
Status: Not yet recruiting
Centre Antoine-Lacassagne
Nice, France
Status: Recruiting
Val de Grace
Paris, France
Status: Recruiting
Centre Eugene Marquis
Rennes, France
Status: Not yet recruiting
Centre Henri Becquerel
Rouen, France
Status: Not yet recruiting
Institut de Cancérologie de l'Ouest (ICO) René Gauducheau
Saint Herblain, France
Status: Not yet recruiting
L'Institut de Cancérologie de Lorraine (ICL) Alexis Vautrin
Vandoeuvre les Nancy, France
Status: Recruiting
Gustave Roussy
Villejuif, France
Status: Not yet recruiting
Charité Campus Benjamin Franklin
Berlin, Germany
Status: Not yet recruiting
Instituto Catalá de Oncologia (ICO)
Barcelona, Spain
Status: Not yet recruiting
Start Date
October 2014
Completion Date
December 2017
Sponsors
Groupe Oncologie Radiotherapie Tete et Cou
Source
Groupe Oncologie Radiotherapie Tete et Cou
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page