recurrent or metastatic head and neck squamous cell carcinoma MedDRA version: 17.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: DOCETAXEL
Product Code: DOCETAXEL
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: DOCETAXEL
Other descriptive name: DOCETAXEL
Product Name: FLUOROURACILE
Product Code: L
Sponsors
GORTEC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients: ? 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 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 12 weeks. ? 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 416 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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. ? 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 any study medication ? 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 ? 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 inform consent. ? Pregnant or breast feeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to compare in terms of overall survival the TPEx and EXTREME regimens as first line treatment of patients with recurrent / metastatic HN SCC;Secondary Objective: To compare TPEX regimen and EXTREME regimen in terms of : - Objective response rate (complete response (CR) or partial response (PR) according to RECIST 1.1 criteria) at 12 weeks (centralized review) - Best overall objective response rate (PR or CR or SD with confirmation of CR or PR by a second assessment 6 weeks later) - Progression free survival (PFS) - Time to progression (TTP) - Toxicity (all grades, according to CTC-NCI V4) - Compliance with chemotherapy and Erbitux - Health related quality of life (QL) assessed by EORTC QLQ-C30 questionnaires Ancillary objectives : - A multinational cost-effectiveness study will be performed alongside the trial to determine the most efficient regimen. - Study of the impact of p16 / HPV tumor status on the efficacy difference of the 2 regimens in patients with oropharyngeal initial tumor;Primary end point(s): Overall survival (OS): defined as the time to death from any cause measured from randomization. Patients with disease progression may be treated with off protocol therapy but will be followed for overall survival evaluation;Timepoint(s) of evaluation of this end point: Overall Survival will be evaluated one year after the end of the treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Objective response rate (complete response (CR) or partial response (PR) according to RECIST 1.1 criteria and assessed by central imaging review) at 12 weeks. For the statistical analysis of this endpoint, patients not evaluable (whatever the reason, including death) will be considered as failure (i.e. no CR, no PR) for this endpoint. ? Best overall tumor response rate (RECIST 1.1 criteria) during chemotherapy and maintenance: CR or PR or SD confirmed for CR or PR by a second assessment 6 weeks later ? Progression free survival (PFS): minimum time from randomization to progression as defined by RECIST 1.1 criteria or to death from any cause. Patients who don't have any of these events are censored at the date of last follow-up. ? Time to Progression (TTP): minimum time from randomization to progression as defined by RECIST 1.1 criteria. In case of death from other cause than cancer and no prior progression, the patient will be censored at the time of death. In case of death related to cancer without an accurate date of progression before death, the patient will be considered in progression at the time of death. In the event of no progression and no death, the patient will be censored at the date of last follow-up. ? Toxicity (according to CTC-NCI V4): all grades ? Compliance: Insufficient compliance for cetuximab is defined as a patient missing more than 2 consecutive infusions of cetuximab, even if the missed infusions are due to toxicity. Insufficient compliance for chemotherapy is defined as a patient missing more than 2 consecutive infusions of chemotherapy, even if the missed infusions are due to toxicity. ? Health related quality of life (QoL) assessed by EORTC QLQ-C30. The primary endpoint of the QoL study is the global health status/quality oflife scale of the QLQ-C30 questionnaire. ? Quality-adjusted life-years (QALYs) based on Euroqol EQ-5D measurements ? Net monetary benefit;Timepoint(s) of evaluation of this end point: Disease e | — |
Countries
France, Germany, Spain
Contacts
Public ContactDr. Juan Carlos Adansa
Hospital Universitario de Salamanca
Outcome results
None listed