Unresectable or Inoperable locally advanced head and neck squamous cell carcinoma without any prior chemotherapy or radiotherapy MedDRA version: 9.1 Level: PT Classification code 10041823 Term: Squamous cell carcinoma
Conditions
Interventions
Product Name: Evérolimus
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Concentration unit: mg milligram(s)
Conc
Sponsors
GERCOR
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: inclusion criteria 1. Histologically proven squamous cell carcinoma of oral cavity, oropharynx, larynx or hypopharynx 2. Unresectable locally advanced disease (T4 N0-N3 of the TNM classification, or resectable with surgery contra-indication). 3. Presence of measurable lesions defined as those accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan 4. No prior therapy 5. Age = 18 years 6. WHO performance status = 2 7. Life expectancy more than 3 months 8. Adequate Hematology laboratory data within 7 days prior to registration Absolute granulocytes> 1.5 x 109/L Platelets > 100 x 109/L Hemoglobin = 9 g/dL 9. Adequate Biochemistry laboratory data within 7 days prior to registration Total bilirubin = 1.25 x upper the normal limit Transaminases = 2.5 xUNL Alkaline phosphatases = 5 x UNL Creatinine clearance = 60 mL/min Glycemia = 1.5 x UNL Cholesterolemia = 7.30 mmol/L 10. Adequate Hemostasis laboratory data within 7 days prior to registration TP within the normal range 11. Capacity to swallow pills 12. Women should be post-menopaused or willing to accept the use an effective contraceptive regimen during the treatment period and at least 3 months after the end of the study. All non menopaused women should have a negative pregnancy test within 72 hours prior to registration. Men should accept to use an effective contraception during treatment period and at least 3 months after the end of the study. 13. Absence of pre-existing grade = 2 neuropathy 14. O2 saturation > 88% 15. Signed written informed consent 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria 1. Stade I,II, III, IVc 2. Chemotherapy or radiotherapy prior to the study 3. Treatment with another investigational drug 4. Participation in another therapeutic trial within the 30 days prior to entering this study 5. Uncontrolled disease such as diabetes, hypertension, symptomatic congestive heart or pulmonary failure, renal or hepatic chronic diseases… (non exhaustive list) 6. Uncontrolled severe infectious disease, active hemorrhagic syndrome or anticoagulant therapy 7. Past history of cancer except in situ cervix cancer and baso-cellular skin carcinoma 8. Known brain metastases ; cerebral CT scan is not required if no symptomatology is present 9. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial 10. Concomitant medications: CYP3A4 strong inhibitors : azole antimycotics (itraconazole, ketoconazole) HIV protease inihibitor (ritonavir), erythromycin, anti-epileptic drugs (phenytoin, carbamazepine) (non exhaustive list ) 11. Pregnancy or lactation 12. Eligible for organ preservation program
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: To determine the safety profile of weekly RAD001 in combination with carboplatin and paclitaxel in chemonaive patients with unresectable or inoperable locally advanced HNSCC. Phase II: To assess anti-tumor activity of the combination in these patients.;Secondary Objective: Secondary objectives · To identify molecular markers of resistance to this combination. · To describe the pharmacokinetics of RAD001, carboplatin and paclitaxel. · To assess objective response rate after completion of radiation therapy (only for patients in the phase II part);Primary end point(s): Primary endpoints: Phase I: To determine the maximum tolerated dose (MTD) and recommended dose (RD) of weekly RAD001 in combination with carboplatin and paclitaxel in chemonaive patients with unresectable or inoperable locally advanced HNSCC (phase I part). Phase II: To assess the objective response rate of the combination according to the RECIST criteria | — |
Countries
France
Outcome results
None listed