Phase I/II study of Induction Chemotherapy with weekly RAD001, Carboplatine and Paclitaxel in Unresectable or Inoperable Locally Advanced Head and NeckSquamous Cell Carcinoma (HNSCC) - CAPRA
- Conditions
- nresectable or Inoperable locally advanced head and neck squamous cellcarcinoma without any prior chemotherapy or radiotherapyMedDRA version: 9.1Level: PTClassification code 10041823Term: Squamous cell carcinoma
- Registration Number
- EUCTR2008-005702-39-FR
- Lead Sponsor
- GERCOR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 50
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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Phase I: <br>To determine the safety profile of weekly RAD001 in combination with carboplatin and paclitaxel in chemonaive patients with unresectable or inoperable locally advanced HNSCC.<br><br>Phase II: To assess anti-tumor activity of the combination in these patients.;Secondary Objective: Secondary objectives<br>· To identify molecular markers of resistance to this combination.<br>· To describe the pharmacokinetics of RAD001, carboplatin and paclitaxel.<br>· To assess objective response rate after completion of radiation therapy (only<br>for patients in the phase II part);Primary end point(s): Primary endpoints:<br>Phase I: <br>To determine the maximum tolerated dose (MTD) and recommended dose<br>(RD) of weekly RAD001 in combination with carboplatin and paclitaxel in<br>chemonaive patients with unresectable or inoperable locally advanced HNSCC<br>(phase I part).<br>Phase II: <br>To assess the objective response rate of the combination according to the<br>RECIST criteria
- Secondary Outcome Measures
Name Time Method