E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable or Inoperable locally advanced head and neck squamous cell carcinoma without any prior chemotherapy or radiotherapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041823 |
E.1.2 | Term | Squamous cell carcinoma |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Main objective of the translational research is to try to identify molecular markers of resistance to the combination of an mTOR inhibitor with carboplatin and paclitaxel. If a sub-group of patients clearly better responding to this combination is identified, it could be the rationale to conduct a phase III trial stratified on these molecular markers. All biopsy samples will be performed; first non tumoral tissue and mucosal of head then tumor in duplicate and frozen immediately and first sent to the Department of Anatomy Pathology of the Hospital where biopsies was performed. Samples will thereafter be sent to the Centre de Ressources Biologiques of Beaujon Hospital for molecular analysis. All blood samples collected at baseline (W0), W1, W4 and W9 will be sent to the Department of Biochemistry of Beaujon Hospital |
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E.3 | Principal 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 |
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |