E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic squamous cell carcinoma of the head and neck |
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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 | LLT |
E.1.2 | Classification code | 10063569 |
E.1.2 | Term | Metastatic squamous cell carcinoma |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
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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: 1. To determine the safety and tolerability of the combination of RAD001 (everolimus) and docetaxel 2. To determine the maximum tolerated dose of RAD001 (everolimus) when combined with docetaxel
Phase II: 1. To examine the response rates in patients receiving the combination of docetaxel and RAD001 (everolimus) and those receiving docetaxel alone. |
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E.2.2 | Secondary objectives of the trial |
Phase I: 1. To investigate possible pharmacokinetic interactions between docetaxel and RAD001 (everolimus) 2. To investigate the effect of RAD001 on downstream targets of mTOR in tumour
Phase II: 1. To examine the time to progression after docetaxel and RAD001 (everolimus)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Histologically confirmed advanced/recurrent or metastatic squamous cell carcinoma of the head and neck -Life expectancy >= 12 weeks -ECOG 0 or 1 -Measurable disease (RECIST criteria) -Age >= 18 years -Written informed consent and able to attend for treatment and follow-up -Adequate haematological, renal and liver function -Patients may have received one line prior chemotherapy (not taxanes) -Patients may have received prior radiotherapy (completed >= 6 months prior to recruitment) -Negative pregnancy test (women of CBP) and willing to use approved contraception method (all patients) |
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E.4 | Principal exclusion criteria |
-Potentially curable disease -Disease relapsed within 6 months of radiotherapy -Patients with locally advanced disease for whom radiotherapy is indicated -Previous chemotherapy for any cancer, except for head and neck cancer -Previous therapy with any erbB inhibitors (except Cetuximab given radiotherapy, as indicated in treatment algorithm) -Treatment within the last 4 weeks with any investigational drug -The current use of drugs which are known to inhibit CYP3A4 (except dexamethasone), or block P-glycoprotein including grapefruit juice -Evidence of the presence of central nervous system metastases -Evidence of uncontrolled infection -Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study -History of hypersensitivity to docetaxel or any of its excipients -Pregnant or breast-feeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I: -Safety/tolerability and MTD determination -Pharmacokinetic interactions of combined RAD001 and docetaxel -To investigate effects of RAD001 on downstream targets of mTOR in tumour
Phase II: -Response -Time to progression and identification of predictors of response |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Phase I is a dose escalation study; Phase II study will be randomised |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 6 |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |