E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lung cancer is one of the most common malignancies in developed countries and accounts for millions of deaths worldwide. In 2000, the annual incidence of non-small cell lung cancer (NSCLC), which comprises 80% of all lung cancer cases, was 991,089 and the worldwide mortality was 882,495. Unfortunately, two-thirds of NSCLC patients have advanced disease (clinical stage IIIB/IV) and are considered incurable by surgery or chest radiation. |
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MedDRA Classification |
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 |
To assess the clinical efficacy of RAD001, based on the evaluation of objective tumor response rate (RR) |
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E.2.2 | Secondary objectives of the trial |
• To assess the safety of RAD001 monotherapy • To assess additional clinical efficacy of RAD001, based on rate of early disease progression (EPR) • To assess the steady state levels of RAD001 in blood • To investigate potential molecular markers predictive of clinical effect
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Patients with advanced (unresectable or metastatic) NSCLC • Patients must have at least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. • Patients who have received ≤ 2 chemotherapy regimen, one of which must have included cisplatinum or carboplatin, and who have documented evidence of tumor progression (Arm 1)Patients who have received chemotherapy and small molecule EGFR inhibitor (as a separate regimen) with documented tumor progression despite at least 4 weeks therapy with either gefitinib or erlotinib (Arm 2) • Serial CT scans demonstrating progressive disease according to RECIST must be available • Pathologic confirmation of NSCLC with a tissue sample of the metastatic or primary tumor available for molecular marker analyses • Age ≥ 18 years • Minimum of two weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy). • WHO performance status £ 2 • Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hgb > 9 g/dL • Adequate liver function as shown by: serum bilirubin ≤ 1.5 x upper limit of normal (ULN), and serum transaminases activity ≤ 3 x ULN. With the exception of serum transaminases (< 5 x ULN) if the patient has liver metastases • Signed informed consent |
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E.4 | Principal exclusion criteria |
• Concurrent therapy with agents used other than as anticancer therapy (for example, methotrexate for rheumatoid arthritis) • Any investigational drug, other than EGFR inhibitor (Arm 2), within the preceding 4 weeks • Chronic treatment with steroids or another immunosuppressive agent • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases • Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin. • Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, unstable angina, or congestive heart failure - New York Heart Association Class III or IV, ventricular arrhythmias active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper GI tract ulceration) • A known history of HIV seropositivity • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) • Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin) • Women who are pregnant or breast feeding, or women able to conceive and unwilling to practice an effective method of birth control. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001) • History of noncompliance to medical regimens • Patients unwilling to or unable to comply with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
objective tumor response rate (RR) |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
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 | No |
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) | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |