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. Two-thirds of NSCLC patients have advanced disease and are considered incurable by surgery or chest radiation. The current standard of care for these patients is chemotherapy. Novel therapeutic agents are under development. Epidermal growth factor inhibitors have already demonstrated a clinical benefit to patients with advanced NSCLC failing standard chemotherapy regimens. |
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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 | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
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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 |
Overall, this study aims to assess the value of combined treatment with RAD001 and erlotinib in patients with advanced NSCLC previously treated only with hemotherapy as systemic therapy. The study consists of two consecutive phases, the primary aims of which are:
In phase 1 • To assess the feasibility (in terms of both dose and schedule) of combined daily or weekly administration of RAD001 with daily erlotinib based on evaluation of safety and PK drug-drug interaction and to establish the appropriate doses to carry forward into phase 2.
In phase 2 • To estimate the Disease Control Rate at 3 months (DCR at 3 months) as measure of anti-tumor activity in patients who receive RAD001 (daily and/or weekly schedule) together with daily erlotinib as compared to the DCR at 3 months in patients who receive erlotinib alone.
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E.2.2 | Secondary objectives of the trial |
In phase 1 • To assess the clinical efficacy of RAD001 and erlotinib combination schedule(s), based on evaluation of ORR (Objective Response Rate) and EPR (Early Progression Rate)
In phase 2 • To describe the clinical efficacy of all study treatments in terms of ORR, PFS (Progression Free Survival) and survival • To describe the safety profile of all study treatments • To assess steady state drug levels • To investigate potential molecular markers • To evaluate tumor metabolic response with FDG-PET imaging |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with advanced NSCLC (unresectable or metastatic) • Age ≥ 18 years old • Pathologic confirmation of NSCLC (must include accurate histology in phase 2 part of the study) • Patients entered on the phase 2 part of the study 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 • Previous chemotherapy treatment for advanced disease with documented tumor progression (serial CT scans demonstrating progressive disease according to RECIST must be available) despite ≤ 2 chemotherapy schedules for treatment of advanced disease (previous therapy for localized disease is not counted), one of which must have included cisplatin or carboplatin • More than two weeks since any major surgery, completion of radiation, or completion of all prior chemotherapy (adequately recovered from the acute toxicities of any prior therapy) • WHO performance status ≤ 2 in the phase 1 part of the study • WHO performance status ≤ 1 in the phase 2 part of the study • 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 ≤ grade 2 and 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 |
Patients will be excluded if they meet ANY of the following criteria: • Concurrent therapy with agents otherwise used in treatment of cancer (for example, methotrexate for rheumatoid arthritis) • Treatment with any other investigational drugs within the preceding 4 weeks • Prior treatment with an EGFR inhibitor (either a small molecule EGFR TK inhibitor or ant-EGFR antibody) • Chronic treatment with steroids or another immunosuppressive agent • Leptomeningeal or uncontrolled brain metastases, including patients who continue to require glucocorticoids or intrathecal chemotherapy for brain or leptomeningeal metastases (documented by lumbar puncture) • Malignancies other than lung cancer within the past 2 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 or previous seropositivity for the virus • Patients with active skin, mucosa, ocular or GI disorders of grade > 1 • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 or erlotinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) • 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 or erlotinib) • 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) |
Phase 1: assess feasibility (in terms of dose and regimen) based upon safety and pharmacokinetic drug-drug interaction Phase 2: disease Control Rate at 3 months (DCR at 3 months) |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Combined Phase I and II study |
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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 | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | 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 | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |