E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Brain metastases from primary non-small cell lung cancer (NSCLC). |
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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 |
The primary objective of this study is to evaluate the efficacy of treatment with either oral topotecan plus WBRT or WBRT alone in patients with brain metastases due to NSCLC. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to assess the safety and tolerability of treatment with either oral topotecan plus WBRT or WBRT alone.
The pharmacogenetic and proteomic research objectives are as follows: • Investigate the relationship between genetic variations in select candidate genes in the host DNA and response (safety, efficacy, and tolerability) following treatment with topotecan. • Evaluate the baseline protein profile in a plasma sample taken at baseline and correlate with response to topotecan therapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed written informed consent - Patients must be ≥18 years of age - Performance status ECOG 0, 1, or 2 - Patients with radiologically confirmed (symptomatic or asymptomatic) brain metastases from histologically confirmed primary NSCLC - Presence of at least one brain lesion that is bidimensionally measurable by CT or MRI. - Patients must have received at least one prior chemotherapy regimen for the treatment of primary disease (NSCLC). Single-agent treatment with a tyrosine kinase inhibitor will not be considered prior chemotherapy. - Prior brain surgery is acceptable provided at least one brain lesion that is bidimensionally measurable by CT or MRI is present. - At least 4 weeks must have elapsed since any surgery. - At least 4 weeks must have elapsed since any radiation therapy to a non-CNS site. - Patients must have adequate bone marrow, renal, and liver capacities - Women of child-bearing potential with adequate contraception (e.g. oral contraceptives, diaphragm plus spermicide, or IUD) for at least 3 months prior to study start. The same contraceptive method should be used throughout the study and continued for at least 4 weeks after the end of the study. |
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E.4 | Principal exclusion criteria |
- Prior radiation therapy to the CNS. - Patients who have received prior treatment with topotecan. - Patients who have received any investigational agent (for any tumor) within 30 days or 5 half-lives (whichever is longer) prior to randomization. - Concomitant therapy with known inhibitors of BCRP or P-glycoprotein, such as erlotinib or gefitinib. - Any severe concurrent medical condition, including an active infection, that could affect the patient's ability to comply with the protocol. - Any known primary or secondary immunodeficiencies. - Any condition of the GI tract which would affect GI absorption or motility (e.g., autonomic neuropathy, active gastric or duodenal ulcers or certain gastrointestinal surgeries). Patients receiving medication to maintain motility or gastric emptying are also excluded. - Patients with uncontrolled emesis, regardless of etiology. - Women who are pregnant or lactating. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is overall survival. The secondary endpoints are: 6-month survival rate, response rate (CNS-radiologic), time to response (CNS-radiologic), time to progression (CNS-radiologic), time to progression (all sites-radiologic) and assessment of neurological signs and symptoms. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | Yes |
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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Please refer to the protocol for more details (section 3.1.). |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
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 | 1 |