E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with non small cell lung cancer (NSCLC) have a high risk of developing brain metastasis, up to 40% as evaluated in autopsy studies. These patients are often heavily symptomatic and their life expectancy remains limited (median 5.4 months), using corticosteroids and radiotherapy or radiosurgery alone. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assess safety and toxicity of concomitant chemotherapy with TMZ at low dose during the whole brain radiation and later on at the 14 days on/14days off schedule in patients with cerebral metastases. |
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E.2.2 | Secondary objectives of the trial |
As additional parameters progression free survival at 6 month (PFS-6) and the duration of overall survival (OS) will be recorded and compared to patients receiving radiation therapy alone. Evaluation of Quality of Life analysis (EORTC QLQ-C 30 + Brain Cancer module) and evaluation of neurological functioning during treatment (optional) using the Mini Mental Score and the EFIT test (Edinburgh Functional Impairment Test), consisting of the nine hole peg test, the ten meter walk test, Boston Aphasia rating scale and the Williams Delayed Recall Test. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
·Prior histologic confirmation of NSCLC ·Optional: NSCLC histologic confirmation of metastasis of NSCLC ·Presence of bidimensionally measurable disease in the brain ·No previous or current malignancies at other sites with the exception of adequately treated in situ carcinoma of the cervix or basal and squamous carcinoma of the skin. ·Age: > 18 years ·No evidence of progression at extracranial sites ·Karnofsky Performance status ³ 60 % ·ANC > 1.500/mm3 , platelets > 100.000/mm3, hemoglobin > 8g/dl ·Serum creatinine and bilirubine < 1.5 times upper normal limit of testing laboratory ·SGOT; SGPT < 3 times upper limit of testing laboratory ·Palliative radiation therapy to thorax and bone or other organs (except brain) is acceptable. ·Prior neurosurgery > 2 weeks from initiating treatment with TMZ ·Cortisone medication stable or decreasing within 2 weeks prior to initiating treatment with TMZ ·Patient is not pregnant or nursing and is advised and willing to use an effective method of contraception ·Written informed consent
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E.4 | Principal exclusion criteria |
·Chemotherapy or biologic therapy within four weeks prior initiating therapy with TMZ ·Prior radiation therapy for brain < 4 weeks from initiating therapy with TMZ ·Surgery within two weeks prior to TMZ administration ·Known HIV disease ·Acute infection requiring intravenous antibiotics ·Rapid disease progression outside of brain at study entrance. ·Any reason making compliance to the protocol improbable
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E.5 End points |
E.5.1 | Primary end point(s) |
The objective of this trial is to assess safety and toxicity of concomitant chemotherapy with Temozolomide (TMZ) at low dose during the whole brain radiation and later on at the two weeks on, two weeks off schedule in patients with cerebral metastases from non small cell lung cancer (NSCLC). |
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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 | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | 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 | 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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
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 | 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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The active phase of the trial ends after the evaluation of activity, safety and QoL following the 6th cycle of sequential Temodal given to the last patient. Survival data will be collected for 12 additional months |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |