E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
brain metastastases of non-small or small cell lung cancer |
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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 |
Main objective : To compare, in terms of time to progression (TTP) of the brain metastases, maintenance therapy with enzastaurin plus BSC vs. placebo plus BSC in patients with brain metastases from lung cancer who have completed whole brain radiotherapy |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives :• To compare time to objective progression of brain metastases, overall progression free survival and overall survival between treatment arms. To compare response rates on extra-cranial tumor manifestations. To compare adverse events between treatment arms. To compare health-related quality of life using the EORTC QLQ-C30 questionnaire with its brain module BCM 20. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients are eligible to be included in the study only if they meet all of the following criteria: [1] Histologically or cytologically proven SCLC or NSCLC [2] Brain metastases radiologically proven prior to start of WBRT. If solitary brain metastasis: Surgery or radiosurgery should be considered first. If not eligible for surgery or radiosurgery, the patient may be included in the study. [3] Having received WBRT with either 3 Gy x 10, 4 Gy x 5 or 5 Gy x 4. Sites will decide which WBRT schedule will be used. Preferably, one fractionation scheme should be used for all patients enrolled at each site. [4] No other previous radiotherapy to the brain will be allowed except for radiosurgery at one occasion [5] Patients must be able to start enzastaurin within 14 days after the last fraction of WBRT. [6] ECOG performance status 0 to 2. (See protocol attachment S020.6) [7] Patients must have adequate organ function, including the following: • Adequate bone marrow reserve: white blood cell (WBC) count 3.0 109/L, absolute neutrophil count (ANC) 1.5 109/L, platelet count 75 109/L and hemoglobin 9 g/dL. • Hepatic: bilirubin 2 times the upper limit of normal (ULN); alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) 3 ULN, or 5 ULN with liver metastases • Renal: serum creatinine 1.5 ULN. [8] Age 18 years or older [9] For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen (for example, intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after the treatment period; Women with reproductive potential must have a negative serum or urine pregnancy test within 7 days before study enrollment and must not be breast-feeding. For men: Must be surgically sterile, or compliant with a contraceptive method during and for 3 months after the treatment period. [10] Written informed consent
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria: [11] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. [12] Have previously completed or withdrawn from this study or any other study investigating enzastaurin [13] Are unable to swallow tablets or show conditions which could interfere with oral medication intake (e.g. vomiting, partial bowel obstruction. [14] Are unable to discontinue use of carbamazepine, phenobarbital or phenytoin (refer to Section 5.7) prior to inclusion. The investigator may prescribe non-EIAEDs. However if the patient requires therapy with these drugs after starting enzastaurin treatment, the patient may remain on study therapy [15] Having concurrent administration of warfarin [16] Showing hemophilia [17] Having had any systemic anti-cancer treatment within the last 2 weeks prior to enrolment. [18] Showing conditions – medical, social, psychological – which could prevent adequate information and follow-up [19] Showing serious concomitant systemic disorders (for example, active infection or abnormal electrocardiogram (ECG) that in the opinion of the investigator, would compromise the safety of the patient or his/her ability to complete the study [20] Having clinically active cancer other than the NSCLC / SCLC
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary study aim is to compare the time to progression TTP of the brain metastasis, defined as the time from the date of study enrollment (randomization) to the date of first observation of progression of the brain metastases. Progression of the brain metastases will be evaluated according to RECIST criteria using MRI technology. Analysis of TTP of the brain metastasis will be done including both objective and clinical progression. Assessments of tumor brain metastases will be performed using radiological techniques (MRI) until observation of objective progression. However, if the PS or neurological status of a patient worsens to such an extent that radiological confirmation of progression is not feasible, investigator may discontinue the patient based on the clinical progression of the brain metastasis. In these cases, the date of increased steroids dose will be considered the date of progression for the purpose of TTP analysis.
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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 | No |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Patient reported outcomes- Quality of Life |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |