E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10018336 |
E.1.2 | Term | Glioblastoma |
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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 |
The general objectives are to assess the safety of add-on dasatinib to Standard of Care (CCNU) as well as to assess the activity of this add-on therapy in GBM patients who have relapsed after Standard with temozolomide and radiotherapy. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
*Patients with histological or cytological proven glioblastoma multiforme, including anaplastic oligoastrocytoma with necrosis. * Recurrent or progressive disease documented by MRI after prior therapy (standard radiotherapy with concomitant and adjuvant temozolomide), within at least two weeks prior to registration/randomization on study. No other chemotherapy regimens apart from temozolomide are allowed. Prior exposure in the adjuvant setting to biotherapies/targeted agent is allowed if at least 4 weeks have elapsed since end of treatment and patients have recovered from all toxicity. * Patient may have been operated for recurrence. If operated, residual and measurable disease after surgery is not required but surgery must have confirmed the recurrence. In case of operation, a postsurgery MRI must be available within 48 hours following surgery. Surgery should be completed for at least 2 weeks before registration and patients should have fully recovered. * For non operated patients, recurrent disease must be at least one bidimensionally measurable target lesion (contrast enhancing lesion) with one diameter of at least 2 cm, based on MRI scan done within two weeks prior to registration/randomization. * For the safety phase only: Patients respiratory function evaluated by carbon monoxide diffusion capacity (DLCO) must be more than 60 % of the predicted value. * Age ≥ 18 years. * WHO Performance status 0 - 2 * Patients must be on a stable or decreasing dose of corticosteroids for at least 1 week prior to treatment start, regardless of their surgical status. * Completion of prior radiotherapy to the brain more than 3 months prior to the diagnosis of progression. * Patients who require anti-convulsant therapy must be taking non-enzyme inducing antiepileptic drugs (non-EIAED). Patients previously on EIAED must have been switched to non-EIAED at least two weeks prior to study entry. * Normal hematological functions: neutrophils ≥ 1.5 x 10E9 cells/l, platelets ≥100 x 10E9 cells/l * Normal liver function: bilirubin < 1.5 x upper limit of the normal range (ULN), alkaline phosphatase and transaminases (ASAT) < 2.5 x ULN. * Serum creatinine < 1.5 x ULN. * Clinically normal cardiac function without history of ischemic heart disease in the past 12 months. * All patients (male and female) must use effective contraception methods according to CPMP/ICH/286/95 if of reproductive potential (e.g. implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomised partner). * Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject. * WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as: - Amenorrhea ≥ 12 consecutive months without another cause or for women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL - Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. - WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product. |
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E.4 | Principal exclusion criteria |
* Prior chemotherapy for recurrent disease. * Prior Gliadel wafers. * Prior treatment with high dose radiotherapy (> 65 Gy), stereotactic radiosurgery or internal radiation therapy unless the recurrence is subsequently histologically confirmed. * History of pulmonary disease that may affect pulmonary functions including obstructive chronic broncho-pneumopathy, concurrent pleural effusion and interstitial pneumonia. * Presence of cardiac insufficiency NYHA grade III and IV, unstable angina, arrhythmia. Patients with stable ischemic heart disease for at least 12 months (e.g. treated prior angina, stable under appropriate therapy) are eligible. * Previous or current malignancy at other sites within the last 3 years with the exception of cone biopsied carcinoma of the cervix and adequately treated basal or squamous cell skin carcinoma
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety phase: The primary end-point will be the safety and tolerance of dasatinib-CCNU combination in order to establish a recommended dose for the phase II part. Phase II part: The principal end-point will be PFS probability at 6 months /Patients alive and free of progression at 6 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 | 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 |
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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 | 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) | 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 | 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) | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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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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 | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |