E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary malignant brain tumors |
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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 |
Determine the disease control rate (progression free survival (PFS), response rate (RR) of the combination bevacizumab and irinotecan (BI) in patients with recurrent primary brain tumors. |
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E.2.2 | Secondary objectives of the trial |
Determine safety, tolerability and toxicity in patients with recurrent or progressive primary brain tumors Determine overall survival (OS). Correlate tumor response with the expression of plasma tumor markers and PET results of metabolism and blood flow.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
·Written informed consent ·Histological verification of primary malignant brain tumor, or grade II glioma, meningeoma or ependymoma with progression and no other treatment options (including brain stem gliomas without histological verification) ·Recurrence or progression after standard treatment (debulking surgery of possible, radiotherapy and temozolamide or other chemotherapy within last six months) ·Evidence of measurable recurrent progressive disease (CT/MRI scan) ·An interval of at least 4 weeks between prior surgical resection and study enrolment ·An interval of at least 4 weeks between prior radiotherapy or chemotherapy and enrolment on this protocol. ·PS 0-2 (ECOG scale) ·Age > 18 ·Life expectancy > 3 month ·Normal organ function: - Platelets > 125 x 109/l - Hemoglobin >6,2 mmol/l - Leukocytes > 3 x 109/l - ACN> 1,5 x 109/l - ASAT or ALAT < 3 x upper normal limit - Bilirubin < 1,5 x upper normal limit - Creatinine clearance > 45 ml/min - APTT < normal limit - INR < normal limit ·Fertile females must use oral contraceptive, IUD (intrauterine device) or preservatives. Fertile males must use preservatives.
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E.4 | Principal exclusion criteria |
·Radiotherapy or chemotherapy within the last 4 weeks. ·Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids ·Any condition (medical, social, psychological), which would prevent adequate information and follow-up ·Any other active malignancy or previous malignancies within the last 5 years, except, adequately treated basal or squamous cell carcinoma of the skin, or carcinoma in situ. ·Any significant cardiac disease (New York Heart Association Class II or greater), arytmia, congestive heart failure, acute myocardial infarction within 6 months or unstable angina pectoris. ·Clinically significant peripheral vascular disease ·Evidence of bleeding diathesis, coagulapathy or taking ASA, NSAIDs or clopidogrel ·Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the curse of the study ·Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0 ·History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 month prior to day 0 ·History of known HIV, Hepatitis B and Hepatitis C negative ·Any ongoing infection, uncontrolled diabetes mellitus, serious non-healing wound, ulcer or bone fracture ·Pregnancy or breast feeding ·Requires therapeutic anti-coagulation ·Blood pressure > 150/100 mmHG ·Grade 2 or greater proteinuria
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E.5 End points |
E.5.1 | Primary end point(s) |
This is an investigator-initiated, open label phase II study, where patient with recurrent primary brain tumors will be considered for the study.
The patient population will include a total of evaluable 54 patients. The expected rate of accrual is 3-6 patients a month. The estimated study start date is October 2006, with the last patient enrolled in April 2008. With additional follow up, the clinical part of the study will be completed in April 2010.
The patients will be followed according to the Schedule of Study Events (Appendix 3).
All patients will be followed until disease progression or death is documented or a follow-up of 2 years is reached. During this follow-up period tumor response measurements will be carried at Rigshospitalet. If the patient goes off study for any reason other than PD, they still will be evaluated every 3 months for survival.
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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 | Yes |
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 | No |
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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
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 | 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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |