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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this single arm phase II study is to evaluate an alternating weekly regimen of temozolomide if and monthly fotemustine combination can significantly increase the progression free survival in the treatment of pre-treated, recurrent GBM patients. |
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E.2.2 | Secondary objectives of the trial |
Safety, Median Survival Time, RX responses |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1.Signed and dated IRB-approved Informed Consent. 2.Histologically proven (at diagnosis) Glioblastoma Multiforme (GBM) 3.Recurrence or progression after treatment with surgery, radiotherapy and chemotherapy, including temozolomide 4.Age more between 18 years 5.KPS 18 and 70 years enclosed 6.Life expectancy of at least 12 weeks 7.Negative pregnancy test (if female in reproductive age) 8.Agreement upon the use of effective contraceptive methods (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation, if men and women of child-producing potential 9.Acceptable liver function: - Bilirubin  1.5 upper limit of normal (ULN) - Albumin  3.0 g/dL - AST (SGOT), ALT (SGPT)  2.5 ULN (if liver metastases are present, then  5 ULN is allowed) - Alkaline phosphatase  2.5 ULN (if liver and/or bone metastases are present, then  5 ULN is allowed) 10.Acceptable renal function: Serum creatinine ≤1.5 mg/dl (or ≤133 µmol/L) 11.Acceptable hematologic status: - ANC  1,500 cells/mm3 - Platelet count  100,000 cells/mm3 - Hemoglobin  10.0 g/dL 12.At the time of first dose of study combination, at least 4 weeks must have elapsed since completion of prior temozolomide therapy, prior radiotherapy, prior surgery (at least 6 weeks since completion of prior nitrosurea therapy) 13.With the exception of alopecia, resolution of all acute toxic effects of any prior surgery, radiotherapy, radiosurgery or chemotherapy to NCI CTC (Version 3.0) Grade < 1 and to the baseline laboratory values as defined in Inclusion Criteria Number 9, 10, 11. 14.All patients on treatment with anticonvulsants, should continue the anticonvulsant therapy with non-enzyme-inducing anticonvulsants (non-EIACs) 15.Concurrent steroids allowed, dose stable for at least 7 days before study entry 16.Able and willing to comply with scheduled visits, therapy plans, and laboratory tests required in this protocol 17.Presence of at least one  1.5 cm2 bi-dimensionally measurable lesion by gadolinium (Gd)-enhanced MRI scan, indicating progressive or recurrent disease, obtained at least 12 weeks after standard external-beam radiotherapy and within 14 days prior to treatment. 18.Patients in relapse, following 1st line chemotherapy including temozolomide. |
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E.4 | Principal exclusion criteria |
The presence of any of the following will exclude a subject from study enrollment: 1.Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1 2.Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy 3.Pregnant or breast feeding women 4.Known infection with HIV, active hepatitis B or hepatitis C 5.Prior high-dose chemotherapy with bone marrow or stem cell support 6.Previous (within the last 5 years) or current malignancies at other sites, except for adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri. 7.Current enrollment in another therapeutic clinical trial 8.Patients who have exhibited allergic reactions to temozolomide or fotemustine 9.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgement of the investigator, would make the patient inappropriate for entry into this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival at 6 months (PFS-6) |
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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 | 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 | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |