recurrent or progressed WHO grade IV intracranial glioblastoma
Conditions
Interventions
Trade Name: Velcade
Product Name: Velcade
Product Code: bortezomib
Pharmaceutical Form: Powder for concentrate for solution for injection/infusion
Trade Name: Temodal
Product Name: Temozolomide
Pharm
Sponsors
Helse Bergen HF
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All of the following conditions must apply to the prospective patient at screening prior to receiving study agent (e.g.): ? Histologically confirmed recurrent or progressed WHO grade IV intracranial glioblastoma (GBM), MRI evidence of recurrence within 14 days prior to enrolment ? Unmethylated MGMT promoter characterised from tissue obtained at operation ? Must submit an unstained paraffin block and cryopreserved tumour tissue from surgical procedure ? Must be >- 18 years old, with a life expectancy > 8 weeks ? Cranial MRI or contrast CT scan showing tumour relapse = 12 weeks since radiation treatment ? Measurable recurrent tumour ? Tumour not available for radiosurgery ? Written informed consent for study participation and tumour, blood sample collection obtained before performance of any study related procedure, and not part of normal medical care. ? Karnofsky performance status = 70% ? WBC = 3,000/mm^3 ? ANC = 1,500/mm^3 ? Platelet count = 100,000/mm^3 ? Prothrombin time/international normalized ratio (PT INR) =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: - hypersensitivity to Bortezomib, boron, or mannitol - Peripheral neuropathy = grade 2 - Myocardial infarction within the past 6 months - NYHA class III or IV heart failure - Uncontrolled angina - Severe uncontrolled ventricular arrhythmias - LVEF = 45 % at echocardiography - Electrocardiographic evidence of acute ischemia or active conduction system abnormalities - serious medical or psychiatric illness that would interfere with study participation including, but not limited to, any of the following: - Ongoing or active infection requiring IV antibiotics - Psychiatric illness and/or social situations that would limit compliance with study requirements - Ongoing, uncontrolled infection requiring IV antibiotics - Disorders associated with a significant immunocompromised state (e.g., HIV, systemic lupus erythematosus) - history of stroke within the past 6 months - other malignancy within the past 3 years except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy (i.e., cervical cancer), or low-risk prostate cancer after curative therapy - significant medical illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy - disease that will obscure toxicity or dangerously alter drug metabolism - viral hepatitis (HBV surface antigen positive) or active hepatitis C infection - concurrent investigational drugs (chemotherapy) must be stopped at least 4 weeks prior to therapy. - concurrent inducers of CYP450 3A4 (e.g., enzyme-inducing anti-epileptic drugs [EIAED] e.g. phenytoin, fosphenytoin, carbamazepine, phenobarbital, or primidone) - Another ongoing experimental therapy - Any contraindications for use of Temozolomid
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase IB: Assessment of safety and tolerability of Bortezomib administered with Temozolomide. Determination of the optimal dose of TMZ and BTZ given as combination therapy Phase II: Assessment of efficacy of Bortezomib administered with Temozolomide. Estimation of the median progression free survival (PFS) and overall survival (OS) of patients with recurrent or progressed glioblastoma after pre-treatment with Bortezomib prior to combination with Temozolomide as well as progression free rate at 6 months ;Secondary Objective: Key secondary objectives •Determine physiological, molecular and biochemical changes in blood and tumour tissue that correlate with treatment responses: - Changes in natural killer cell phenotype and function - Changes in autophagy flux -Abrogation of 26S proteasome activity ;Primary end point(s): •Assessment of efficacy of Temozolomide administered together with Bortezomib in recurrent glioblastoma. Overall survival (OS) at 1 year [from operation date histologically diagnosing GBM to date of death] •Assessment of safety and tolerability of Bortezomib administered with Temozolomide ;Timepoint(s) of evaluation of this end point: 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Toxicity assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Progression free survival at 6 months [from date of enrolment to date of progression or death] - Time to progression (TTP) - [ from date of enrolment to date of date of progression] - Tumour response as assessed by contrast enhanced MRI using RANO criteria and neurological exam - [Time Frame: MRI at start of treatment and every 8th week, neurologic exam every 4 weeks] After completion of treatment, follow up MRI will be performed at 8th week, then every 8th week until endpoint evaluation at 6 months. If objective responses are observed, then MRI every 12 weeks until the 1-year endpoint. Correspondingly, Neurologic exam and KPS at same time points. Patients responding to the therapy without treatment related toxicity rendering its discontinuation will receive therapy until progression and/or consent withdrawal. ;Timepoint(s) of evaluation of this end point: See above | — |
Countries
Norway
Contacts
Public ContactDorota Goplen
Helse Bergen HF
Outcome results
None listed