BORTEZOMIB for Recurrent grade IV glioma | Glioblastoma | Grade IV IDH-mutated astrocytoma

Inclusion criteria

• {"criterion_text":"- Histologically confirmed recurrent or progressed WHO grade IV intracranial IDH wildtype glioblastoma (GBM) or grade IV IDH mutated astrocytoma, MRI evidence of recurrence within 14 days prior to enrolment\n- Written informed consent for study participation and tumour, blood sample collection obtained before performance of any study related procedure\n- Karnofsky performance status ≥ 70%\n- WBC ≥ 3,000/mm^3\n- ANC ≥ 1,500/mm^3\n- Platelet count ≥ 100,000/mm^3\n- Prothrombin time/international normalized ratio (PT INR) < 1.4.\n- Haemoglobin ≥ 10 g/dL (transfusion allowed)\n- Adequate hepatic function: serum bilirubin, AST, ALT and alkaline phosphatase ≤ 2.5 upper limit of normal (ULN)\n- Serum potassium within normal limit\n- Serum sodium > 130 mmol/L\n- Unmethylated MGMT promoter characterised from tissue obtained at operation\n- Estimated GFR ≥ 60\n- Stable or reduced doses of corticosteroids for at least 1 week prior to enrolment, but analgesics and other drugs to treat symptoms or prevent complications allowed\n- Patients receiving EIAED must be transitioned to non-EIAED at least 2 weeks before study inclusion\n- Unfractionated and/or low molecular weight heparin is allowed\n- Other investigational drugs must be discontinued at least 12 weeks prior to study entry unless treatment failure under other experimental therapy is confirmed. If progression during other experimental therapy is confirmed the time interval between previous treatment and BORTEM-17 may be reduced to 4 weeks\n- Eligibility for standard therapy with Temozolomid as 5-days treatment q4w.\n- Negative pregnancy test no longer than 14 days prior to enrollment\n- Women of childbearing potential (WOCBP) defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile must use adequate contraception. Permanent sterilization methods include hysterectomy, bilateral salpingectomy or bilateral oophorectomy\n- Men in sexual relationship with WOCBP must agree to use a condom during treatment and until 3 months after the last dose of bortezomib and 6 months after the last dose of TMZ\n- Must submit an unstained paraffin block and/or cryopreserved tumour tissue from surgical procedure\n- Must be >- 18 years old, with a life expectancy > 8 weeks\n- Radiologically (MRI) confirmed tumour relapse/progression ≥ 12 weeks since completed radiotherapy\n- Measurable recurrent tumour\n- Tumour not available for radiosurgery\n- Patients previously treated with radiosurgery er eligible for the study\n- If previously treated with gammaknife, at least one evaluable lesion outside the irradiated area is required, unless the time after the radiosurgery is 12 weeks or more"}

Exclusion criteria

• {"criterion_text":"- Hypersensitivity to Bortezomib, boron, or mannitol\n- Electrocardiographic evidence of acute ischemia or active conduction system abnormalities\n- Serious medical or psychiatric illness that would interfere with study participation including, but not limited to, any of the following: - 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\n- 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\n- Disease that will obscure toxicity or dangerously alter drug metabolism\n- Viral hepatitis (HBV surface antigen positive) or active hepatitis C infection\n- Concurrent investigational drugs (chemotherapy) must be stopped at least 12 weeks prior to therapy or treatment failure under other experimental therapy must be confirmed before study entry. If progression during previous experimental therapy is confirmed the time interval before BORTEM-17 study entry may be reduced to 6 weeks.\n- Concurrent use of any inducers of CYP450 3A4 including, but not limited to enzyme-inducing anti-epileptic drugs [EIAED] e.g. phenytoin, fosphenytoin, carbamazepine, phenobarbital, or primidone.\n- Another ongoing experimental therapy\n- Any contraindications for use of Temozolomid\n- Peripheral neuropathy ≥ grade 2\n- Previous treatment with bevacizumab or lomustine either as monotherapy or in combination with procarbazine and vincristine for ralapsed glioblastoma (PCV as primary treatment of low grade oligodendroglioma, before development of glioblastoma is allowed)\n- Myocardial infarction within the past 6 months\n- NYHA class III or IV heart failure\n- Uncontrolled angina\n- Severe uncontrolled ventricular arrhythmias\n- Known heart failure"}

Primary endpoints

• {"endpoint_text":"- Phase IB of the trial: Assessment of safety and tolerability of Bortezomib administered with Temozolomide.","definition_or_measurement_approach":"Safety and tolerability assessment (no further measurement details provided in listed primary endpoint text)."}
• {"endpoint_text":"- Phase II: Assessment of efficacy of Temozolomide administered together with Bortezomib in recurrent glioblastoma. Overall survival (OS) at 1 year. Median OS from the 1st relapse. Progression free survival at 6 months. Median PFS from the 1st relapse. Time to progression.","definition_or_measurement_approach":"Efficacy measured by Overall survival (OS) at 1 year, median OS from 1st relapse, progression-free survival (PFS) at 6 months, median PFS from 1st relapse, and time to progression as specified in the endpoint text."}

Secondary endpoints

• {"endpoint_text":"- Tumour response as assessed by contrast enhanced MRI using RANO criteria and neurological exam, [Time Frame: MRI at start of treatment and every 12th week, neurologic exam every 4 weeks]. If disease progression is suspected according to NANO criteria (clinical assessment) further confirmation with MRI (RANO) is required.","definition_or_measurement_approach":"Tumour response assessed by contrast-enhanced MRI using RANO criteria; MRI at baseline and every 12 weeks; neurologic exam every 4 weeks; confirmation with MRI (RANO) if progression suspected by NANO."}
• {"endpoint_text":"- Neurologic assessment according to NANO criteria [Time Frame: neurologic exam every 4 weeks]","definition_or_measurement_approach":"Neurologic function assessed using NANO criteria with neurologic exams every 4 weeks."}
• {"endpoint_text":"- Identification of novel tumor biomarkers by determining physiological, molecular and biochemical changes in blood and tumor tissue that correlate with treatment responses","definition_or_measurement_approach":"Biomarker identification through analysis of physiological, molecular and biochemical changes in blood and tumour tissue correlated with treatment responses (no additional procedural detail provided)."}

Norway

Earliest CTIS Part Ii Submission Date

24-09-2024

Latest Decision Or Authorization Date

05-02-2026

Processing Time Days

499

Number Of Sites

4

Number Of Participants

63

Primary sponsor

Full Name

Helse Bergen HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway