Pre-treatment with Bortezsomib to increase the effect of Temozolomide in patients with recurrent glioblastoma

Phase 1

• Conditions: recurrent or progressed WHO grade IV intracranial glioblastoma; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001690-16-NO
• Lead Sponsor: Helse Bergen HF

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-01-29
• Last Update Posted: 18 August 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 63

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) < 1.4.
?Haemoglobin = 10 g/dL (transfusion allowed)
?Bilirubin < 2.5 times upper limit of normal (ULN)
?Serum aspartate aminotransferase (AST); < 2.5 times ULN
?Adequate hepatic function: serum bilirubin = 1.5 x ULN, AST, ALT and alkaline phosphatase = 2.5 ULN,
?Serum potassium within normal limit
?Serum creatinine < 1.5 mg/dL
?Estimated GFR = 60
?Stable doses of corticosteroids for at least 1 week prior to enrolment, but analgesics and other drugs to treat symptoms or prevent complications allowed
?Patients receiving EIAED must be transitioned to non-EIAED at least 2 weeks before study inclusion
?Unfractionated and/or low molecular weight heparin is allowed
?Other investigational drugs must be discontinued at least 12 weeks prior to study entry
?Eligibility for standard therapy with Temozolomid as 5-days treatment q4w.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 58
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified