A Phase III Trial of Marizomib in Patients With Newly Diagnosed Glioblastoma
Marizomib is naturally occurring chemical compound, isolated from marine bacteria. This intravenously administered drug binds to and inhibits a certain protein complex involved in degradation of unneeded or damaged proteins. The subsequent abnormal accumulation of proteins is thought to inhibit tumor cell growth by signaling to the cell to stop dividing and undergo cell death.
Previous studies have established marizomib as a safe addition to the standard treatment for glioblastoma, which involves concurrent TMZ and radiation therapy followed by adjuvant (or additional cycles of) TMZ. This phase III study will assess the efficacy of marizomib in combination with TMZ and radiation therapy, compared to TMZ and radiation therapy alone.
Eligible participants will be randomly assigned to one of the following groups:
- Marizomib + TMZ + Radiation Therapy, followed by adjuvant Marizomib + TMZ
- TMZ + Radiation Therapy, followed by adjuvant TMZ
- Histologically confirmed newly diagnosed glioblastoma (WHO grade IV)
- Tumor resection (gross total or partial), or biopsy only
- Availability of FFPE tumor block or 24 unstained slides for MGMT analysis
- Patient must be eligible for standard TMZ/RT + TMZ
- Karnofsky performance score (KPS) ≥ 70
- Recovered from effects of surgery, postoperative infection and other complications of surgery (if any)
- The patient is at least 18 years of age on day of signing informed consent
- Stable or decreasing dose of steroids for at least 1 week prior to inclusion
- The patient has a life expectancy of at least 3 months
- Patient has undergone a brain MRI within 14 days of randomization but after intervention (resection or biopsy)
- The patient shows adequate organ functions as assessed by the specified laboratory values within 2 weeks prior to randomization defined as adequate bone marrow, renal and hepatic function within the following ranges:
- WBC ≥ 3×10*9/L
- ANC ≥ 1.5×10*9/L
- Platelet count of ≥ 100×10*9/L independent of transfusion
- Hemoglobin ≥ 10 g/dl
- Total Bilirubin ≤ 1.5 ULN
- ALT, AST, alkaline phosphatase (ALP) ≤ 2.5 × ULN
- Serum creatinine < 1.5 x ULN or creatinine clearance (CrCl) > 30 mL/min(using the Cockcroft-Gault formula)
- Women of child bearing potential (WOCBP) must have a negative urine or serum pregnancy test within 7 days prior to the first dose of study treatment.
- Patients of childbearing / reproductive potential must agree to use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1 percent per year) when used consistently and correctly. Patients must also agree not to donate sperm during the study and for 6 months after receiving the last dose of study treatment.
- Women who are breast feeding must agree to discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
- Ability to take oral medication
- Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments.
- Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
For the most up-to-date list of criteria, please visit clinicaltrials.gov.