Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This study will be conducted as a randomized, double-blind, placebo-controlled, multi-center
Phase 3 study. Approximately 300 subjects with newly diagnosed glioblastoma who meet all
eligibility criteria will be enrolled.
Phase
Phase 3
Funding Agency/Sponsor
Industrial
Disease
Neurological Cancer
Enrollment Eligibility
Patient Inclusion Criteria:
Patients must meet all the following inclusion criteria to be eligible for enrollment into
the study:
1. Signed informed consent
2. Age ≥ 18 years with life expectancy > 12 weeks
3. Histologically proven, newly diagnosed supratentorial glioblastoma (IDH mutant is
excluded) based on the WHO classification (2016) which includes gliosarcoma (GS);
prior diagnosis of lower grade astrocytoma that has been upgraded to histologically
confirmed glioblastoma is eligible if chemotherapy and radiation therapy
treatment-naïve
4. Randomization must occur within approximately 6 weeks after resection (patients
undergoing biopsy only are excluded from the study)
5. Craniotomy site must be adequately healed, free of drainage or cellulitis and the
underlying cranioplasty must appear intact prior to start of study treatment
6. DGM1 biomarker status (positive or negative) is available prior to randomization
7. Availability of tumor tissue representative of glioblastoma from surgery, and MGMT
promoter methylation status is determined prior to study randomization
8. Karnofsky performance status (KPS) ≥ 70 (Appendix 1)
9. Stable or decreasing corticosteroids within 5 days prior to study treatment start
10. Willing to forego the use of Tumor Treating Fields therapy (Optune®)
11. Adequate organ function within 14 days prior to randomization:
Bone marrow
1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
2. Platelet count ≥ 100 x 109/L;
3. Hemoglobin ≥ 10 g/dL (eligibility level for hemoglobin may be met by transfusion)
Renal
4. Serum creatinine < 1.5 x upper limit of normal (ULN) or calculated creatinine
clearance ≥ 60 mL/min as calculated using an appropriately validated prediction
equation for the estimation of eGFR (eg, Cockcroft-Gault or MDRD method).
Hepatic
5. Total serum bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert
syndrome;
6. Aspartate and Alanine transaminase (AST/SGOT and ALT/SGPT) ≤ 2.5 x ULN;
7. Alkaline phosphatase (ALP) ≤ 2.5 x ULN
12. Negative serum pregnancy test (for females of childbearing potential) within 7 days
prior to the first study treatment
13. Male and female patients of reproductive potential must agree to use an effective
method of contraception (eg, oral contraceptives, intrauterine device, barrier method)
throughout the study and for at least 3 months after the last dose of study treatment,
or 6 months for female patients in regard to the last dose of temozolomide (TMZ),
whichever is later
- Men are considered of reproductive potential unless they have undergone a
vasectomy and confirmed sterile by a post-vasectomy semen analysis
- Male patients must agree not to donate their semen during treatment with
temozolomide and for at least 6 months after their last dose of temozolomide
- Women are considered of reproductive potential unless they have undergone
hysterectomy and/or surgical sterilization (at least 6 weeks following a
bilateral oophorectomy, bilateral tubal ligation, or bilateral tubal occlusive
procedure that has been confirmed in accordance with the device's label), have
medically confirmed ovarian failure, or achieved postmenopausal status (defined
as cessation of regular menses for at least 12 consecutive months with no
alternative pathological or physiological cause; status may be confirmed by
having a serum follicle-stimulating hormone (FSH) level within the laboratory's
reference range for postmenopausal women
14. Willing and able to comply with the protocol
Patient Exclusion Criteria:
Patients with any of the following characteristics/conditions will be excluded from study:
1. Unable to swallow tablets or capsules
2. Pregnant or breastfeeding
3. Prior chemotherapy (including carmustine-containing wafers (Gliadel®), immunotherapy
(including vaccine therapy), or investigational products for GBM or GS (previous
5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) administered prior to
surgery to aid in optimal surgical resection is permitted)
4. Glioblastoma IDH mutant
5. Prior radiation therapy to the brain
6. Unable to discontinue use of enzyme-inducing anti-epileptic drugs (EIAEDs), see
Section 5.1.2.4.1; if previously taking EIAEDs, must have been discontinued ≥ 2 weeks
prior to randomization
7. Use of a strong inducer or moderate or strong inhibitor of CYP3A4 (Appendix 2) within
7 days prior to randomization or expected requirement for use on study therapy
8. Use of warfarin that cannot be stopped prior to the study.
9. Use of any medication that can prolong the QT/QTc interval (Appendix 3) within 7 days
prior to start of study therapy, or plan to use such a medication during the study
10. Active bacterial, fungal or viral infection requiring systemic treatment
11. Personal or family history of abnormal long QT interval, QTc interval > 450 msec
(males) or > 470 msec (females) as read on the printout of the electrocardiogram (ECG)
at screening (recommended that QTc be calculated using Fridericia's correction
formula, QTcF: see Section 7.3.2.2), or a history of unexplained syncope
12. Unstable angina; myocardial infarction or coronary artery bypass graft/percutaneous
stent placement within 6 months of starting study treatment, congestive heart failure
requiring treatment (New York Heart Association [NYHA] Grade ≥2)
13. History of significant cardiac arrhythmia (ventricular tachycardia or fibrillation,
Torsades de Pointe) or second- or third-degree A-V block, symptomatic bradycardia
(unless controlled with a pacemaker)
14. Persistent electrolyte abnormalities such as hypokalemia or hypomagnesemia that do not
respond to treatment
15. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency
syndrome (AIDS)
16. Evidence of chronic hepatitis C infection as indicated by antibody to hepatitis C
virus (HCV) with positive HCV ribonucleic acid (RNA)
17. Evidence of active or chronic hepatitis B infection as indicated by either:
hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb)
positive with hepatitis B virus-deoxyribonucleic acid (HBV-DNA) positive (any
detectable amount is considered positive)
18. Any contraindication to temozolomide listed in the local product label
19. Another malignancy except adequately treated non-melanoma skin cancer; patients who
have had another primary malignancy in the past, but have been disease-free for more
than 5 years, and patients who have had a localized malignancy treated with curative
intent and disease free for more than 2 years are eligible
20. Participation in other studies involving investigational product(s) within 30 days
prior to randomization
21. Other severe acute or chronic medical or psychiatric condition, including recent
(within the past year) or active suicidal ideation or behavior, or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation of
study results and, in the judgment of the investigator, would make the patient
inappropriate for participation in this study