Skip to main content

A Trial of Enzastaurin Plus Temozolomide During and Following Radiation Therapy in Patients With Newly Diagnosed Glioblastoma With or Without the Novel Genomic Biomarker, DGM1

Trial Status: Active

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.

Inclusion Criteria

  • Signed informed consent
  • Age ≥ 18 years with life expectancy > 12 weeks
  • Histologically proven, newly diagnosed supratentorial glioblastoma based on the World Health Organization (WHO) classification (2016); prior diagnosis of lower grade astrocytoma that has been upgraded to histologically confirmed glioblastoma is eligible if chemotherapy and radiotherapy treatment-naïve
  • Randomization must occur within 5 weeks of resection (subjects undergoing biopsy only are excluded)
  • Craniotomy site must be adequately healed, free of drainage or cellulitis and the underlying cranioplasty must appear intact prior to start of study treatment
  • Available and willing to submit sufficient and of adequate quality tumor tissue representative of glioblastoma to perform MGMT promoter methylation status testing
  • Karnofsky performance status (KPS) ≥ 60
  • Stable or decreasing corticosteroids within 5 days prior to study treatment start
  • Willing to forego the use of Tumor Treating Fields therapy (Optune®)
  • Adequate organ function within 14 days prior to randomization: Bone marrow
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
  • Platelets count ≥ 100 x 109/L;
  • Hemoglobin ≥ 10 g/dL (eligibility level for hemoglobin may be met by transfusion) Renal a. Serum creatinine < 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min as calculated using the method standard for the institution Hepatic
  • Total serum bilirubin ≤ 2 x ULN unless the patient has documented Gilbert syndrome;
  • Aspartate and alanine transaminase (AST/SGOT and ALT/SGPT) ≤ 2.5 x ULN; ≤ 5.0 x ULN if there is liver involvement secondary to tumor;
  • Alkaline phosphatase (ALP) ≤ 2.5 x ULN; ≤ 5 x ULN in case of bone metastasis
  • Negative serum pregnancy test (for females of childbearing potential) within 14 days prior to randomization
  • Male and female subjects of reproductive potential must agree to use an effective method of contraception (e.g., oral contraceptives, intrauterine device, barrier method) throughout the study and for at least 3 months after the last dose of study treatment
  • Men are considered of reproductive potential unless they have undergone a vasectomy and confirmed sterile by a post-vasectomy semen analysis
  • 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
  • Willing and able to comply with protocol

Exclusion Criteria

  • Unable to swallow tablets or capsules
  • Pregnant or breastfeeding
  • Prior chemotherapy (including carmustine-containing wafers (Gliadel®), immunotherapy (including vaccine therapy)) or investigation agent 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)
  • Prior radiotherapy to the brain
  • Unable to discontinue use of EIAEDs, if previously taking EIAEDs, must have been discontinued ≥ 2 weeks prior to randomization
  • Use of a strong inducer or moderate or strong inhibitor of CYP3A4 within 7 days prior to randomization or expected requirement for use on study therapy
  • Use of any medication that can prolong the QT/QTc interval within 7 days prior to randomization or expected requirement for use on study therapy
  • Active bacterial, fungal or viral infection requiring systemic treatment
  • Personal or immediate family history of long QT syndrome, QTc interval > 450 msec (males) or > 470 msec (females) at screening (recommended that QTc be calculated using Fridericia correction formula, QTcF), or a history of unexplained syncope
  • Any contraindication to temozolomide listed in the local product label
  • Another malignancy except adequately treated non-melanoma skin cancer; subjects who have had another malignancy in the past, but have been disease-free for more than 5 years, and subjects who have had a localized malignancy treated with curative intent and disease free for more than 2 years are eligible
  • Participation in other studies involving investigational drug(s) within 30 days prior to randomization
  • 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

California

Duarte
City of Hope Comprehensive Cancer Center
Status: APPROVED
Orange
UC Irvine Health / Chao Family Comprehensive Cancer Center
Status: ACTIVE
San Diego
University of California San Diego
Status: ACTIVE
San Francisco
University of California San Francisco
Status: ACTIVE
Contact: UCSF Clinical Trials
Phone: 877-827-3222

Colorado

Aurora
University of Colorado Hospital
Status: APPROVED

Florida

Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: ACTIVE

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: APPROVED
Contact: Elizabeth Catherine Neil
Phone: 952-993-1517
Email: neile@umn.edu

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: IN_REVIEW
Winston-Salem
Wake Forest University Health Sciences
Status: ACTIVE

Ohio

Columbus
Ohio State University Comprehensive Cancer Center
Status: APPROVED

Texas

San Antonio
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
Status: IN_REVIEW
Contact: Sonia Lisa Creighton
Phone: 210-450-1366

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: ACTIVE

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: IN_REVIEW

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Denovo Biopharma LLC

  • Primary ID DB102-01
  • Secondary IDs NCI-2020-13730
  • Clinicaltrials.gov ID NCT03776071