Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Diego, California and other locations
Dates
study started
estimated completion

Description

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.

Official Title

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Enzastaurin Added to Temozolomide During and Following Radiation Therapy in Newly Diagnosed Glioblastoma Patients Who Possess the Novel Genomic Biomarker DGM1

Keywords

Glioblastoma Temozolomide Enzastaurin Hydrochloride Radiotherapy RT plus TMZ and ENZ; ENZ alone; TMZ and ENZ

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Signed informed consent
  2. Age ≥ 18 years with life expectancy > 12 weeks
  3. 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
  4. Randomization must occur within 6 weeks of resection (subjects undergoing biopsy only are excluded)
  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. Available and willing to submit sufficient and of adequate quality tumor tissue representative of glioblastoma to perform MGMT promoter methylation status testing
  8. Karnofsky performance status (KPS) ≥ 70
  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. Platelets count ≥ 100 x 10⁹/L;
  3. Hemoglobin ≥ 10 g/dL (eligibility level for hemoglobin may be met by transfusion)

Renal

  1. 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 (e.g. Cockcroft-Gault or MDRD method)

Hepatic

  1. Total serum bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert syndrome;
  2. Aspartate and alanine transaminase (AST/SGOT and ALT/SGPT) ≤ 2.5 x ULN
  3. Alkaline phosphatase (ALP) ≤ 2.5 x ULN
  4. . Negative serum pregnancy test (for females of childbearing potential) within 7 days prior to the first study treatment
  5. . 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, or 6 months for female subjects in regard to the last dose of temozolimide (TMZ), whichever is later
  6. Men are considered of reproductive potential unless they have undergone a vasectomy and confirmed sterile by a post-vasectomy semen analysis
  7. 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
  8. . Willing and able to comply with protocol

You CAN'T join if...

  1. Unable to swallow tablets or capsules
  2. Pregnant or breastfeeding
  3. 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)
  4. Glioblastoma IDH mutant
  5. Prior radiotherapy to the brain
  6. Unable to discontinue use of enzyme-inducing anti-epileptic drugs (EIAEDs), 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 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 within 7 days prior to randomization or expected requirement for use on study therapy
  10. . Active bacterial, fungal or viral infection requiring systemic treatment
  11. . Personal or 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
  12. . Any contraindication to temozolomide listed in the local product label
  13. . 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
  14. . Participation in other studies involving investigational drug(s) within 30 days prior to randomization
  15. . 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

Locations

  • University of California San Diego Moores Cancer Center accepting new patients
    San Diego California 92037 United States
  • University of California Irvine Health Chao Family Comprehensive Cancer Center accepting new patients
    Orange California 92868 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Denovo Biopharma LLC
ID
NCT03776071
Phase
Phase 3
Study Type
Interventional
Last Updated