Clinical Trials /

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

NCT03776071

Description:

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.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: DB102-01
  • NCT ID: NCT03776071

Conditions

  • Glioblastoma

Interventions

DrugSynonymsArms
Enzastaurin HydrochlorideKinenzaRT plus TMZ and ENZ; ENZ alone; TMZ and ENZ
TemozolomideTemodarRT plus TMZ and ENZ; ENZ alone; TMZ and ENZ

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
RT plus TMZ and ENZ; ENZ alone; TMZ and ENZActive ComparatorRadiotherapy (RT) plus temozolomide (TMZ) and enzastaurin (ENZ) (Concurrent Phase) followed by enzastaurin alone (Single-Agent Phase), then temozolomide and enzastaurin (Adjuvant Phase)
  • Enzastaurin Hydrochloride
  • Temozolomide
RT plus TMZ and placebo; placebo; TMZ and placeboPlacebo ComparatorRadiotherapy (RT) plus temozolomide (TMZ) and placebo followed placebo then by temozolomide and placebo
  • Temozolomide

Eligibility Criteria

        Inclusion Criteria:

          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 5 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. Available and willing to submit sufficient and of adequate quality tumor tissue
             representative of glioblastoma to perform MGMT promoter methylation status testing

          7. Karnofsky performance status (KPS) ≥ 60

          8. Stable or decreasing corticosteroids within 5 days prior to study treatment start

          9. Willing to forego the use of Tumor Treating Fields therapy (Optune®)

         10. 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

             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

               1. Total serum bilirubin ≤ 2 x ULN unless the patient has documented Gilbert
                  syndrome;

               2. 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;

               3. Alkaline phosphatase (ALP) ≤ 2.5 x ULN; ≤ 5 x ULN in case of bone metastasis

         11. Negative serum pregnancy test (for females of childbearing potential) within 14 days
             prior to randomization

         12. 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

         13. Willing and able to comply with protocol

        Exclusion Criteria:

          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. Prior radiotherapy to the brain

          5. Unable to discontinue use of EIAEDs, if previously taking EIAEDs, must have been
             discontinued ≥ 2 weeks prior to randomization

          6. 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

          7. 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

          8. Active bacterial, fungal or viral infection requiring systemic treatment

          9. 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

         10. Any contraindication to temozolomide listed in the local product label

         11. 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

         12. Participation in other studies involving investigational drug(s) within 30 days prior
             to randomization

         13. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival
Time Frame:Up to 3 years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Denovo Biopharma LLC

Last Updated

January 8, 2021