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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03776071
Recruitment Status : Not yet recruiting
First Posted : December 14, 2018
Last Update Posted : May 8, 2019
Sponsor:
Information provided by (Responsible Party):
Denovo Biopharma LLC

Tracking Information
First Submitted Date  ICMJE December 12, 2018
First Posted Date  ICMJE December 14, 2018
Last Update Posted Date May 8, 2019
Estimated Study Start Date  ICMJE June 2019
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 13, 2018)
Overall Survival [ Time Frame: Up to 3 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03776071 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE A Phase 2b Trial of Enzastaurin Plus Temozolomide During and Following Radiation Therapy in Patients With Newly Diagnosed Glioblastoma With or Without the Novel Genomic Biomarker, DGM1
Brief Summary This study will be conducted as a randomized, double-blind, placebo controlled, multi-center Phase 2b study. Approximately 200 subjects with newly diagnosed glioblastoma who meet all eligibility criteria will be enrolled.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE
  • Drug: Enzastaurin Hydrochloride
    mg
    Other Name: Kinenza
  • Other: Placebo
    mg
  • Drug: Temozolomide
    mg/m^2
    Other Name: Temodar
  • Radiation: Radiotherapy
    Gy
Study Arms  ICMJE
  • Active Comparator: RT plus TMZ and ENZ; ENZ alone; TMZ and ENZ
    Radiotherapy (RT) plus temozolomide (TMZ) and enzastaurin (ENZ) (Concurrent Phase) followed by enzastaurin alone (Single-Agent Phase), then temozolomide and enzastaurin (Adjuvant Phase)
    Interventions:
    • Drug: Enzastaurin Hydrochloride
    • Drug: Temozolomide
    • Radiation: Radiotherapy
  • Placebo Comparator: RT plus TMZ and placebo; placebo; TMZ and placebo
    Radiotherapy (RT) plus temozolomide (TMZ) and placebo followed placebo then by temozolomide and placebo
    Interventions:
    • Other: Placebo
    • Drug: Temozolomide
    • Radiation: Radiotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: December 13, 2018)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lei Zhang 858.410.0262 lzhang@denovobiopharma.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03776071
Other Study ID Numbers  ICMJE DB102-201
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Denovo Biopharma LLC
Study Sponsor  ICMJE Denovo Biopharma LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Denovo Biopharma LLC
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP