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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

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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

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.

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: Enzastaurin Hydrochloride Other: Placebo Drug: Temozolomide Radiation: Radiotherapy Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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)
Drug: Enzastaurin Hydrochloride
mg
Other Name: Kinenza

Drug: Temozolomide
mg/m^2
Other Name: Temodar

Radiation: Radiotherapy
Gy

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
Other: Placebo
mg

Drug: Temozolomide
mg/m^2
Other Name: Temodar

Radiation: Radiotherapy
Gy




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: Up to 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03776071


Contacts
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Contact: Lei Zhang 858.410.0262 lzhang@denovobiopharma.com

Sponsors and Collaborators
Denovo Biopharma LLC

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Responsible Party: Denovo Biopharma LLC
ClinicalTrials.gov Identifier: NCT03776071     History of Changes
Other Study ID Numbers: DB102-201
First Posted: December 14, 2018    Key Record Dates
Last Update Posted: May 8, 2019
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents