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

• ClinicalTrials.gov Identifier: NCT03776071
• Recruitment Status: Not yet recruiting
• First Posted: December 14, 2018
• Last Update Posted: May 8, 2019
• Sponsor: Denovo Biopharma LLC
• Information provided by (Responsible Party): Denovo Biopharma LLC

Tracking Information

• First Submitted Date: December 12, 2018
• First Posted Date: December 14, 2018
• Last Update Posted Date: May 8, 2019
• Estimated Study Start Date: June 2019
• Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 13, 2018): Overall Survival [ Time Frame: Up to 3 years ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03776071 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Glioblastoma

Intervention

• Drug: Enzastaurin Hydrochloride
  mg
  Other Name: Kinenza
• Other: Placebo
  mg
• Drug: Temozolomide
  mg/m^2
  Other Name: Temodar
• Radiation: Radiotherapy
  Gy

Study Arms

• 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

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: December 13, 2018): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Lei Zhang; 858.410.0262; lzhang@denovobiopharma.com

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT03776071
• Other Study ID Numbers: 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: Not Provided
• Responsible Party: Denovo Biopharma LLC
• Study Sponsor: Denovo Biopharma LLC
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Denovo Biopharma LLC
• Verification Date: December 2018