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

NCT ID: NCT03776071

Last Updated: 2024-04-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

260 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-16

Study Completion Date

2024-02-29

Brief Summary

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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.

Detailed Description

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Conditions

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Glioblastoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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)

Group Type ACTIVE_COMPARATOR

Enzastaurin Hydrochloride

Intervention Type DRUG

mg

Temozolomide

Intervention Type DRUG

mg/m\^2

Radiotherapy

Intervention Type RADIATION

Gy

RT plus TMZ and placebo; placebo; TMZ and placebo

Radiotherapy (RT) plus temozolomide (TMZ) and placebo followed placebo then by temozolomide and placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

mg

Temozolomide

Intervention Type DRUG

mg/m\^2

Radiotherapy

Intervention Type RADIATION

Gy

Interventions

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Enzastaurin Hydrochloride

mg

Intervention Type DRUG

Placebo

mg

Intervention Type OTHER

Temozolomide

mg/m\^2

Intervention Type DRUG

Radiotherapy

Gy

Intervention Type RADIATION

Other Intervention Names

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Kinenza Temodar

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent
2. Age ≥ 18 years with life expectancy \> 12 weeks
3. Histologically proven, newly diagnosed supratentorial glioblastoma (IDH mutant is excluded) based on the WHO classification (2016) which includes gliosarcoma (GS); prior diagnosis of lower grade astrocytoma that has been upgraded to histologically confirmed glioblastoma is eligible if chemotherapy and radiation therapy treatment-naïve
4. Randomization must occur within approximately 6 weeks after resection (patients undergoing biopsy only are excluded from the study)
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. Availability of tumor tissue representative of glioblastoma from surgery, and MGMT promoter methylation status is determined prior to study randomization
8. Karnofsky performance status (KPS) ≥ 70 (Appendix 1)
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. Platelet count ≥ 100 x 109/L;
3. Hemoglobin ≥ 10 g/dL (eligibility level for hemoglobin may be met by transfusion) Renal
4. 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 (eg, Cockcroft-Gault or MDRD method).

Hepatic
5. Total serum bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert syndrome;
6. Aspartate and Alanine transaminase (AST/SGOT and ALT/SGPT) ≤ 2.5 x ULN;
7. Alkaline phosphatase (ALP) ≤ 2.5 x ULN
12. Negative serum pregnancy test (for females of childbearing potential) within 7 days prior to the first study treatment
13. Male and female patients of reproductive potential must agree to use an effective method of contraception (eg, 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 patients in regard to the last dose of temozolomide (TMZ), whichever is later

* Men are considered of reproductive potential unless they have undergone a vasectomy and confirmed sterile by a post-vasectomy semen analysis
* Male patients must agree not to donate their semen during treatment with temozolomide and for at least 6 months after their last dose of temozolomide
* 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
14. Willing and able to comply with the protocol

Exclusion Criteria

Patients with any of the following characteristics/conditions will be excluded from study:

1. Unable to swallow tablets or capsules
2. Pregnant or breastfeeding
3. Prior chemotherapy (including carmustine-containing wafers (Gliadel®), immunotherapy (including vaccine therapy), or investigational products 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 radiation therapy to the brain
6. Unable to discontinue use of enzyme-inducing anti-epileptic drugs (EIAEDs), see Section 5.1.2.4.1; 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 (Appendix 2) 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 (Appendix 3) within 7 days prior to start of study therapy, or plan to use such a medication during the study
10. Active bacterial, fungal or viral infection requiring systemic treatment
11. Personal or family history of abnormal long QT interval, QTc interval \> 450 msec (males) or \> 470 msec (females) as read on the printout of the electrocardiogram (ECG) at screening (recommended that QTc be calculated using Fridericia's correction formula, QTcF: see Section 7.3.2.2), or a history of unexplained syncope
12. Unstable angina; myocardial infarction or coronary artery bypass graft/percutaneous stent placement within 6 months of starting study treatment, congestive heart failure requiring treatment (New York Heart Association \[NYHA\] Grade ≥2)
13. History of significant cardiac arrhythmia (ventricular tachycardia or fibrillation, Torsades de Pointe) or second- or third-degree A-V block, symptomatic bradycardia (unless controlled with a pacemaker)
14. Persistent electrolyte abnormalities such as hypokalemia or hypomagnesemia that do not respond to treatment
15. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
16. Evidence of chronic hepatitis C infection as indicated by antibody to hepatitis C virus (HCV) with positive HCV ribonucleic acid (RNA)
17. Evidence of active or chronic hepatitis B infection as indicated by either:

hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb) positive with hepatitis B virus-deoxyribonucleic acid (HBV-DNA) positive (any detectable amount is considered positive)
18. Any contraindication to temozolomide listed in the local product label
19. Another malignancy except adequately treated non-melanoma skin cancer; patients who have had another primary malignancy in the past, but have been disease-free for more than 5 years, and patients who have had a localized malignancy treated with curative intent and disease free for more than 2 years are eligible
20. Participation in other studies involving investigational product(s) within 30 days prior to randomization
21. 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Denovo Biopharma LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Barrow Neurological Institute

Phoenix, Arizona, United States

Site Status

Mayo Clinic - Arizona

Scottsdale, Arizona, United States

Site Status

City of Hope Comprehensive Cancer Center - Duarte

Duarte, California, United States

Site Status

University of California San Diego Moores Cancer Center

La Jolla, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

University of California Irvine Health Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

The University of Southern California

Pasadena, California, United States

Site Status

University of California San Francisco Helen Diller Family Comprehensive CA Ctr

San Francisco, California, United States

Site Status

University of Colorado Hospital Anschutz Cancer Pavilion

Aurora, Colorado, United States

Site Status

Blue Sky Neurology

Englewood, Colorado, United States

Site Status

Smilow Cancer Hospital - New Haven

New Haven, Connecticut, United States

Site Status

Lynn Cancer Institute

Boca Raton, Florida, United States

Site Status

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Miami Cancer Institute

Miami, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Kentucky Markey Cancer Center

Lexington, Kentucky, United States

Site Status

Norton Cancer Institute - Multidisciplinary Clinic

Louisville, Kentucky, United States

Site Status

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

John Nasseff Neuroscience Institute

Minneapolis, Minnesota, United States

Site Status

Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine Center for Advanced Medicine

St Louis, Missouri, United States

Site Status

Hackensack Meridian Health - JFK Medical Center

Edison, New Jersey, United States

Site Status

New York University Medical Oncology Associates

New York, New York, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

New York - Presbyterian - Weill Cornell Medical Center

New York, New York, United States

Site Status

Messino Cancer Centers

Asheville, North Carolina, United States

Site Status

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Wake Forest Baptist Health - Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status

The Ohio State University - The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

Site Status

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Penn Medicine - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

SCRI - Tennessee Oncology - Nashville - Centennial

Nashville, Tennessee, United States

Site Status

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Austin Cancer Center - Park St. David's

Austin, Texas, United States

Site Status

Baylor University Medical Center

Dallas, Texas, United States

Site Status

Lynn Cancer Institute

Houston, Texas, United States

Site Status

University of Texas Health Science Center at Houston (UT Health)

Houston, Texas, United States

Site Status

Mays Cancer Center

San Antonio, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

British Columbia Cancer Agency - Abbotsford

Abbotsford, British Columbia, Canada

Site Status

British Columbia Cancer Agency - Victoria

Victoria, British Columbia, Canada

Site Status

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Site Status

Hôpital Fleurimont

Sherbrooke, Quebec, Canada

Site Status

Saskatoon Cancer Center

Saskatoon, Saskatchewan, Canada

Site Status

First Affiliated Hospital of USTC - Anhui Provincial Hospital

Hefei, Anhui, China

Site Status

Beijing Tian Tan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status

Sanbo Brain Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China

Site Status

Shenzhen Second People's Hospital

Shenzhen, Guangdong, China

Site Status

Tongji Hospital

Wuhan, Hubei, China

Site Status

Shengjing Hospital - Nanhu Campus

Shenyang, Liaoning, China

Site Status

Tangdu Hospital

Xi'an, Shaanxi, China

Site Status

Huashan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, China

Site Status

General Hospital of Tianjin Medical University

Tianjin, Tianjin Municipality, China

Site Status

Tianjin Huanhu Hospital

Xianshuigu, Tianjin Municipality, China

Site Status

Countries

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United States Canada China

Other Identifiers

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DB102-01

Identifier Type: -

Identifier Source: org_study_id

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