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 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: DB102-01
• Study Type: interventional
• Target: 260
• Locations: 3 countries
• Sites: 65

Brief Summary

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.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Up to 3 years

Study Arms (2)

RT plus TMZ and ENZ; ENZ alone; TMZ and ENZ

ACTIVE COMPARATOR

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; Drug: Temozolomide; Radiation: Radiotherapy

RT plus TMZ and placebo; placebo; TMZ and placebo

PLACEBO COMPARATOR

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

Other: Placebo; Drug: Temozolomide; Radiation: Radiotherapy

Interventions

Enzastaurin Hydrochloride DRUG

mg

Also known as: Kinenza

RT plus TMZ and ENZ; ENZ alone; TMZ and ENZ

Placebo OTHER

mg

RT plus TMZ and placebo; placebo; TMZ and placebo

Temozolomide DRUG

mg/m\^2

Also known as: Temodar

RT plus TMZ and ENZ; ENZ alone; TMZ and ENZ; RT plus TMZ and placebo; placebo; TMZ and placebo

Radiotherapy RADIATION

Gy

RT plus TMZ and ENZ; ENZ alone; TMZ and ENZ; RT plus TMZ and placebo; placebo; TMZ and placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Age ≥ 18 years with life expectancy \> 12 weeks
• 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
• Randomization must occur within approximately 6 weeks after resection (patients undergoing biopsy only are excluded from the study)
• Craniotomy site must be adequately healed, free of drainage or cellulitis and the underlying cranioplasty must appear intact prior to start of study treatment
• DGM1 biomarker status (positive or negative) is available prior to randomization
• Availability of tumor tissue representative of glioblastoma from surgery, and MGMT promoter methylation status is determined prior to study randomization
• Karnofsky performance status (KPS) ≥ 70 (Appendix 1)
• Stable or decreasing corticosteroids within 5 days prior to study treatment start
• Willing to forego the use of Tumor Treating Fields therapy (Optune®)
• Adequate organ function within 14 days prior to randomization:
• Bone marrow
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
• Platelet count ≥ 100 x 109/L;
• Hemoglobin ≥ 10 g/dL (eligibility level for hemoglobin may be met by transfusion) Renal

You may not qualify if:

• Patients with any of the following characteristics/conditions will be excluded from study:
• Unable to swallow tablets or capsules
• Pregnant or breastfeeding
• 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)
• Glioblastoma IDH mutant
• Prior radiation therapy to the brain
• 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
• 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
• Use of warfarin that cannot be stopped prior to the study.
• 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
• Active bacterial, fungal or viral infection requiring systemic treatment
• 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
• 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)
• 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)
• Persistent electrolyte abnormalities such as hypokalemia or hypomagnesemia that do not respond to treatment

Sponsors & Collaborators

• Denovo Biopharma LLC: lead

Study Sites (65)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Mayo Clinic - Arizona

Scottsdale, Arizona, 85259, United States

Location

City of Hope Comprehensive Cancer Center - Duarte

Duarte, California, 91010, United States

Location

University of California San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California Irvine Health Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

The University of Southern California

Pasadena, California, 91105, United States

Location

University of California San Francisco Helen Diller Family Comprehensive CA Ctr

San Francisco, California, 94143, United States

Location

University of Colorado Hospital Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Blue Sky Neurology

Englewood, Colorado, 80220, United States

Location

Smilow Cancer Hospital - New Haven

New Haven, Connecticut, 06511, United States

Location

Lynn Cancer Institute

Boca Raton, Florida, 33486, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224-1865, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Norton Cancer Institute - Multidisciplinary Clinic

Louisville, Kentucky, 40202, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

John Nasseff Neuroscience Institute

Minneapolis, Minnesota, 55407, United States

Location

Masonic Cancer Center

Minneapolis, Minnesota, 55455-4800, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine Center for Advanced Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack Meridian Health - JFK Medical Center

Edison, New Jersey, 08820, United States

Location

New York University Medical Oncology Associates

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

New York - Presbyterian - Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Messino Cancer Centers

Asheville, North Carolina, 28806, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7055, United States

Location

Wake Forest Baptist Health - Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

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

Columbus, Ohio, 43210, United States

Location

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Penn Medicine - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

SCRI - Tennessee Oncology - Nashville - Centennial

Nashville, Tennessee, 37203-1625, United States

Location

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Austin Cancer Center - Park St. David's

Austin, Texas, 78705, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Lynn Cancer Institute

Houston, Texas, 77030, United States

Location

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

Houston, Texas, 77030, United States

Location

Mays Cancer Center

San Antonio, Texas, 78229, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109--1023, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

British Columbia Cancer Agency - Abbotsford

Abbotsford, British Columbia, V2S OC2, Canada

Location

British Columbia Cancer Agency - Victoria

Victoria, British Columbia, V8R 6V5, Canada

Location

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Hôpital Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Saskatoon Cancer Center

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

First Affiliated Hospital of USTC - Anhui Provincial Hospital

Hefei, Anhui, 230071, China

Location

Beijing Tian Tan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

Location

Sanbo Brain Hospital, Capital Medical University

Beijing, Beijing Municipality, 100093, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Shenzhen Second People's Hospital

Shenzhen, Guangdong, 518035, China

Location

Tongji Hospital

Wuhan, Hubei, 430030, China

Location

Shengjing Hospital - Nanhu Campus

Shenyang, Liaoning, 110004, China

Location

Tangdu Hospital

Xi'an, Shaanxi, 710038, China

Location

Huashan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

General Hospital of Tianjin Medical University

Tianjin, Tianjin Municipality, 300052, China

Location

Tianjin Huanhu Hospital

Xianshuigu, Tianjin Municipality, 300350, China

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2018
• First Posted: December 14, 2018
• Study Start: December 16, 2020
• Primary Completion: February 29, 2024
• Study Completion: February 29, 2024
• Last Updated: April 22, 2024

Record last verified: 2024-04

Locations

CN (12); US (47); CA (6)