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

• Sponsor: Denovo Biopharma LLC (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT03776071
• Collaborator: (none)
• Enrollment: 300
• Locations: 65
• Arms: 2
• Anticipated Duration (Months): 53.5
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma	Drug: Enzastaurin Hydrochloride; Other: Placebo; Drug: Temozolomide; Radiation: Radiotherapy	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Enzastaurin Added to Temozolomide During and Following Radiation Therapy in Newly Diagnosed Glioblastoma Patients Who Possess the Novel Genomic Biomarker DGM1
• Actual Study Start Date: Dec 16, 2020
• Anticipated Primary Completion Date: Jun 1, 2025
• Anticipated Study Completion Date: Jun 1, 2025

Arms and Interventions

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 Names: Kinenza ; Drug: Temozolomide; mg/m^2; Other Names: 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 Names: Temodar ; Radiation: Radiotherapy; Gy

Outcome Measures

Primary Outcome Measures

1. Overall Survival [Up to 3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 6 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. DGM1 biomarker status (positive or negative) is available prior to randomization.

7. Available and willing to submit sufficient and of adequate quality tumor tissue representative of glioblastoma to perform MGMT promoter methylation status testing

8. Karnofsky performance status (KPS) ≥ 70

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. Platelets count ≥ 100 x 10⁹/L;

3. Hemoglobin ≥ 10 g/dL (eligibility level for hemoglobin may be met by transfusion)

Renal

1. 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 (e.g. Cockcroft-Gault or MDRD method)

Hepatic

1. Total serum bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert syndrome;

2. Aspartate and alanine transaminase (AST/SGOT and ALT/SGPT) ≤ 2.5 x ULN

3. Alkaline phosphatase (ALP) ≤ 2.5 x ULN

4. Negative serum pregnancy test (for females of childbearing potential) within 7 days prior to the first study treatment

5. 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, or 6 months for female subjects in regard to the last dose of temozolimide (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

• 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

1. 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. Glioblastoma IDH mutant

5. Prior radiotherapy to the brain

6. Unable to discontinue use of enzyme-inducing anti-epileptic drugs (EIAEDs), 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 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 within 7 days prior to randomization or expected requirement for use on study therapy

10. Active bacterial, fungal or viral infection requiring systemic treatment

11. Personal or 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

12. Any contraindication to temozolomide listed in the local product label

13. 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

14. Participation in other studies involving investigational drug(s) within 30 days prior to randomization

15. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Barrow Neurological Institute	Phoenix	Arizona	United States	85013
3	Mayo Clinic - Arizona	Scottsdale	Arizona	United States	85259
4	City of Hope Comprehensive Cancer Center - Duarte	Duarte	California	United States	91010
5	University of California San Diego Moores Cancer Center	La Jolla	California	United States	92093
6	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
7	University of California Irvine Health Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
8	The University of Southern California	Pasadena	California	United States	91105
9	University of California San Francisco Helen Diller Family Comprehensive CA Ctr	San Francisco	California	United States	94143
10	University of Colorado Hospital Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
11	Blue Sky Neurology	Englewood	Colorado	United States	80220
12	Smilow Cancer Hospital - New Haven	New Haven	Connecticut	United States	06511
13	Lynn Cancer Institute	Boca Raton	Florida	United States	33486
14	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224-1865
15	Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
16	Miami Cancer Institute	Miami	Florida	United States	33176
17	Moffitt Cancer Center	Tampa	Florida	United States	33612
18	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
19	Rush University Medical Center	Chicago	Illinois	United States	60612
20	University of Kentucky Markey Cancer Center	Lexington	Kentucky	United States	40536
21	Norton Cancer Institute - Multidisciplinary Clinic	Louisville	Kentucky	United States	40202
22	University of Michigan Rogel Cancer Center	Ann Arbor	Michigan	United States	48109
23	Henry Ford Health System	Detroit	Michigan	United States	48202
24	John Nasseff Neuroscience Institute	Minneapolis	Minnesota	United States	55407
25	Masonic Cancer Center	Minneapolis	Minnesota	United States	55455-4800
26	Mayo Clinic - Rochester	Rochester	Minnesota	United States	55905
27	Washington University School of Medicine Center for Advanced Medicine	Saint Louis	Missouri	United States	63110
28	Hackensack Meridian Health - JFK Medical Center	Edison	New Jersey	United States	08820
29	New York University Medical Oncology Associates	New York	New York	United States	10016
30	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
31	New York - Presbyterian - Weill Cornell Medical Center	New York	New York	United States	10065
32	Messino Cancer Centers	Asheville	North Carolina	United States	28806
33	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7055
34	Wake Forest Baptist Health - Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157
35	The Ohio State University - The James Cancer Hospital and Solove Research Institute	Columbus	Ohio	United States	43210
36	Penn State Health Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
37	Penn Medicine - Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania	United States	19104
38	University of Pittsburgh Medical Center - Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
39	SCRI - Tennessee Oncology - Nashville - Centennial	Nashville	Tennessee	United States	37203-1625
40	Vanderbilt - Ingram Cancer Center	Nashville	Tennessee	United States	37232
41	Austin Cancer Center - Park St. David's	Austin	Texas	United States	78705
42	Baylor University Medical Center	Dallas	Texas	United States	75246
43	Lynn Cancer Institute	Houston	Texas	United States	77030
44	University of Texas Health Science Center at Houston (UT Health)	Houston	Texas	United States	77030
45	Mays Cancer Center	San Antonio	Texas	United States	78229
46	University of Utah	Salt Lake City	Utah	United States	84112
47	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109--1023
48	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
49	British Columbia Cancer Agency - Abbotsford	Abbotsford	British Columbia	Canada	V2S OC2
50	British Columbia Cancer Agency - Victoria	Victoria	British Columbia	Canada	V8R 6V5
51	The Ottawa Hospital - General Campus	Ottawa	Ontario	Canada	K1H 8L6
52	Hôpital Fleurimont	Sherbrooke	Quebec	Canada	J1H 5N4
53	Saskatoon Cancer Center	Saskatoon	Saskatchewan	Canada	S7N 4H4
54	First Affiliated Hospital of USTC - Anhui Provincial Hospital	Hefei	Anhui	China	230071
55	Beijing Tian Tan Hospital, Capital Medical University	Beijing	Beijing	China	100070
56	Sanbo Brain Hospital, Capital Medical University	Beijing	Beijing	China	100093
57	Peking Union Medical College Hospital	Beijing	Beijing	China	100730
58	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong	China	510060
59	Shenzhen Second People's Hospital	Shenzhen	Guangdong	China	518035
60	Tongji Hospital	Wuhan	Hubei	China	430030
61	Shengjing Hospital - Nanhu Campus	Shenyang	Liaoning	China	110004
62	Tangdu Hospital	Xian	Shaanxi	China	710038
63	Huashan Hospital Affiliated to Fudan University	Shanghai	Shanghai	China	200040
64	Tianjin Huanhu Hospital	Jinnan	Tianjin	China	300350
65	General Hospital of Tianjin Medical University	Tianjin	Tianjin	China	300052

Sponsors and Collaborators

• Denovo Biopharma LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Denovo Biopharma LLC
• ClinicalTrials.gov Identifier: NCT03776071
• Other Study ID Numbers: DB102-01
• First Posted: Dec 14, 2018
• Last Update Posted: Jun 14, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Glioblastoma; Temozolomide

Study Results

No Results Posted as of Jun 14, 2022