A Study of DSP-7888 Dosing Emulsion in Combination With Bevacizumab in Patients With Recurrent or Progressive Glioblastoma Following Initial Therapy

Sponsor

Sumitomo Pharma Oncology, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03149003

Collaborator

(none)

236

Enrollment

Locations

Arms

70.8

Anticipated Duration (Months)

3.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an event driven, adaptive design, a randomized, active-controlled, multicenter, open-label, parallel groups, Phase 3 study of DSP-7888 Dosing Emulsion plus Bevacizumab versus Bevacizumab alone in patients with recurrent or progressive glioblastoma multiforme (GBM) following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma	Drug: DSP-7888 Dosing Emulsion Drug: Bevacizumab	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

236 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Multicenter, Adaptive Phase 3 Study of DSP-7888 Dosing Emulsion in Combination With Bevacizumab Versus Bevacizumab Alone in Patients With Recurrent or Progressive Glioblastoma Following Initial Therapy (WIZARD 201G)

Actual Study Start Date :

Dec 8, 2017

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: DSP-7888 Dosing Emulsion plus Bevacizumab	Drug: DSP-7888 Dosing Emulsion DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above. Other Names: adegramotide and nelatimotide Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Names: Avastin
Active Comparator: Arm 2: Bevacizumab	Drug: Bevacizumab Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg. Other Names: Avastin

Arm

Intervention/Treatment

Experimental: Arm 1: DSP-7888 Dosing Emulsion plus Bevacizumab

Drug: DSP-7888 Dosing Emulsion

DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above.

Other Names:

adegramotide and nelatimotide

Drug: Bevacizumab

Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.

Other Names:

Avastin

Active Comparator: Arm 2: Bevacizumab

Drug: Bevacizumab

Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.

Other Names:

Avastin

Outcome Measures

Primary Outcome Measures

Determination of the safety and tolerability of DSP-7888 Dosing Emulsion by assessing dose-limiting toxicities (DLTs) [4 weeks]
Part 1
Overall Survival [24 months]
Part 2: To assess the effect of DSP-7888 Dosing Emulsion plus Bevacizumab versus Bevacizumab alone on the Overall Survival of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy. Overall survival is defined as the interval between randomization and death from any cause.

Secondary Outcome Measures

Twelve-month Survival [12 months]
Part 2: To assess the effect of DSP-7888 Dosing Emulsion plus Bevacizumab versus Bevacizumab alone on the survival rate at 12 months after randomization of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy.
Progression Free Survival [24 months]
Part 2: To assess the effect of DSP-7888 Dosing Emulsion plus Bevacizumab versus Bevacizumab alone on the Progression Free Survival (PFS) of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy. Progression-free survival is defined as the interval between randomization and progression or death from any cause any cause as determined by the central radiology body.
Six-month Progression Free Survival [6 months]
Part 2: To assess the effect of DSP-7888 Dosing Emulsion plus Bevacizumab versus Bevacizumab alone on the 6-months PFS of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy. Six-month PFS is defined as the proportion of patients alive at 6 months after randomization and without progressive neoplastic disease.
Response Rate [24 months]
Part 2: To assess the effect of DSP-7888 Dosing Emulsion plus Bevacizumab versus Bevacizumab alone on the response rate of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy. The response rate is defined as the proportion of patients exhibiting a response (complete response [CR] plus partial response [PR]) based on the Modified Response Assessment in Neuro-Oncology (RANO) criteria as determined by the central radiology body.
Duration of Response [24 months]
Part 2: To assess the effect of DSP-7888 Dosing Emulsion plus Bevacizumab versus Bevacizumab alone on the duration of response of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy. The duration of response is defined as the interval between first documented oncological response and progression of disease or death from any cause, with response based on the mRANO criteria as determined by the central radiology body.
Number of Patients with Adverse Events [24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients or their legal representatives must be able to provide written informed consent.
Histologically confirmed diagnosis of supratentorial GBM (Grade 4 astrocytoma).
Radiographic evidence of first recurrence or progression of GBM following primary therapy consisting of surgery (biopsy or resection) and chemoradiation; patients may have undergone a second debulking surgery following initial recurrence or progression. Patients whose tumors are O6 methyl guanyl-methyltransferase (MGMT) methylated-promoter negative need not have received chemotherapy in the past to be eligible.
Human leukocyte antigen type HLA-A02:01, HLA-A02:06, or HLA-A*24:02.
Age ≥18.
KPS score of ≥60.
Serum creatinine value <2X the upper limit of normal (ULN) for the reference laboratory.
Alanine aminotransferase/aspartate aminotransferase <3X the ULN and total bilirubin <2× the ULN for the reference laboratory.
Men and women of childbearing potential must agree to use a reliable method of contraception (oral contraceptives, implantable hormonal contraceptives, or double barrier method) or agree to completely refrain from heterosexual intercourse for the duration of the study and for 180 days following the last dose of DSP-7888 Dosing Emulsion.
Patients must have recovered from the effect of all prior therapy to Grade 2 or less.
Patients must be at least 28 days from any major surgery, and any surgery incisions or wounds must be completely healed.
Patients must be at least 12 weeks from the completion of prior radiation therapy (RT) in order to discriminate pseudo progression of disease from progression.
Patients must be at least 4 weeks from the completion of prior systemic or intracranial chemotherapy.
Patients must stop Novo-TTF treatment one day prior to study therapy (no washout period is needed). However, any wounds from TTF must be adequately healed per Inclusion Criterion #11.15. For patients who are not receiving therapeutic anticoagulation treatment, an international normalized ratio (INR) and a PTT ≤ 1.5 × the ULN; patients who are receiving anticoagulation treatment should be on a stable dose.
Patient's left ventricular ejection fraction (LVEF) > 40%. 17. Patient has a resting pulse oximetry of 90% or higher.

Exclusion Criteria:

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

Prior therapy with Bev.
Patients with secondary GBM.
Any anti-neoplastic therapy, including RT, for first relapse or recurrence.
Evidence of leptomeningeal spread of tumor or any history, presence, or suspicion of metastatic disease extracranially.
Evidence of impending herniation on imaging.
Has known multifocal disease. Multifocal disease is defined as discrete sites of disease without contiguous T2/FLAIR abnormality that require distinct radiotherapy ports. Satellite lesions that are associated with a contiguous area of T2/FLAIR abnormality as the main lesion(s) and that are encompassed within the same radiotherapy port as the main lesion(s) are permitted.
Patients with infections that have required treatment with systemic antibiotics within 7 days of first dose of protocol therapy.
The need for systemic glucocorticoids in doses in excess of 4 mg/day of dexamethasone or in comparable doses with other glucocorticoids.
Treatment with any investigational agents within 5 half-lives of the agent in question or, if the half-life is unknown, within 28 days of enrollment.
Pregnant or lactating females.
Prior history of malignancy within 3 years of enrollment other than basal or squamous cell carcinoma of the skin, cervical intra-epithelial neoplasia, in situ carcinoma of the breast, or prostate cancer treated with surgery or RT with a prostate specific antigen of <0.01 ng/mL.
Patients with active autoimmune diseases within 2 years of enrollment into the study including, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, Wegener's granulomatosis, ulcerative colitis, Crohn's disease, myasthenia gravis, Graves' disease, or uveitis except for psoriasis not requiring systemic therapy, vitiligo or alopecia areata, or hypothyroidism; if an autoimmune condition has been clinically silent for 12 months or greater, the patient may be eligible for enrollment.
Patients on immunosuppressive therapies; the use of topical, inhalational, ophthalmologic or intra articular glucocorticoids, or the use of physiologic replacement doses of glucocorticoids are permitted.
Patients with primary immunodeficiency diseases.
Patients with significant bleeding in the preceding 6 months or with known coagulopathies.
History of abdominal fistula, intestinal perforation, or intra-abdominal abscess in the preceding 12 months.
Positive serology for human immunodeficiency virus (HIV) infection, active hepatitis B*, or untreated hepatitis C; patients who have completed a course of anti-viral treatment for hepatitis C are eligible.

o *In cases of negative results for HepB surface antigen with positive HepB core antibody, HBV DNA testing is required.

Patient has a medical history of frequent ventricular ectopy, e.g., non-sustained ventricular tachycardia (VT).
Significant cardiovascular disease, including New York Hospital Association Class III or IV congestive heart failure, myocardial infarction within 6 months of enrollment, unstable angina, poorly controlled cardiac arrhythmias, or stroke within the preceding 6 months.
Any other uncontrolled inter current medical condition, including systemic fungal, bacterial, or viral infection; uncontrolled hypertension; diabetes mellitus; or chronic obstructive pulmonary disease requiring 2 or more hospitalizations in the preceding 12 months.
Any psychiatric condition, substance abuse disorder, or social situation that would interfere with a patient's cooperation with the requirements of the study.
Known sensitivity to Bev or any of the components of DSP-7888 Dosing Emulsion.
Patient has a QTcF (QT corrected based on Fridericia's equation) interval > 480 msec (CTCAE = Grade 2) or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening. (Patients with bundle branch block and a prolonged QTc interval should be reviewed by the Medical Monitor for potential inclusion.)
Patient has dyspnea at rest (CTCAE ≥ Grade 3) or has required supplemental oxygen within 2 weeks of study enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Center for Neurosciences	Tucson	Arizona	United States	85718
3	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
4	UCSD- Moores Cancer Center	La Jolla	California	United States	92093
5	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
6	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
7	Neuro-Oncology/ US Irvine Medical Center	Orange	California	United States	92868
8	Sansum Clinic	Santa Barbara	California	United States	93105
9	John Wayne Cancer Institute	Santa Monica	California	United States	90404
10	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
11	Piedmont brain tumor center	Atlanta	Georgia	United States	30309
12	Rush University Medical Center	Chicago	Illinois	United States	60612
13	University of Kentucky / Department of Internal Medicine / Markey Cancer Center	Lexington	Kentucky	United States	40536
14	Norton Cancer Institute	Louisville	Kentucky	United States	40202
15	Tufts Medical Center	Boston	Massachusetts	United States	02111
16	Henry Ford Health System	Detroit	Michigan	United States	48202
17	Abbott Northwestern Hospital	Minneapolis	Minnesota	United States	55407
18	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
19	Dent Neurosciences Research Center	Amherst	New York	United States	14226
20	Weill Cornell Medicine	New York	New York	United States	10021
21	Columbia University Medical Center/ Neurological Institute of NY	New York	New York	United States	10032
22	University of Rochester Medical Center	Rochester	New York	United States	14642
23	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
24	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
25	University of Toledo	Toledo	Ohio	United States	43606
26	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
27	University of Pittsburgh Medical Center (UPMC)	Pittsburgh	Pennsylvania	United States	15232
28	Rhode Island Hospital	Providence	Rhode Island	United States	02903
29	University OF Tennessee Academic Medical Center Cancer Institute	Knoxville	Tennessee	United States	37920
30	Texas Oncology Austin Midtown	Austin	Texas	United States	78705
31	Baylor Scott and White	Dallas	Texas	United States	75246
32	Houston Methodist	Houston	Texas	United States	77030
33	Mischer Neuroscience Associates/Memorial Hermann Hospital	Houston	Texas	United States	77030
34	Renovatio Clinical	The Woodlands	Texas	United States	77380
35	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
36	Swedish Medical Center	Seattle	Washington	United States	98122
37	University of Wisconsin Hospital	Madison	Wisconsin	United States	53792
38	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
39	Montreal Neurological Institute and Hospital	Montreal	Quebec	Canada	H3A 2B4
40	University of Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5N4
41	Hokkaido University Hospital	Sapporo	Hokkaido	Japan	060-8648
42	Kagoshima University Hospital	Kagoshima-shi	Kagoshima	Japan	890-8520
43	Niigata University Medical and Dental Hospital	Chuo Ku	Niigata	Japan	951-8520
44	Osaka International Cancer Institute	Otemae Chuo-ku	Osaka	Japan	541-8567
45	The University of Tokyo Hospital	Bunkyo-ku	Tokyo	Japan	113-8655
46	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	104-0045
47	Hiroshima University Hospital	Hiroshima		Japan	734-8551
48	Kumamoto University Hospital	Kumamoto		Japan	860-8556
49	University Hospital, Kyoto Prefectural University of Medicine	Kyoto		Japan	602-8566
50	National Hospital Organization Kyoto Medical Center	Kyoto		Japan	612-8555
51	Tokyo Women's Medical University Hospital	Shinjuku-Ku		Japan	162-8666
52	Yamagata University Hospital	Yamagata		Japan	990-9585
53	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
54	Gangnam Severance Hospital	Gangnam-gu	Seoul	Korea, Republic of	06273
55	Samsung Medical Center	Gangnam-gu	Seoul	Korea, Republic of	06351
56	Seoul National University Hospital	Jongno-gu	Seoul	Korea, Republic of	03080
57	The Catholic University of Korea, Seoul St. Mary's Hospital	Seocho-gu	Seoul	Korea, Republic of	06591
58	Severance Hospital	Seodaemun-gu	Seoul	Korea, Republic of	03722
59	China Medical University Hospital	Yude Road	Taichung	Taiwan	40447
60	National Taiwan University Hospital	Chung-Shan South Road	Taipei	Taiwan	100
61	Chang Gung Memorial Hospital	Taoyuan City		Taiwan