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

Glioblastoma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03149003
• Other study ID #: BBI-DSP7888-201G
• Status: Completed
• Phase: Phase 3
• Start date: December 8, 2017
• Est. completion date: August 30, 2021

Study information

• Verified date: November 2023
• Source: Sumitomo Pharma America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: August 30, 2021
• Est. primary completion date: August 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-A*02:01, HLA-A*02:06, 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.

Related Conditions & MeSH terms

• Glioblastoma

Intervention

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

Locations

Country	Name	City	State
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	University of Sherbrooke	Sherbrooke	Quebec
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Japan	The University of Tokyo Hospital	Bunkyo-ku	Tokyo
Japan	Niigata University Medical and Dental Hospital	Chuo Ku	Niigata
Japan	Osaka International Cancer Institute	Chuo Ku	Osaka
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	Hiroshima University Hospital	Hiroshima
Japan	Kagoshima University Hospital	Kagoshima-shi	Kagoshima
Japan	Kumamoto University Hospital	Kumamoto
Japan	National Hospital Organization Kyoto Medical Center	Kyoto
Japan	University Hospital, Kyoto Prefectural University of Medicine	Kyoto
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Tokyo Women's Medical University Hospital	Shinjuku-Ku
Japan	Yamagata University Hospital	Yamagata
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital	Taoyuan City
United States	Dent Neurosciences Research Center	Amherst	New York
United States	Piedmont brain tumor center	Atlanta	Georgia
United States	Texas Oncology Austin Midtown	Austin	Texas
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Baylor Scott and White	Dallas	Texas
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Houston Methodist	Houston	Texas
United States	Mischer Neuroscience Associates/Memorial Hermann Hospital	Houston	Texas
United States	University of Tennessee Academic Medical Center Cancer Institute	Knoxville	Tennessee
United States	UCSD- Moores Cancer Center	La Jolla	California
United States	University of Kentucky / Department of Internal Medicine / Markey Cancer Center	Lexington	Kentucky
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Wisconsin Hospital	Madison	Wisconsin
United States	Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	Columbia University Medical Center/ Neurological Institute of NY	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	Neuro-Oncology/ US Irvine Medical Center	Orange	California
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center (UPMC)	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of Rochester Medical Center	Rochester	New York
United States	Sansum Clinic	Santa Barbara	California
United States	John Wayne Cancer Institute	Santa Monica	California
United States	Swedish Medical Center	Seattle	Washington
United States	Renovatio Clinical	The Woodlands	Texas
United States	University of Toledo	Toledo	Ohio
United States	Center for Neurosciences	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Sumitomo Pharma America, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Japan,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Experienced a Dose-limiting Toxicity	The number of participants with dose-limiting toxicity (DLT) who were enrolled into Part 1 - the safety set.	Dose-limiting toxicity will be evaluated and applied from Day 1 through Day 29
Primary	Overall Survival (OS) of Patients With Recurrent or Progressive Glioblastoma Multiforme (GBM) Treated With DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone	The effect of DSP-7888 Dosing Emulsion plus BEV versus BEV alone on the OS of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy.	4 weeks after the patient has been off study treatment, every 3 months thereafter until death, the study closes, up to 24 months.
Secondary	Overall Survival (OS) of Patients With Recurrent or Progressive Glioblastoma Multiforme (GBM) Treated With DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone at 12 Months	The effect of DSP-7888 dosing emulsion plus BEV versus BEV alone on the OS of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy.	12 months
Secondary	Progression Free Survival (PFS) of Patients With Recurrent or Progressive GBM	The effect of DSP-7888 dosing emulsion plus Bevacizumab (BEV) versus BEV 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. PFS is defined as the interval between randomization and progression or death from any cause any cause as determined by the central radiology body.	The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause, up to 24 months
Secondary	Progression Free Survival (PFS) Rate in Patients With Recurrent or Progressive GBM at 6 Months	The effect of DSP-7888 dosing emulsion plus Bevacizumab (BEV) versus BEV alone on the Progression Free Survival (PFS) rate in patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy. PFS is defined as the interval between randomization date and progression or death from any cause as determined by the central radiology body. The percentage of patients who achieved PFS at 6 months are summarized.	The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause at 6 months
Secondary	The Effect of DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone on the Response Rate of Patients With Recurrent or Progressive GBM	Assessment of the objective response rate (ORR) of DSP-7888 dosing emulsion plus BEV versus BEV alone in patients with recurrent or progressive GBM. The response rate is defined as the percentage 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.	From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months
Secondary	Duration of Response in Patients With Recurrent or Progressive GBM Treated With DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone	The effect of DSP-7888 dosing emulsion plus BEV versus BEV alone on the duration of response of patients with recurrent or progressive GBM. The duration of response is defined as the interval between first documented oncological response and progression of disease or death from any cause.	From the date of first treatment up to 24 months
Secondary	Number of Participants With Adverse Events and Serious Adverse Events	Assessment of safety of DSP7888 dosing emulsion plus Bevacizumab (BEV) versus BEV alone in patients with recurrent or progressive GBM	The time from the date of first treatment, while the patient is on treatment, and for 30 days after stopping therapy, an average of 4 months