Clinical trial NCT03149003: A Study of DSP-7888 Dosing Emulsion in Combination With Bevacizumab in Patients With Recurrent or Progressive Glioblastoma Following Initial Therapy
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Glioblastoma
Keywords: Glioblastoma (GBM)
Wilms Tumor 1 (WT1)
Cancer Vaccines
Neoplasms
Astrocytoma
Glioma
Brain Cancer
Brain Tumor
Bevacizumab
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2017-05-11
Enrollment: 221
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Experienced a Dose-limiting Toxicity
timeFrame: Dose-limiting toxicity will be evaluated and applied from Day 1 through Day 29
measure: Overall Survival (OS) of Patients With Recurrent or Progressive Glioblastoma Multiforme (GBM) Treated With DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone
timeFrame: 4 weeks after the patient has been off study treatment, every 3 months thereafter until death, the study closes, up to 24 months.
Secondary outcomes:
measure: 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
timeFrame: 12 months
measure: Progression Free Survival (PFS) of Patients With Recurrent or Progressive GBM
timeFrame: 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
measure: Progression Free Survival (PFS) Rate in Patients With Recurrent or Progressive GBM at 6 Months
timeFrame: 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
measure: The Effect of DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone on the Response Rate of Patients With Recurrent or Progressive GBM
timeFrame: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months
measure: Duration of Response in Patients With Recurrent or Progressive GBM Treated With DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone
timeFrame: From the date of first treatment up to 24 months
measure: Number of Participants With Adverse Events and Serious Adverse Events
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Center for Neurosciences
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: La Jolla
country: United States
facility: UCSD- Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Orange
country: United States
facility: Neuro-Oncology/ US Irvine Medical Center
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Atlanta
country: United States
facility: Piedmont brain tumor center
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky / Department of Internal Medicine / Markey Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Amherst
country: United States
facility: Dent Neurosciences Research Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/ Neurological Institute of NY
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Knoxville
country: United States
facility: University of Tennessee Academic Medical Center Cancer Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Baylor Scott and White
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Houston
country: United States
facility: Mischer Neuroscience Associates/Memorial Hermann Hospital
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital
state: Wisconsin
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Sherbrooke
country: Canada
facility: University of Sherbrooke
state: Quebec
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kagoshima-shi
country: Japan
facility: Kagoshima University Hospital
state: Kagoshima
city: Chuo Ku
country: Japan
facility: Niigata University Medical and Dental Hospital
state: Niigata
city: Chuo Ku
country: Japan
facility: Osaka International Cancer Institute
state: Osaka
city: Bunkyo-ku
country: Japan
facility: The University of Tokyo Hospital
state: Tokyo
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kyoto
country: Japan
facility: University Hospital, Kyoto Prefectural University of Medicine
city: Kyoto
country: Japan
facility: National Hospital Organization Kyoto Medical Center
city: Shinjuku-Ku
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
References: