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

NCT ID: NCT03149003

Last Updated: 2023-11-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 221 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-08
• Study Completion Date: 2021-08-30

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.

Conditions

Glioblastoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: DSP-7888 Dosing Emulsion plus Bevacizumab

Group Type: EXPERIMENTAL

DSP-7888 Dosing Emulsion

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Arm 2: Bevacizumab

Group Type: ACTIVE_COMPARATOR

Bevacizumab

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Bevacizumab

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

Intervention Type: DRUG

Other Intervention Names

adegramotide and nelatimotide; Avastin

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sumitomo Pharma America, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Center for Neurosciences

Tucson, Arizona, United States

Highlands Oncology Group

Fayetteville, Arkansas, United States

UCSD- Moores Cancer Center

La Jolla, California, United States

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Neuro-Oncology/ US Irvine Medical Center

Orange, California, United States

Sansum Clinic

Santa Barbara, California, United States

John Wayne Cancer Institute

Santa Monica, California, United States

Rocky Mountain Cancer Center

Denver, Colorado, United States

Piedmont brain tumor center

Atlanta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Kentucky / Department of Internal Medicine / Markey Cancer Center

Lexington, Kentucky, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Tufts Medical Center

Boston, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

Abbott Northwestern Hospital

Minneapolis, Minnesota, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Dent Neurosciences Research Center

Amherst, New York, United States

Weill Cornell Medicine

New York, New York, United States

Columbia University Medical Center/ Neurological Institute of NY

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

University Hospitals of Cleveland

Cleveland, Ohio, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

University of Toledo

Toledo, Ohio, 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 Tennessee Academic Medical Center Cancer Institute

Knoxville, Tennessee, United States

Texas Oncology Austin Midtown

Austin, Texas, United States

Baylor Scott and White

Dallas, Texas, United States

Houston Methodist

Houston, Texas, United States

Mischer Neuroscience Associates/Memorial Hermann Hospital

Houston, Texas, United States

Renovatio Clinical

The Woodlands, Texas, United States

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Swedish Medical Center

Seattle, Washington, United States

University of Wisconsin Hospital

Madison, Wisconsin, United States

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Montreal Neurological Institute and Hospital

Montreal, Quebec, Canada

University of Sherbrooke

Sherbrooke, Quebec, Canada

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Kagoshima University Hospital

Kagoshima, Kagoshima-ken, Japan

Niigata University Medical and Dental Hospital

Chuo Ku, Niigata, Japan

Osaka International Cancer Institute

Chuo Ku, Osaka, Japan

The University of Tokyo Hospital

Bunkyo-ku, Tokyo, Japan

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Hiroshima University Hospital

Hiroshima, , Japan

Kumamoto University Hospital

Kumamoto, , Japan

University Hospital, Kyoto Prefectural University of Medicine

Kyoto, , Japan

National Hospital Organization Kyoto Medical Center

Kyoto, , Japan

Tokyo Women's Medical University Hospital

Shinjuku-Ku, , Japan

Yamagata University Hospital

Yamagata, , Japan

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital

Seoul, , South Korea

Gangnam Severance Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

China Medical University Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital

Taoyuan, , Taiwan

Countries

United States; Canada; Japan; South Korea; Taiwan

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

BBI-DSP7888-201G

Identifier Type: -

Identifier Source: org_study_id