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

NCT03149003 | Completed Phase 3 Results FDA Drug

• 1 other identifier: BBI-DSP7888-201G
• Study Type: interventional
• Target: 221
• Locations: 5 countries
• Sites: 61

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

Keywords

Glioblastoma (GBM); Wilms Tumor 1 (WT1); Cancer Vaccines; Neoplasms; Astrocytoma; Glioma; Brain Cancer; Brain Tumor; Bevacizumab

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (6)

• 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

  12 months

• Progression Free Survival (PFS) of Patients With Recurrent or Progressive GBM

  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

• Progression Free Survival (PFS) Rate in Patients With Recurrent or Progressive GBM at 6 Months

  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

• The Effect of DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone on the Response Rate of Patients With Recurrent or Progressive GBM

  From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months

• Duration of Response in Patients With Recurrent or Progressive GBM Treated With DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone

  From the date of first treatment up to 24 months

Study Arms (2)

Arm 1: DSP-7888 Dosing Emulsion plus Bevacizumab

EXPERIMENTAL

Drug: DSP-7888 Dosing Emulsion; Drug: Bevacizumab

Arm 2: Bevacizumab

ACTIVE COMPARATOR

Drug: Bevacizumab

Interventions

DSP-7888 Dosing Emulsion 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.

Also known as: adegramotide and nelatimotide

Arm 1: DSP-7888 Dosing Emulsion plus Bevacizumab

Bevacizumab DRUG

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

Also known as: Avastin

Arm 1: DSP-7888 Dosing Emulsion plus Bevacizumab; Arm 2: Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patient's left ventricular ejection fraction (LVEF) \> 40%. 17. Patient has a resting pulse oximetry of 90% or higher.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (61)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Center for Neurosciences

Tucson, Arizona, 85718, United States

Location

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

UCSD- Moores Cancer Center

La Jolla, California, 92093, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Neuro-Oncology/ US Irvine Medical Center

Orange, California, 92868, United States

Location

Sansum Clinic

Santa Barbara, California, 93105, United States

Location

John Wayne Cancer Institute

Santa Monica, California, 90404, United States

Location

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

Piedmont brain tumor center

Atlanta, Georgia, 30309, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

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

Lexington, Kentucky, 40536, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Abbott Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Dent Neurosciences Research Center

Amherst, New York, 14226, United States

Location

Weill Cornell Medicine

New York, New York, 10021, United States

Location

Columbia University Medical Center/ Neurological Institute of NY

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

University of Toledo

Toledo, Ohio, 43606, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15232, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

University of Tennessee Academic Medical Center Cancer Institute

Knoxville, Tennessee, 37920, United States

Location

Texas Oncology Austin Midtown

Austin, Texas, 78705, United States

Location

Baylor Scott and White

Dallas, Texas, 75246, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

Mischer Neuroscience Associates/Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

Renovatio Clinical

The Woodlands, Texas, 77380, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

University of Wisconsin Hospital

Madison, Wisconsin, 53792, United States

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

University of Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Kagoshima University Hospital

Kagoshima, Kagoshima-ken, 890-8520, Japan

Location

Niigata University Medical and Dental Hospital

Chuo Ku, Niigata, 951-8520, Japan

Location

Osaka International Cancer Institute

Chuo Ku, Osaka, 541-8567, Japan

Location

The University of Tokyo Hospital

Bunkyo-ku, Tokyo, 113-8655, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Hiroshima University Hospital

Hiroshima, 734-8551, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

University Hospital, Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

Location

National Hospital Organization Kyoto Medical Center

Kyoto, 612-8555, Japan

Location

Tokyo Women's Medical University Hospital

Shinjuku-Ku, 162-8666, Japan

Location

Yamagata University Hospital

Yamagata, 990-9585, Japan

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Gangnam Severance Hospital

Seoul, 06273, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

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

Seoul, 06591, South Korea

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Chang Gung Memorial Hospital

Taoyuan, Taiwan

Location

MeSH Terms

Conditions

Glioblastoma; Wilms Tumor; Neoplasms; Astrocytoma; Glioma; Brain Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Sheila Dhaskali
• Organization: Sumitomo Pharma Oncology

Sheila.dhaskali@oncology.sumitomo-pharma.com

617-674-6800

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: May 11, 2017
• Study Start: December 8, 2017
• Primary Completion: August 30, 2021
• Study Completion: August 30, 2021
• Last Updated: November 15, 2023
• Results First Posted: January 30, 2023

Record last verified: 2023-11

Locations

TW (3); KR (6); CA (3); US (37); JP (12)