Study of DSP-0390 in Patients With Recurrent High-Grade Glioma

A Phase 1 Study of DSP-0390 in Patients With Recurrent High-Grade Glioma

This is a study of DSP-0390 in patients with recurrent high grade glioma.

Study Overview

• Status: Active, not recruiting
• Conditions: Glioblastoma Multiforme; High Grade Glioma
• Intervention / Treatment: Drug: DSP-0390

Detailed Description

This study will evaluate the safety and efficacy of DSP-0390 in patients with recurrent high grade glioma.

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Japan
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Sakyo-ku
    • Kyoto, Sakyo-ku, Japan, 606-8507
      • Kyoto University Hospital
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California at San Francisco
  • Massachusetts
    • Boston, Massachusetts, United States, 10032
      • Dana Farber Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute, University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Estimated life expectancy >+3 months Recovery from toxic effects of prior therapy to NCI CTCAE v5.0 Grade 1 (non-hematologic toxicities) or Grade <=2(hematologic toxicities, except deep vein thrombosis) KPS >=70%

Adequate organ function as determined by:

• Absolute Neutrophil ≥1500/microliter (may not use G-CSF or GM CSF)
• Platelet ≥100 × 103/microliter
• Hemoglobin ≥9 g/dL (may not transfuse or use erythropoietin to obtain this Hgb level)
• Creatinine Clearance ≥ 40ml/min (Cockcroft-Gault)
• Total bilirubin ≤1.5 times ULN (or ≤ 2 times ULN for patients with known Gilbert's syndrome)
• AST ≤ 3 times ULN
• ALT ≤ 3 times ULN
• INR, PT, PTT, or aPTT ≤1.5 x ULN Note: The use of anticoagulants is permitted as long as the PT/(a)PTT is within therapeutic limits (according to the local institution standard) and the patient has been on a stable anticoagulant regimen for at least 2 weeks prior to study Day 1.

If on antiepileptic drug; dose must be stable and no seizures 14 days prior to study Day 1 If on corticosteroids at baseline, dose must be stable or decreasing for at least 5 days prior to study Day 1. For the dose expansion part of the study, the dose must be ≤ 4 mg dexamethasone per day (or equivalent dose if other corticosteroids are used). A higher stable dose of corticosteroids, if used as HRT, may be allowed upon discussion with the Medical Monitor.

Females of childbearing potential must have a negative serum or urine pregnancy test Male or female patients of child-producing potential must agree to use contraception or use prevention of pregnancy measures or agreement to refrain completely from heterosexual intercourse during the study and for 6 months (females & males) after the last dose of study drug

Exclusion Criteria:

Prior therapy with bevacizumab or other anti-vascular endothelial growth factor (VEGF) treatments within 3 months prior to study Day 1, Multifocal disease, leptomeningeal metastasis, or extracranial metastasis Abnormal ECGs that are clinically significant, including those where QT prolongation (QTcF>450 msec for males and >470 msec for females); and/or history of Torsade de Pointes Left ventricular ejection fraction <40% as determined by ECHO or MUGA Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally Know active Crohn's or other inflammatory bowel disease History of another primary cancer within the 2 years prior to study Day 1, except for the following: non-melamona skin cancer, cervical carcinoma in situ, superficial bladder cancer that has been removed or curatively treated.

Have a known detectable viral load for HIV or HVC, or evidence of a HBV surface antigen, all being indicative of active infection. [Note: Female breastfeeding patients may be enrolled if they interrupt breastfeeding. Breastfeeding should not be resumed for at least 6 months after the last dose of study drug.]

The presence of any active retinal abnormality determined by screening tests using visual acuity, visual field, fundoscopy, and OCT

Significant cardiovascular disease, including NYHA Class III or IV congestive heart failure, myocardial infarction, unstable angina, poorly controlled cardiac arrhythmias, or stroke in the preceding 6 months prior to study Day 1

Uncontrolled intercurrent illness including, but not limited to, psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state

Major surgical procedure, surgical resection, open biopsy, or significant traumatic injury within 4 weeks prior to study Day 1 or anticipation of need for major surgical procedure during the course of the study

Minor surgical procedures, fine needle aspirations, or core biopsies within 7 days prior to study Day 1

Evidence of CNS hemorrhage on baseline MRI or CT scan (except for postsurgical, asymptomatic, Gr 1 hemorrhage that has been stable at least 4 weeks for enrolled patients) Chemotherapy or investigational anticancer therapy administered within 4 weeks (except 6 weeks for nitrosoureas and immunotherapy, or 8 weeks for an implanted nitrosoureas wafer) prior to study Day 1

Radiotherapy within 12 weeks prior to study Day 1, unless relapse is confirmed by tumor biopsy or new lesion outside of radiation field, or if there are 2 MRIs (performed 8 weeks apart) confirming progressive disease

Concurrent use of prohibited medications: carbamazepine, phenytoin, phenobarbital, and other strong or moderate CYP3A4 inhibitors or inducers, and strong CYP2D6 inhibitors. These should be discontinued 1 week or 5 half-lives (whichever is greater) prior to study Day 1

Concurrent treatment with Tumor Treatment Field (Optune) is not allowed. Patients must stop Optune 1 day prior to the first dose of study drug. Any wounds from Optune must be healed adequately prior to study Day 1

History of, within 6 months of study Day 1:

1. Pneumonitis or interstitial lung disease
2. Any other lung condition that in the investigators' judgement may put the patient at an increased risk for lung toxicity (including, but not limited to, suspected interstitial lung disease or radiation-induced lung injury)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm DSP-0390; Arm Description [*] DSP-0390 by oral administration	Drug: DSP-0390; DSP-0390 administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation: Assess safety of DSP-0390 by Incidence of TEAEs and SAEs in adult patients with recurrent high-grade glioma	Occurrence of DLTs by Incidence of TEAEs and SAEs, as assessed by NCI CTCAE v5.0	From date of treatment through 30 days after End of Treatment an average of 6 months
Dose Escalation: Assess safety of DSP-0390 by severity of TEAEs and SAEs in adult patients with recurrent high-grade glioma	Occurrence of DLTs by severity of TEAEs and SAEs, as assessed by NCI CTCAE v5.0	From date of treatment through 30 days after End of Treatment an average of 6 months
Dose Escalation: Determine the MTD and/or RDE of DSP-0390	Incidence of dose-limiting toxicities	From date of first treatment through Cycle 1 (28-day cycle) DLT monitoring period
Dose Expansion: Evaluate the change in Baseline tumor activity of DSP-0390 using radiologic assessments.	Evaluate the change in baseline tumor activity of DSP-0390 using radiologic assessments evaluated by RANO 2010 Evaluation Criteria	From date of first treatment, assessed by radiologic examination performed at 8-week intervals through study completion, an average of 6 months
Dose Expansion: Evaluate the safety of the Recommended Phase 2 Dose of DSP-0390 by assessment of incidence of TEAEs and SAEs	Assess the safety of the Recommended Phase 2 Dose of DSP-0390 by assessment of incidence of TEAEs and SAEs	From date of first treatment through study completion, an average of 6 months
Dose Expansion: Evaluate the safety of the Recommended Phase 2 Dose by assessment of severity of TEAEs and SAEs	Assess the safety of the Recommended Phase 2 Dose of DSP-0390 by assessment of severity of TEAEs and SAEs	From date of first treatment through study completion, an average of 6 months
Assess safety of DSP-0390 by Incidence of SAEs in adult patients with recurrent high-grade glioma consented under Protocol Amendment 5	Incidence of SAEs, as assessed by NCI CTCAE v5.0	From date of treatment through 30 days after End of Treatment an average of 12 months
Assess safety of DSP-0390 by Incidence of AEs resulting in study discontinuation in adult patients with recurrent high-grade glioma consented under Protocol Amendment 5	Incidence of AEs resulting in study discontinuation, as assessed by NCI CTCAE v5.0	From date of treatment through 30 days after End of Treatment an average of 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation: Characterize the PK profile for AUC	PK assessed for AUC	Cycle 1 Day 1 and Cycle 2 Day 1- 0, 30 min, and 1, 2, 4, 6, 8, 10, 12 hrs, each cycle is 28 days
Dose Escalation: Characterize the PK profile for Cmax	PK assessed for Cmax	Cycle 1 Day 1 and Cycle 2 Day 1 -0, 30 min, and 1, 2, 4, 6, 8, 10, 12 hrs , each cycle is 28 days
Dose Escalation: Characterize the PK profile for tmax	PK assessed for tmax	Cycle 1 Day 1 and Cycle 2 Day 1- 0, 30 min, and 1, 2, 4, 6, 8, 10, 12 hrs , each cycle is 28 days
Dose Escalation: Characterize the PK profile for t1/2	PK assessed for t1/2	From date of first treatment, Cycle 1 Day 1 and Cycle 2 Day 1- 0, 30 min, and 1, 2, 4, 6, 8, 10, 12 hrs , each cycle is 28 days]
Dose Escalation: Characterize the PK profile for Racc	PK assessed for Racc	Cycle 1 Day 8, 15 and 22 and Cycle 2 Day 1, each cycle is 28 days
Dose Escalation: Evaluate preliminary antitumor activity	Objective response (complete or partial response) and duration of response assessed by RANO criteria.	From date of first treatment, assessed by radiologic examination performed at 8-week intervals through study completion, an average of 6 months]

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory: Assess the PD effect of DSP-0390	Biomarker (lathosterol/zymostenol ratio) in blood	From first date of treatment, blood tests performed at 8 week intervals through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: Sumitomo Pharma America, Inc.
• Investigators: Study Director: Jian Li, MD, Sumitomo Pharma America, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2021
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: July 27, 2021
• First Submitted That Met QC Criteria: August 20, 2021
• First Posted (Actual): August 26, 2021

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Brain Tumor; High grade glioma; Glioblastoma Multiforme (GMB); Emopamil binding protein; 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Central Nervous System Neoplasms; Glioblastoma; Glioma; Brain Neoplasms
• Other Study ID Numbers: DSP-0390-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No