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

• ClinicalTrials.gov Identifier: NCT05023551
• Recruitment Status: Active, not recruiting
• First Posted: August 26, 2021
• Last Update Posted: March 29, 2024
• Sponsor: Sumitomo Pharma America, Inc.
• Information provided by (Responsible Party): Sumitomo Pharma America, Inc.

Tracking Information

• First Submitted Date: July 27, 2021
• First Posted Date: August 26, 2021
• Last Update Posted Date: March 29, 2024
• Actual Study Start Date: September 8, 2021
• Actual Primary Completion Date: October 10, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 20, 2021)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 11, 2022)

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

Original Secondary Outcome Measures (submitted: August 20, 2021)

• Dose Escalation: Characterize the PK profile for AUC [ Time Frame: 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 ]
  PK assessed for AUC
• Dose Escalation: Characterize the PK profile for Cmax [ Time Frame: 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 ]
  PK assessed for Cmax
• Dose Escalation: Characterize the PK profile for tmax [ Time Frame: 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 ]
  PK assessed for tmax
• Dose Escalation: Characterize the PK profile for t1/2 [ Time Frame: 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] ]
  PK assessed for t1/2
• Dose Escalation: Characterize the PK profile for Racc [ Time Frame: Cycle 1 Day 8, 15 and 22 and Cycle 2 Day 1, each cycle is 28 days ]
  PK assessed for Racc

Current Other Pre-specified Outcome Measures (submitted: August 20, 2021)

Exploratory: Assess the PD effect of DSP-0390 [ Time Frame: From first date of treatment, blood tests performed at 8 week intervals through study completion, an average of 6 months ]

Biomarker (lathosterol/zymostenol ratio) in blood

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Study of DSP-0390 in Patients With Recurrent High-Grade Glioma
• Official Title: A Phase 1 Study of DSP-0390 in Patients With Recurrent High-Grade Glioma
• Brief Summary: This is a study of DSP-0390 in patients with recurrent high grade glioma.
• Detailed Description: This study will evaluate the safety and efficacy of DSP-0390 in patients with recurrent high grade glioma.
• Study Type: Interventional
• Study Phase: Early Phase 1

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

This is a Phase 1 dose-escalation study with a Part 2 expansion to evaluate the safety, PK, PD, and preliminary antitumor activity of orally administered DSP 0390 in patients with recurrent high-grade glioma. Patients in this study will receive DSP-0390 orally once daily. The study will be divided into 28-day cycles for safety and response assessments. Patients will continue treatment until progression of disease, unacceptable toxicity, withdrawal of consent, loss to follow-up, or discontinuation of the patient by the investigator.

Dose-escalation will evaluate increasing dose levels of DSP-0390 to determine the MTD and/or a suitable lower dose for expansion (the RDE) in patients with recurrent WHO Grade III or IV malignant glioma. Once the MTD and/or RDE has been established, the dose escalation (Part 2) will evaluate preliminary clinical activity and the safety and tolerability of DSP-0390 in patients with recurrent WHO Grade 4 glioblastoma multiforme (GBM).

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• High Grade Glioma
• Glioblastoma Multiforme

Intervention

Drug: DSP-0390

DSP-0390 administered orally

Study Arms

Experimental: Single arm DSP-0390

Arm Description [*] DSP-0390 by oral administration

Intervention: Drug: DSP-0390

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: March 27, 2024): 39
• Original Estimated Enrollment (submitted: August 20, 2021): 70
• Estimated Study Completion Date: July 31, 2024
• Actual Primary Completion Date: October 10, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan, United States

Administrative Information

• NCT Number: NCT05023551
• Other Study ID Numbers: DSP-0390-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sumitomo Pharma America, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Sumitomo Pharma America, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Sumitomo Pharma America, Inc.
• Verification Date: March 2024