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

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 70

Inclusion Criteria

1.Estimated life expectancy >= 3 months
2.Recovery from toxic effects of prior therapy to NCI CTCAE v5.0 Grade 1 (nonhematologic toxicities) or Grade <=2(hematologic toxicities, except deep vein thrombosis)
3.Karnofsky Performance Status (KPS) score >= 70%
4.Adequate organ function as determined by:
a. Absolute Neutrophil >=1500/microliter (may not use G-CSF or GM CSF)
b. Platelet >=100 * 10^3/microliter
c. Hemoglobin >=9 g/dL (may not transfuse or use erythropoietin to obtain this Hgb level)
d. Creatinine Clearance >= 40ml/min (Cockcroft-Gault)
e. Total bilirubin <=1.5 times ULN (or <= 2 times ULN for patients with known Gilbert syndrome)
f. AST <= 3 times ULN
g. ALT <= 3 times ULN
h. 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 the first study Day 1
5.If on antiepileptic drug; dose must be stable and no seizures 14 days prior to study Day 1
6.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.
7.Females of childbearing potential must have a negative serum or urine pregnancy test
8.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

1.Prior therapy with bevacizumab or other anti-vascular endothelial growth factor (-VEGF) treatments within 3 months prior to study Day 1
2.Multifocal disease, leptomeningeal metastasis, or extracranial metastasis
3.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
4.Left ventricular ejection fraction <40% as determined by ECHO or MUGA
5.Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
6.Know active Chrohn's or other inflammatory bowel disease
7.History of another primary cancer within the 2 years prior to study Day 1, except for the following: nonmelanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer that has been removed or curatively treated
8.A known active acute or chronic infection including, but not limited to, human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) [Patients who have completed a course of anti-viral treatment for HVC are eligible provided than an HCV polymerase chain reaction shows no detectable virus]
9.Pregnant or breastfeeding. 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
10.The presence of any active retinal abnormality determined by screening tests using visual acuity, visual field, fundoscopy, and OCT
11.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
12.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
13.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
14.Minor surgical procedures, fine needle aspirations, or core biopsies within 7 days prior to study Day 1
15.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)
16.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
17.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
18.Concurrent use of prohibited medications: methylprednisolone, prednisone, 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
19.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 wo

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Dose escalation part:<br>1.Assess Safety and tolerability of DSP-0390 in adult patients with recurrent high grade glioma<br>Incidence and severity of TEAEs and SAEs, as assessed by NCI CTCAE<br>2.Determine the MTD and/or RDE<br>Incidence of dose limiting toxicities (DLTs)<br>Dose expansion part: <br>1.Evaluate the preliminary antitumor activity of DSP-0390<br>6 month PFS<br>2.Determine the RP2D

Secondary Outcome Measures

Name	Time	Method

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