Trial Title:
Window of Opportunity Study of DSP-0390 in Gliomas
NCT ID:
NCT06636162
Condition:
Glioma, Malignant
Grade II Glioma
IDH Mutation
Conditions: Official terms:
Glioma
Conditions: Keywords:
Grade III Glioma
DSP-0390
IDH-mutant glioma
brain tumor
brain cancer
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Ten patients will be enrolled and treated with DSP-0390, and if the patients tolerate
dosing well, another ten patients will be enrolled and treated with a higher dose of
DSP-0390.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
DSP-0390
Description:
DSP-0390 will be administered orally with preferably 200 mL of water, or approximately
one-half cup water. The patient will take DSP-0390 after a minimum of a 6-hour fast and
will fast for 1 hour after taking the dose.
Arm group label:
DSP-0390 120 mg
Arm group label:
DSP-0390 240 mg
Summary:
This study focuses on determining the pharmacokinetic and pharmacodynamic effect of
DSP-0390 in brain and blood from patients with IDH-mutant WHO grade II or III glioma
undergoing tumor resection. Tissue will be collected during surgical resection. Blood
will be drawn at various time points throughout the 2 weeks of treatment. The hypothesis
is that DSP-0390 will accumulate in brain tumor tissue at pharmacologically relevant
concentrations, and that alterations in cholesterol metabolism driven by mutant IDH will
increase susceptibility to DSP-0390 and lead to tumor cell death.
Criteria for eligibility:
Criteria:
Inclusion Criteria
- Radiologically suspected lower grade glioma, or histologically confirmed
recurrent/residual grade II and III IDH-mutant gliomas.
- Patient must be a candidate for surgical resection where the estimated resected
tumor volume would be at least 8 cc.
- At least 18 years of age.
- Karnofsky ≥ 70%
- Adequate bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1.5 K/cumm (patient may not use G-CSF or GM-CSF to
achieve this ANC level)
- Platelets ≥ 100 K/cumm
- Hemoglobin ≥ 9 g/dL (patient may not receive transfusion or use erythropoietin
to obtain this Hgb level)
- Total bilirubin ≤ 1.5 x IULN (or ≤ 3 x IULN for patients with known Gilbert's
syndrome)
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- International normalized ratio (INR), prothrombin time (PT), partial
thromboplastin time (PTT), or activated partial thromboplastin time (aPTT) ≤1.5
x ULN. 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 Day 1.
- Creatinine Clearance of ≥40 mL/min per Cockroft-Gault formula.
- If a patient is using an antiepileptic medication, the patient is on a stable dose
and without seizures for 14 days prior to Day 1. The antiepileptic medication used
must not fall under any prohibited therapy category as defined in the protocol.
- If the patient is receiving corticosteroids at baseline, the dose administered is
stable or decreasing for at least 5 days prior to Day 1. A higher stable dose of
corticosteroids, if used as hormone replacement therapy, may be allowed upon
discussion with the sponsor-investigator.
- The effects of DSP-0390 on the developing human fetus are unknown. For this reason,
women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry, for
the duration of study participation, and for 6 months after the last dose of study
drug. Should a woman become pregnant or suspect she is pregnant while participating
in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed
consent document.
Exclusion Criteria
- Patient has had prior therapy with bevacizumab or other anti-vascular endothelial
growth factor (VEGF) treatments within 3 months prior to Day 1.
- Patient has multifocal disease, leptomeningeal metastasis, or extracranial
metastasis.
- Patient has a clinically significant abnormal ECG, including those where QT
prolongation (QTcF >450 msec for males and >470 msec for females); and/or the
patient has a history of Torsade de Pointes.
- Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other
condition that may limit the ingestion or gastrointestinal absorption of drugs
administered orally.
- Patient is known to have active Crohn's or other inflammatory bowel disease.
- A history of other malignancy for which all treatment was completed at least 2 years
before Day 1 and the patient has no evidence of disease. Exceptions include
non-melanoma skin cancer, cervical carcinoma in situ, and superficial bladder cancer
that has been removed or curatively treated.
- Currently receiving any other investigational agents.
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to DSP-0390.
- Patient has taken concurrent use of prohibited medications: carbamazepine,
phenytoin, phenobarbital, and other strong or moderate CYP3A4 inhibitors or
inducers, and strong CYP2D6 inhibitors within 1 week or 5 half-lives (whichever is
greater) prior to Day 1 or expects to use them during the study.
- The presence of any active retinal abnormality determined by screening
ophthalmologic examination.
- Patient has significant cardiovascular disease, including New York Heart Association
(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 Day 1.
- Uncontrolled intercurrent illness including, but not limited to, psychiatric
illness/social situations that would limit compliance with study requirements,
disorders associated with significant immunocompromised state, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or
cardiac arrhythmia.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
serum pregnancy test within 7 days prior to the first dose of DSP-0390.
- Patients with HIV are eligible unless their CD4+ T-cell counts are <350 cells/mcL or
they have a history of AIDS-defining opportunistic infection within the 12 months
prior to registration. Concurrent treatment with effective ART according to DHHS
treatment guidelines is recommended. Recommend exclusion of specific ART agents
based on predicted drug-drug interactions (i.e. for sensitive CYP3A4 substrates,
concurrent strong CYP3A4 inhibitors (ritonavir and cobicistat) or inducers
(efavirenz) should be contraindicated.
- Patient has a known detectable viral load for hepatitis C, or evidence of a
hepatitis B surface antigen, all being indicative of active infection.
- Patient has had a major surgical procedure, surgical resection, open biopsy, or
significant traumatic injury within 4 weeks prior to Day 1 or anticipates needing a
major surgical procedure during the course of the study.
- Patient has had a minor surgical procedure, fine needle aspirations, or core
biopsies within 7 days prior to Day 1.
- Patient has evidence of central nervous system hemorrhage on baseline MRI or CT scan
(except for postsurgical, asymptomatic, Grade 1 hemorrhage that has been stable for
at least 4 weeks for enrolled patients).
- Patient has received chemotherapy or investigational anticancer therapy within 4
weeks (except 6 weeks for nitrosoureas and immunotherapy, or 8 weeks for an
implanted nitrosoureas wafer) prior to Day 1.
- Patient has had radiotherapy within 12 weeks prior to 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Contact:
Last name:
Albert H Kim, M.D., Ph.D.
Phone:
314-747-6561
Email:
alberthkim@wustl.edu
Investigator:
Last name:
Albert H Kim, M.D., Ph.D.
Email:
Principal Investigator
Investigator:
Last name:
Ryan Cleary, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Omar H Butt, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Jade Tao, Ph.D.
Email:
Sub-Investigator
Start date:
December 31, 2024
Completion date:
February 14, 2026
Lead sponsor:
Agency:
Washington University School of Medicine
Agency class:
Other
Collaborator:
Agency:
Sumitomo Pharmaceuticals America
Agency class:
Industry
Source:
Washington University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06636162
http://www.siteman.wustl.edu
