Ignite Creation Date:
2024-05-06 @ 6:22 PM
Last Modification Date:
2024-10-26 @ 2:46 PM
Study NCT ID:
NCT05634707
Status:
RECRUITING
Last Update Posted:
2024-02-20
First Post:
2022-11-22
Brief Title:
Evaluation of Fluoxetine and Cytotoxic Lysosomal Stress in Glioma FLIRT
Sponsor:
Duke University
Organization:
Duke University
Study Overview
Official Title:
A Randomized Surgical Window of Opportunity Study With Dose Escalation to Evaluate Whether Oral Fluoxetine Can Induce Cytotoxic Lysosomal Stress and Enhance Temozolomide Efficacy in Clinical Glioma
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this research study is to determine if fluoxetine increases lysosomal stress in patients with recurrent IDHwt glioma by evaluating LAMP1 expression in tumor samples obtained pre-resection via biopsy and during surgery Lysosomes are organelles structures in cells that contain digestive enzymes substances that break down chemicals that help keep the cells free of extra or worn out cell parts Fluoxetine a drug approved by the FDA to treat problems like depression and anxiety can cause changes to structures in cells called lysosomes that then improve how well the chemotherapy drug temozolomide TMZ kills cancer cells in the brain
Detailed Description:
The purpose of this study is to determine whether oral fluoxetine can induce lysosomal stress and enhance Temozolomide TMZ-induced cell death in patients diagnosed with recurrent malignant glioma The primary objective is to determine if fluoxetine increases lysosomal stress in patients with recurrent IDHwt glioma by evaluating LAMP1 expression in tumor samples obtained pre-resection via biopsy and during surgery Following consent an optional biopsy may be performed to confirm recurrence of high-grade glioma Recurrent glioma patients for whom retreatment with TMZ is appropriate and who are able to undergo tumor resection after 1 cycle of temozolomide will be enrolled in this study Following enrollment patients will randomly be assigned to 12 a study arm control n10 or experimental n20 Within the experimental arm two maintenance dose levels of fluoxetine are planned - 40mg OD n10 and 60mg OD n10 Patients randomized to the control arm will receive only 50 mgm2 TMZ daily for 7 days Days 6-12 followed by resection 21 days after initiation of the TMZ cycle Patients randomized to the experimental arm will receive fluoxetine at 20 mgday for 5 days loading initiation dose followed by a maintenance dose of 40 mgday starting on Day 6 dose level 1 or 60 mgday starting on Day 6 dose level 2 This truncated initiation period of fluoxetine has been discussed with the psychiatry department at Duke University Hospital and has been judged to be safe given the additional monitoring precautions that are being included as part of this study On Day 6 patients will start treatment with 50 mgm2 TMZ daily for 7 days Days 6-12 Resection will occur 21 days after initiation of the TMZ cycle on Day 27 Patients will remain on their assigned dose of fluoxetine through resection and follow-up as long as the treatment regimen is tolerated The change between baseline and post-resection will be computed to determine if co-administration of fluoxetine and TMZ will result in increased expression of LAMP1 on resected glioma cells Within each group a Wilcoxon signed-rank test will be conducted to determine if there are significant within group changes A Kruskal-Wallis test will compare the three patient groups Control Group Fluoxetine Group low-dose Fluoxetine Group high-dose with respect to these changes If data suggests that parametric method are appropriate then analysis of variance and a paired t-test will be conducted Risks commonly associated with fluoxetine include nausea diarrhea lack of appetite dry mouth upset stomach or heartburn constipation insomnia anxiety nervousness drowsiness tremor unusual dreams headaches dizziness yawning swelling of face low body temperature sexual dysfunction rash hives and itching sweating flu-like symptoms sore throat stuffy nose and fever
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None