ACTIVE_NOT_RECRUITING

Evaluation of Fluoxetine and Cytotoxic Lysosomal Stress in Glioma (FLIRT)

Conditions

Primary Brain Tumor Brain Tumor, Recurrent Brain tumor Fluoxetine Prozac Recurrent Glioma Temozolomide Tumor resection Tumor biopsy Mustafa Khasraw Pro00110628

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2023-08-05

Study Completion:2027-06-05

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05634707

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:24 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age ≥ 24 years of age Note: Fluoxetine has a warning about suicidal thoughts in children, adolescents, and young adults. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24. 2. Patients with recurrent glioma 3. Tumor volume ≥ 1 cm3 4. Clinical indication for craniotomy for biopsy and resection of the lesion 5. Clinical indication for repeat treatment with Temozolomide 6. Karnofsky Performance Status (KPS) \> 70% 7. Adequate organ function: platelets \> 100,000/µL, hemoglobin \>9 gm/dL, ANC \> 1000/µL; creatinine \< 1.5x upper limit of normal (ULN), total bilirubin \< 1.5x ULN, AST/ALT \< 2.5x ULN within 72 hours prior to first administration of Fluoxetine 8. Able to undergo MRI brain with and without contrast 9. If the patient is a sexually active female of childbearing potential, whose partner is male, or if the patient is a sexually active male, whose partner is a female of childbearing potential, the patient must use appropriate contraceptive measures for the duration of the treatment and for 6 months afterwards. Female patients of childbearing potential must have a negative serum pregnancy test at the time of screening and within 48 hours of starting the infusion of the study drug. 10. Signed informed consent approved by the Institutional Review Board	1. Patients currently taking or who have taken any other anti-depressant medication within the past year 2. Patients currently taking psychotropic agents or who have taken other psychotropic agents within the past 7 days 3. Patients with any history of mood/psychotic/substance use disorders 4. Prior, unrelated malignancy requiring current active treatment except for cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin 5. Patients who are pregnant or breastfeeding 6. Patients with contrast-enhancing tumor crossing the midline, multifocal tumor, infratentorial tumor, tumor in eloquent brain regions, extensive tumor dissemination (subependymal or leptomeningeal), or in unsafe brain regions per the opinion of the treating neurosurgeon 7. Patients with worsening neurologic deficits, clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment 8. Unstable systemic disease in the opinion of the treating physician 9. Less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation of recurrent tumor 10. Treated with immunotherapeutic agents within 4 weeks, alkylating agents within 4 weeks, nitrosoureas within 6 weeks, or non-alkylating chemotherapy within 2 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy 11. Treated with antiangiogenic agents (i.e., bevacizumab) within 4 weeks before biopsy 12. Patients who have developed disease progression while receiving temozolomide treatment are not eligible 13. Patients with allergy to fluoxetine 14. Patients with known cardiac disease, predisposing to long QT syndrome 15. Patients with diabetes mellitus, epilepsy, history of bleeding disorders, history of mania or susceptibility to angle-closure glaucoma 16. Patients with a history or who develop significant hyponatremia (serum sodium less than 130mmol/L) 17. Patients with a history of bipolar disorder or schizoaffective disorder 18. Patients with a history of seizure disorder prior to onset of their primary glioma 19. Patients who are currently taking or have taken in the past 2 months: Monoamine Oxidase Inhibitors (MAOI), Pimozide, Thioridazine, Drugs metabolized by the CYP2D6 pathway, Tricyclic Antidepressants, Antipsychotics, Serotonergic Drugs, Triptans, Tryptophan, Anticoagulant drugs (e.g., NSAIDs, aspirin, warfarin), Olanzapine 20. Patients who demonstrated thrombocytopenia following prior treatment with TMZ (platelets \< 50,000/µL)

Inclusion Criteria

Exclusion Criteria

1. Age ≥ 24 years of age Note: Fluoxetine has a warning about suicidal thoughts in children, adolescents, and young adults. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24.
2. Patients with recurrent glioma
3. Tumor volume ≥ 1 cm3
4. Clinical indication for craniotomy for biopsy and resection of the lesion
5. Clinical indication for repeat treatment with Temozolomide
6. Karnofsky Performance Status (KPS) \> 70%
7. Adequate organ function: platelets \> 100,000/µL, hemoglobin \>9 gm/dL, ANC \> 1000/µL; creatinine \< 1.5x upper limit of normal (ULN), total bilirubin \< 1.5x ULN, AST/ALT \< 2.5x ULN within 72 hours prior to first administration of Fluoxetine
8. Able to undergo MRI brain with and without contrast
9. If the patient is a sexually active female of childbearing potential, whose partner is male, or if the patient is a sexually active male, whose partner is a female of childbearing potential, the patient must use appropriate contraceptive measures for the duration of the treatment and for 6 months afterwards. Female patients of childbearing potential must have a negative serum pregnancy test at the time of screening and within 48 hours of starting the infusion of the study drug.
10. Signed informed consent approved by the Institutional Review Board

1. Patients currently taking or who have taken any other anti-depressant medication within the past year
2. Patients currently taking psychotropic agents or who have taken other psychotropic agents within the past 7 days
3. Patients with any history of mood/psychotic/substance use disorders
4. Prior, unrelated malignancy requiring current active treatment except for cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
5. Patients who are pregnant or breastfeeding
6. Patients with contrast-enhancing tumor crossing the midline, multifocal tumor, infratentorial tumor, tumor in eloquent brain regions, extensive tumor dissemination (subependymal or leptomeningeal), or in unsafe brain regions per the opinion of the treating neurosurgeon
7. Patients with worsening neurologic deficits, clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
8. Unstable systemic disease in the opinion of the treating physician
9. Less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation of recurrent tumor
10. Treated with immunotherapeutic agents within 4 weeks, alkylating agents within 4 weeks, nitrosoureas within 6 weeks, or non-alkylating chemotherapy within 2 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy
11. Treated with antiangiogenic agents (i.e., bevacizumab) within 4 weeks before biopsy
12. Patients who have developed disease progression while receiving temozolomide treatment are not eligible
13. Patients with allergy to fluoxetine
14. Patients with known cardiac disease, predisposing to long QT syndrome
15. Patients with diabetes mellitus, epilepsy, history of bleeding disorders, history of mania or susceptibility to angle-closure glaucoma
16. Patients with a history or who develop significant hyponatremia (serum sodium less than 130mmol/L)
17. Patients with a history of bipolar disorder or schizoaffective disorder
18. Patients with a history of seizure disorder prior to onset of their primary glioma
19. Patients who are currently taking or have taken in the past 2 months: Monoamine Oxidase Inhibitors (MAOI), Pimozide, Thioridazine, Drugs metabolized by the CYP2D6 pathway, Tricyclic Antidepressants, Antipsychotics, Serotonergic Drugs, Triptans, Tryptophan, Anticoagulant drugs (e.g., NSAIDs, aspirin, warfarin), Olanzapine
20. Patients who demonstrated thrombocytopenia following prior treatment with TMZ (platelets \< 50,000/µL)

Contacts and Locations

Principal Investigator

Mustafa Khasraw, MBChB, MD, FRCP, FRACP

PRINCIPAL_INVESTIGATOR

Duke University

Study Locations (Sites)

UC San Diego Moores Cancer Center

San Diego, California, 90074-1539

United States

Stanford Cancer Institute

Stanford, California, 94305

United States

NYU Langone Health

New York, New York, 10016

United States

The Preston Robert Tisch Brain Tumor Center at Duke University

Durham, North Carolina, 27710

United States

Collaborators and Investigators

Sponsor: Duke University

Mustafa Khasraw, MBChB, MD, FRCP, FRACP, PRINCIPAL_INVESTIGATOR, Duke University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-08-05

Study Completion Date2027-06-05

Study Record Updates

Study Start Date2023-08-05

Study Completion Date2027-06-05

Terms related to this study

Keywords Provided by Researchers

Brain tumor
Fluoxetine
Prozac
Recurrent
Glioma
Temozolomide
Tumor resection
Tumor biopsy
Mustafa Khasraw
Pro00110628

Additional Relevant MeSH Terms

Primary Brain Tumor
Brain Tumor, Recurrent