What prior FDA approvals exist?

Temozolomide is an FDA-approved drug for the treatment of glioblastoma, often used in combination with radiation therapy. This chemotherapeutic agent is a cornerstone in the management of glioblastoma due to its ability to cross the blood-brain barrier and target tumor cells. The combination of temozolomide with other agents, such as fluoxetine, which induces lysosomal stress, is being studied to enhance its efficacy. Other FDA-approved treatments for brain tumors include bevacizumab, an angiogenesis inhibitor used for recurrent glioblastoma, and carmustine, a nitrosourea alkylating agent.

What other types of research exist?

Promising novel alternatives to Fluoxetine for brain tumor patients include agents targeting the PI3K/PTEN/AKT/mTOR pathway, such as temsirolimus and everolimus, which have shown potential in enhancing chemotherapy efficacy. Additionally, CNS-penetrant tyrosine kinase inhibitors (TKIs) like alectinib and ceritinib are being explored for their effectiveness in brain metastases and may offer new avenues for treatment.

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Alkylating Agent

Fluoxetine + Chemotherapy for Brain Cancer

Q: What side effects are associated with this type of intervention?

Common treatments for brain tumors, such as temozolomide, can cause a range of side effects including nausea, vomiting, fatigue, and myelosuppression (decreased production of blood cells). Temozolomide specifically can also lead to headaches, constipation, and an increased risk of infections due to lowered white blood cell counts. Fluoxetine, primarily used as an antidepressant, may cause side effects such as insomnia, dizziness, drowsiness, and gastrointestinal disturbances. When used together, these treatments aim to enhance the efficacy of chemotherapy but may also compound some of these side effects.

Phase < 1

Recruiting

Led By Mustafa Khasraw, MBChB, MD, FRCP, FRACP

Research Sponsored by Duke University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 month

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether fluoxetine, a common antidepressant, can help improve the effectiveness of a chemotherapy drug called temozolomide (TMZ) in patients with recurrent brain cancer. The study focuses on patients whose cancer has returned and who are undergoing surgery. Fluoxetine is thought to make certain cell parts work harder, which helps TMZ kill cancer cells more effectively. Fluoxetine (Prozac) is one of the most frequently prescribed antidepressants in the United States and has been studied for its effects on depression in cancer patients.

Who is the study for?

Adults over 24 with recurrent glioma brain tumors suitable for surgery and repeat chemo with Temozolomide can join. They must be fairly active (KPS > 70%), have good organ function, and agree to use contraception if needed. Excluded are those on antidepressants within a year, other psychotropics recently, history of mood disorders, certain cancers, pregnant or breastfeeding women, specific tumor locations or conditions deemed unsafe by surgeons.

What is being tested?

The trial tests whether Fluoxetine causes stress in cell structures called lysosomes in the brain which might help Temozolomide work better against cancer cells. Participants will take Fluoxetine before their scheduled surgery where researchers will compare tissue samples from before and after starting the drug.

What are the potential side effects?

Fluoxetine may cause digestive issues, sleep disturbances, sexual dysfunction, anxiety or nervousness; it could also affect blood sugar levels or lead to eye problems like glaucoma. Temozolomide's side effects include nausea, fatigue, hair loss and increased risk of infections due to lowered white blood cell counts.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 month

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 month

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 month for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in LAMP1 expression in tumor samples obtained pre-resection via biopsy and during surgery

Secondary study objectives

Intra-tumoral levels of fluoxetine using LC-MS/MS quantification

Intra-tumoral levels of norfluoxetine using LC-MS/MS quantification

Proportion of patients with partial or complete response at the time of surgical resection

+2 more

Side effects data

From 2012 Phase 4 trial • 43 Patients • NCT00245635

Weight Loss

Stomach Pains

Silliness/Feeling too happy

Trouble Sleeping

Nausea

Menstrual Cramps

Insomnia

Nightmares

Emotional

Suicidal Behavior

Lit Paper on Fire

Fatigue

Decreased Appetite

Sweating

Agitated/Restlessness

Dry Mouth

Headache

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

Fluoxetine

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Fluoxetine pre-surgeryExperimental Treatment1 Intervention

Patients randomized to the experimental arm will receive fluoxetine at 20 mg/day for 5 days (initiation dose) followed by a maintenance dose of 40 mg/day starting on Day 6 (dose level 1) or 60 mg/day starting on Day 6 (dose level 2).

Group II: Temozolomide pre-surgeryActive Control1 Intervention

Temozolomide pre-surgery (control) arm will receive 50 mg/m2 temozolomide daily for 7 days (Days 1-7), followed by resection or biopsy 21 days after initiation of the temozolomide cycle.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fluoxetine

2005

Completed Phase 4

~2370

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for brain tumors include chemotherapy, radiation therapy, and targeted drug therapies. Chemotherapy agents like temozolomide work by damaging the DNA of cancer cells, leading to cell death. Radiation therapy uses high-energy particles to destroy cancer cells by damaging their DNA. Targeted therapies, such as those involving fluoxetine, aim to enhance the effectiveness of chemotherapy by inducing lysosomal stress, which disrupts cellular processes and makes cancer cells more susceptible to treatment. Understanding these mechanisms is crucial for brain tumor patients as it helps in selecting the most effective treatment strategy, potentially improving outcomes and reducing side effects.

Local delivery methods of therapeutic agents in the treatment of diffuse intrinsic brainstem gliomas.Low-grade gliomas: clinical and pathobiological aspects.