Riluzole for Cancer-Related Cognitive Impairment

Overseen By University of California Irvine Medical

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Irvine

Must not be taking: Pixantrone, Cannabis, others

Disqualifiers: Metastasis, Pregnancy, Hepatic impairment, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

51 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the drug riluzole to determine its effectiveness in addressing memory and thinking problems in cancer survivors. The researchers aim to discover if riluzole can improve levels of a brain-supporting protein in individuals who feel their cognitive function has declined since cancer treatment. Participants will be randomly assigned to take either riluzole or a placebo (an inactive substance) for eight weeks. The trial seeks cancer survivors who have experienced memory or thinking difficulties since their treatment, including those who underwent chemotherapy or other cancer therapies in the past three years. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are taking certain drugs like pixantrone, abametapir, cannabis, capmatinib, lapatinib, methotrexate, and levoketoconazole. If you were part of another research study, a 30-day break from those treatments is required.

Is there any evidence suggesting that riluzole is likely to be safe for humans?

Research has shown that riluzole is generally well-tolerated. One study found that taking 100 mg of riluzole daily is "reasonably safe" and can extend the life of patients with ALS (a nerve disease) by a few months. This finding suggests the drug might be safe for other conditions as well.

No severe side effects are commonly reported. However, as with any medication, some individuals might experience mild side effects. For riluzole, these may include nausea or fatigue. Overall, previous studies with other patient groups have considered it safe.

This trial uses a similar dose to what has been used before, so it is expected to be well-tolerated. For any concerns or questions about participation, consulting a doctor is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer-related cognitive impairment?

Most treatments for cancer-related cognitive impairment focus on managing symptoms or using cognitive rehabilitation strategies. But Riluzole works differently, targeting the brain's glutamate system to potentially improve cognitive function. Researchers are excited about Riluzole because it offers a novel approach by modulating glutamate levels, which could address the root cause of cognitive issues rather than just alleviating symptoms. This could lead to more effective and lasting improvements for patients experiencing cognitive difficulties due to cancer.

What evidence suggests that riluzole might be an effective treatment for cancer-related cognitive impairment?

Research has shown that riluzole, which participants in this trial may receive, might improve thinking and memory in cancer survivors experiencing "chemo brain," a type of cognitive impairment. Studies suggest that riluzole could increase levels of brain-derived neurotrophic factor (BDNF), a protein crucial for brain health. Animal studies found that riluzole can lessen the thinking and memory problems caused by chemotherapy. Although researchers are still studying the exact effects of riluzole on these issues in humans, early results are promising and suggest it may enhance brain function. ^{1 2 6 7 8}

Who Is on the Research Team?

Alexandre Chan, PharmD, MPH

Principal Investigator

Chao Family Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for breast cancer survivors over 18 who feel their cognitive abilities have declined since diagnosis or treatment. They must not be undergoing current cancer treatments but should have had past chemotherapy, radiotherapy, or surgery.

Inclusion Criteria

I can understand and agree to the study's procedures and risks.

I feel my thinking skills have declined since my cancer diagnosis or treatment.

I have been diagnosed with breast cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 50 mg of riluzole or placebo twice daily for 8 weeks

8 weeks

3 visits (in-person) at baseline, midpoint, and endpoint

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Riluzole

Trial Overview

The study tests if Riluzole can improve brain function in these individuals compared to a placebo. It's a phase 2a trial where participants are randomly assigned to receive either the drug or an inactive substance without knowing which one they get.

How Is the Trial Designed?

Group I: Riluzole Experimental Treatment 1 Intervention

Study participants randomized to this arm will take 50 mg of riluzole twice daily (every 12 hours) for 8 weeks

Group II: Placebo Placebo Group 1 Intervention

Study participants randomized to this arm will take a placebo, that matches the appearance of 50 mg capsule of riluzole, twice daily (every 12 hours) for 8 weeks

Riluzole is already approved in United States, European Union for the following indications:

Approved in United States as Rilutek for:

• Amyotrophic lateral sclerosis (ALS)

Approved in European Union as Riluzole for:

• Amyotrophic lateral sclerosis (ALS)

Approved in United States as Tiglutik for:

• Amyotrophic lateral sclerosis (ALS)

Approved in United States as Exservan for:

• Amyotrophic lateral sclerosis (ALS)

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Published Research Related to This Trial

Chemotherapy-related cognitive impairment (CRCI), also known as 'chemobrain', affects a significant number of cancer patients, with estimates of occurrence ranging from 17% to 75%.

Factors influencing CRCI include age, education, mental health, treatment regimens, and biological markers, highlighting the need for comprehensive assessment and support from neuropsychologists and oncology nurses to manage this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy-related cognitive impairment. Myers, JS.[2022]

Systemic cancer chemotherapy can lead to long-term cognitive deficits in survivors, affecting areas such as verbal learning, memory, attention, and information processing speed.

There is ongoing research into the mechanisms behind these cognitive deficits, including the potential role of genetic polymorphisms that may increase vulnerability to cognitive decline after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive effects of cytotoxic cancer chemotherapy: predisposing risk factors and potential treatments. McAllister, TW., Ahles, TA., Saykin, AJ., et al.[2019]

A nationwide study involving 580 breast cancer patients showed significant cognitive decline in visual memory and other cognitive domains from prechemotherapy to 6 months postchemotherapy, indicating that cancer-related cognitive impairment (CRCI) is a persistent issue.

In contrast, 363 control participants did not experience cognitive changes over the same period, highlighting the specific impact of chemotherapy on cognitive function in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal Trajectory and Characterization of Cancer-Related Cognitive Impairment in a Nationwide Cohort Study. Janelsins, MC., Heckler, CE., Peppone, LJ., et al.[2022]

Recent prospective trials indicate that patients undergoing chemotherapy can experience specific cognitive impairments, challenging previous beliefs that such dysfunction was not linked to cancer therapy.

Two case studies from a Geriatric Oncology clinic illustrate this issue: a 75-year-old male with lung cancer reported forgetfulness after chemotherapy, and a 65-year-old female with breast cancer experienced cognitive issues following multiple treatments, highlighting the need for awareness and assessment of cognitive health in older cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of cancer therapy on cognition in the elderly. Mandilaras, V., Wan-Chow-Wah, D., Monette, J., et al.[2021]

A pilot study involving 21 breast and gynecologic cancer survivors showed that the Neuroflex cognitive enhancement program is feasible and well-accepted, with participants completing an average of 44.5 hours of training and achieving a 100% completion rate.

Participants reported significant improvements in cognitive function, including verbal learning and memory, as well as mood and disability assessments, suggesting that Neuroflex may effectively address chemotherapy-related cognitive impairment (CRCI).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of focused computerized cognitive training (Neuroflex) to improve symptoms in women with persistent chemotherapy-related cognitive impairment. Vega, JN., Newhouse, PA., Conley, AC., et al.[2023]

Citations

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The study will assess the effects of riluzole on cognitive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB) scores across five ...

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However, its impact on BDNF levels and cognitive function have yet to be explored in cancer patients and survivors. Riluzole may work to improve BDNF levels in ...

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The phase 2a clinical trial is also designed to evaluate the effect of riluzole on cognitive function in these patients over time, said ...

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BDNF Augmentation Using Riluzole Reverses Doxorubicin ...

These cognitive function and anxiety-like behavior data demonstrated that chronic chemotherapy-induced impairments were mitigated by RZ ...

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Riluzole for Cancer-Related Cognitive Impairment

... impairments, challenging previous beliefs that such dysfunction was not linked to cancer therapy. Two case studies from a Geriatric Oncology clinic ...

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The Cochrane review concluded that riluzole 100 mg daily is “reasonably safe and probably prolongs median survival by ~2–3 months” in patients with ALS. It was ...

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An Interventional Pilot Clinical Trial

This is a phase 2a, randomized, double-blinded, placebo-controlled pilot clinical trial determining the impact of riluzole therapy on circulating brain derived ...

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UCI Health

The UCI Health Chao Family Comprehensive Cancer Center has launched the first US clinical trial to investigate the impact of riluzole therapy on circulating ...