Riluzole + Chemotherapy for Colorectal Cancer

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ning Jin

Must not be taking: Investigational agents

Disqualifiers: Hepatitis B/C, Severe renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 9

Duration: 16 weeks

13 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with colorectal cancer that has spread. Researchers aim to determine if adding riluzole, a pill, to a standard chemotherapy mix (mFOLFOX6 and bevacizumab) can enhance cancer cell destruction and improve treatment outcomes. Riluzole may increase chemotherapy effectiveness, while bevacizumab blocks the blood supply to tumors. The trial seeks patients who have previously tried a FOLFOX-based treatment but still have metastatic colorectal cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that riluzole, when combined with mFOLFOX6 and bevacizumab, is generally well-tolerated by patients with advanced colorectal cancer. Studies have found that this combination does not cause unexpected side effects, indicating it can be safely used alongside chemotherapy.

Riluzole is already approved for other conditions, which reassures about its safety. It has been tested in various types of cancer and has shown efficacy without causing major issues. Additionally, the combination of mFOLFOX6 and bevacizumab is a common treatment for colorectal cancer and is known to be safe.

While some side effects may occur, as is common with cancer treatments, research suggests they are manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

Unlike the standard treatments for colorectal cancer, which typically involve chemotherapy combinations like mFOLFOX6 with bevacizumab, this new approach incorporates riluzole, a drug traditionally used in neurological conditions. Researchers are excited about riluzole because it targets glutamate signaling, a pathway not typically addressed in colorectal cancer treatments. By adding riluzole to the mix, there is potential to enhance the effectiveness of chemotherapy and possibly improve patient outcomes by inhibiting cancer cell growth in a novel way.

What evidence suggests that this treatment might be an effective treatment for colorectal cancer?

Research has shown that riluzole might enhance the effectiveness of chemotherapy in treating advanced colorectal cancer. In this trial, participants will receive a combination of riluzole with the chemotherapy drugs mFOLFOX6 and bevacizumab. Studies have found that this combination is generally well-tolerated and may offer benefits. Riluzole seems to help the immune system fight tumors more effectively and slow tumor growth. It has also shown promise as an anti-cancer drug in other types of cancer. These findings suggest that riluzole could potentially enhance the effects of standard chemotherapy treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Ning Jin, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic colorectal cancer who can receive mFOLFOX6/bevacizumab and have adequate organ function. They must understand the study, agree to use contraception, and be willing to undergo tumor biopsies. Excluded are those with hepatitis B/C, severe kidney issues, certain heart conditions, uncontrolled blood pressure or illness that affects compliance.

Inclusion Criteria

Serum total bilirubin < 1.5 x ULN

Ability to understand and the willingness to sign a written informed consent document

I am using birth control and have a negative pregnancy test.

Exclusion Criteria

I have not had extensive radiotherapy in the last 4 weeks or targeted radiotherapy in the last 2 weeks.

My kidney function is severely impaired.

Cardiac conditions as follows: Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction less than 6 months prior to first study drug administration, Class III-IV New York Heart Association (NYHA) congestive heart failure, Uncontrolled hypertension (Systolic blood pressure [BP] > 150 mmHg and diastolic BP > 90 mmHg for 24 hours) despite optimal medical management, Corrected QT (QTc) (Friderica) prolongation > 480 msec, Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, active bleeding diatheses, and psychiatric illness/social situations that would limit compliance with study requirements, Major surgical procedure or significant traumatic injury less than 3 weeks or those who receive minor surgical procedures within 1 week from first dose of study drug administration, Known inability to swallow capsules, Inability to comply with study and/or follow-up procedures, Pregnant women are excluded from this study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive riluzole orally twice daily on days 1-14, and chemotherapy drugs including oxaliplatin, leucovorin calcium, and bevacizumab on day 1, with fluorouracil administered over days 1-2. Treatment repeats every 2 weeks for up to 8 cycles.

16 weeks

8 cycles, each cycle is 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Fluorouracil
• Leucovorin Calcium
• Oxaliplatin
• Riluzole

Trial Overview The trial tests riluzole combined with standard chemotherapy (mFOLFOX6) and bevacizumab against metastatic colorectal cancer. It aims to determine the best dose of riluzole and its effectiveness in enhancing chemotherapy's impact on tumor cells.

How Is the Trial Designed?

Group I: Treatment (riluzole, mFOLFOX6, bevacizumab) Experimental Treatment 5 Interventions

Patients receive riluzole PO BID on days 1-14. Patients also receive oxaliplatin via IVPB over 2 hours, leucovorin calcium IVPB over 2 hours, and bevacizumab IVPB over 30 minutes on day 1 and fluorouracil via IV push over 5 minutes and then IV continuously over 46 hours on days 1-2. Treatment repeats every 2 weeks for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Ning Jin

Lead Sponsor

Trials

1

Recruited

10+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11695182/

Riluzole Enhancing anti-PD-1 Efficacy by Activating cGAS ... Here we have found that riluzole treatment of colon tumors enhances tumor infiltration of CD8+ T cells and inhibits tumor growth in syngeneic immune competent ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.101

A phase I clinical trial of riluzole in combination with ... Conclusions: Our study showed that riluzole plus mFOLFOX6/bevacizumab is well tolerated in patients with metastatic CRC and may have clinical ...

3. aacrjournals.org aacrjournals.org/mct/article/doi/10.1158/1535-7163.MCT-24-0289/748881

Riluzole Enhancing anti-PD-1 Efficacy by Activating cGAS ... This combination showed greater efficacy than either single agent, and strongly suppressed tumor growth in vivo. Taken together, our studies indicate that ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8562386/

Riluzole: A neuroprotective drug with potential as a novel anti ... Riluzole has been proven effective as an anti-neoplastic drug in cancers of various tissue origins, including the skin, breast, pancreas, colon, liver, bone, ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/31/11/2115/762519/Riluzole-in-Combination-with-mFOLFOX6-and

Riluzole in Combination with mFOLFOX6 and Bevacizumab in ... Our study showed that riluzole, in combination with mFOLFOX6/bevacizumab, is tolerable in heavily pretreated patients with metastatic colorectal cancer.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0028390818304040

Targeting the TREK-1 potassium channel via riluzole to ... Riluzole, per se, decreases human colorectal cancer cell line viability in vitro. •. Riluzole, per se, inhibits colorectal polyp development in mice.

7. sciensage.info sciensage.info/index.php/JASR/article/download/2410/1692

Deciphering Riluzole: Illuminating Unexplored Avenues in ... In combination with chemotherapeutic agents, riluzole has synergistic effects in different types of cancers like glioblastoma, colorectal cancer ...