What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as the mFOLFOX6 regimen (which includes fluorouracil, leucovorin, and oxaliplatin) and bevacizumab, have several known side effects. Fluorouracil can cause diarrhea, nausea, vomiting, stomatitis, and hand-foot syndrome. Oxaliplatin is associated with peripheral neuropathy, which can be long-lasting, as well as neutropenia and gastrointestinal symptoms. Bevacizumab, a targeted therapy, can lead to hypertension, increased risk of bleeding, and gastrointestinal perforation. These treatments can also cause fatigue and alopecia. Combining these agents with riluzole aims to enhance chemotherapy efficacy, but the side effects of riluzole itself are not detailed in the provided context.

What prior FDA approvals exist?

The FDA has approved several treatments for colorectal cancer, particularly focusing on chemotherapy and targeted therapies. Key drugs include oxaliplatin, fluorouracil (5-FU), and leucovorin, which are components of the mFOLFOX6 regimen. Bevacizumab, an antibody targeting VEGF-A, is also approved and often used in combination with chemotherapy to inhibit tumor blood vessel growth. These treatments aim to stop cancer cell growth, division, and spread, and are similar to the regimen being studied with riluzole to enhance chemotherapy efficacy.

What other types of research exist?

Promising novel alternatives to Riluzole for enhancing chemotherapy efficacy in colorectal cancer patients include: 1) Immunotherapy agents such as pembrolizumab and nivolumab, which have shown efficacy in combination with chemotherapy. 2) Targeted therapies like bevacizumab and cetuximab, which are often used alongside chemotherapy to improve outcomes. 3) Novel agents like TAS-102 (trifluridine/tipiracil) and regorafenib, which have been used in refractory cases and may offer benefits when combined with standard chemotherapy regimens.

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Monoclonal Antibodies

Riluzole + Chemotherapy for Colorectal Cancer

Q: What is the mechanism of action of this treatment?

Common treatments for colorectal cancer include chemotherapy agents like oxaliplatin, leucovorin, and fluorouracil, as well as targeted therapies such as bevacizumab. Oxaliplatin works by causing DNA crosslinking and damage, which inhibits cancer cell replication. Leucovorin enhances the effectiveness of fluorouracil, which disrupts DNA synthesis and repair by inhibiting the enzyme thymidylate synthase. Bevacizumab is an antibody that targets and inhibits vascular endothelial growth factor (VEGF), reducing blood supply to tumors and inhibiting their growth. These mechanisms are crucial for colorectal cancer patients as they target cancer cells directly and disrupt the tumor's ability to grow and spread, potentially improving survival rates and quality of life.

Phase 1

Waitlist Available

Led By Ning Jin, MD

Research Sponsored by Ning Jin

Eligibility Criteria Checklist

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

Must have

Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy. WOCBP must have a negative serum or urine pregnancy test within 72 hours before the start of the investigational product

Age >= 18 years

Must not have

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

Patients with severe renal impairment (CrCl < 30 mL/min)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day 1 of cycle 1,3,5,7 (each cycle is 14 days)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether adding riluzole to standard chemotherapy and bevacizumab can better treat patients with colorectal cancer that has spread. Riluzole may enhance the effectiveness of chemotherapy, which kills or stops cancer cells, while bevacizumab cuts off the tumor's blood supply. Bevacizumab has been shown to improve survival in patients with advanced colorectal cancer when combined with chemotherapy.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions related to immune system suppression such as increased risk of infection, liver toxicity indicated by elevated bilirubin levels, nerve damage presenting as peripheral neuropathy, fatigue from anemia due to low hemoglobin levels, and bleeding risks associated with low platelet counts.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am 18 years old or older.

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I am fully active or can carry out light work.

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I agree to have tissue samples taken before and after treatment to confirm my colorectal cancer.

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My liver enzymes are within the normal range for my condition.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My kidney function is severely impaired.

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I have moderate numbness or pain in my hands or feet.

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I have had hepatitis B or C in the past.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 1 of cycle 1,3,5,7 (each cycle is 14 days)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day 1 of cycle 1,3,5,7 (each cycle is 14 days)

This trial's timeline: 3 weeks for screening, Varies for treatment, and day 1 of cycle 1,3,5,7 (each cycle is 14 days) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Dose limiting toxicities (DLTs)

Secondary study objectives

Pharmacokinetic (PK) profile of riluzole (AUC)

Pharmacokinetic (PK) profile of riluzole (Cmax)

Other study objectives

C-reactive protein

Change in FCGRT/FcRn expression

Change in bevacizumab clearance (AUC)

+13 more

Side effects data

From 2008 Phase 4 trial • 26 Patients • NCT00419003

38%

Fatigue

38%

Headache

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

Placebo Pre-Treatment

Lamotrigine Pre-Treatment

Riluzole Group

Ketamine

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (riluzole, mFOLFOX6, bevacizumab)Experimental Treatment5 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bevacizumab

2013

Completed Phase 4

~5540

Leucovorin Calcium

2011

Completed Phase 3

~12500

Oxaliplatin

2011

Completed Phase 4

~2890

Fluorouracil

2014

Completed Phase 3

~11700

Riluzole

2006

Completed Phase 4

~2780

0 / 9Eligibility criteria met

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 colorectal cancer include chemotherapy agents like oxaliplatin, leucovorin, and fluorouracil, as well as targeted therapies such as bevacizumab. Oxaliplatin works by causing DNA crosslinking and damage, which inhibits cancer cell replication. Leucovorin enhances the effectiveness of fluorouracil, which disrupts DNA synthesis and repair by inhibiting the enzyme thymidylate synthase. Bevacizumab is an antibody that targets and inhibits vascular endothelial growth factor (VEGF), reducing blood supply to tumors and inhibiting their growth. These mechanisms are crucial for colorectal cancer patients as they target cancer cells directly and disrupt the tumor's ability to grow and spread, potentially improving survival rates and quality of life.