Riluzole in Combination With mFOLFOX6 and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

NCT04761614 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-20096NCI-2021-00018
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is to find out the best dose, possible benefits, and/or side effects of riluzole and how well it works in combination with standard of care mFOLFOX6 and bevacizumab in treating patients with colorectal cancer that has spread to other places in the body (metastatic). Riluzole is a well-tolerated oral medication that has demonstrated it may make chemotherapy work better. Chemotherapy drugs, such as oxaliplatin, leucovorin calcium and fluorouracil, work in different ways to stop the growth of \[cancer/tumor\] cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab is an antibody that targets the blood vessel by blocking the activity of a protein called vascular endothelial growth factor alpha (VEGF-A). It helps to make the mFOLFOX6 more effective. Giving riluzole, mFOLFOX6, and bevacizumab may kill more tumor cells compared to mFOLFOX6 and bevacizumab alone in treating patients with colorectal cancer.

Conditions

Metastatic Colorectal Carcinoma; Stage IV Colorectal Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicities (DLTs)

  Will be defined by treatment related grade \>= 4 adverse events or \>= grade 3 alanine aminotransferase or aspartate aminotransferase elevation during the DLT period using the Common Terminology Criteria for Adverse Events version 5.0.

  Up to 4 weeks (2 cycles of treatment) (1 cycle = 14 days)

Secondary Outcomes (2)

• Pharmacokinetic (PK) profile of riluzole (Cmax)

  Day 1 on cycle 1 (each cycle is 14 days)

• Pharmacokinetic (PK) profile of riluzole (AUC)

  Day 1 on cycle 1 (each cycle is 14 days)

Other Outcomes (16)

• Objective response rate (complete response + partial response)

  Up to 112 days

• Change in phosphorylated (p)AKT and pCREB levels

  Up to 42 days (each cycle is 14 days)

• Change in FCGRT/FcRn expression

  Day 1 of cycle 1, 3, 5, 7 (each cycle is 14 days)

Study Arms (1)

Treatment (riluzole, mFOLFOX6, bevacizumab)

EXPERIMENTAL

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.

Biological: Bevacizumab; Drug: Fluorouracil; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Drug: Riluzole

Interventions

Bevacizumab BIOLOGICAL

Given IVPB

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-awwb, Bevacizumab-bvzr, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Mvasi, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, Zirabev

Treatment (riluzole, mFOLFOX6, bevacizumab)

Fluorouracil DRUG

Given IV

Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (riluzole, mFOLFOX6, bevacizumab)

Leucovorin Calcium DRUG

Given IVPB

Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Treatment (riluzole, mFOLFOX6, bevacizumab)

Oxaliplatin DRUG

Given IVPB

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (riluzole, mFOLFOX6, bevacizumab)

Riluzole DRUG

Given PO

Also known as: Rilutek

Treatment (riluzole, mFOLFOX6, bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with metastatic colorectal cancer, who are appropriate candidates to receive mFOLFOX6/bevacizumab. Patients who progressed on FOLFOX-based regimen are allowed
• Willingness to undergo both pre-treatment and post-treatment tumor tissue biopsies (pre-treatment tumor tissue will be sent to pathology lab to confirm metastatic colorectal cancer as the standard of care)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Age \>= 18 years
• Absolute neutrophil count \>= (ANC) 1,500/ul
• Platelets \>= 100,000/ul
• Hemoglobin \>= 9 g/dl
• Serum total bilirubin \< 1.5 x ULN
• Serum albumin \>= 2.5 g/dl
• If no liver involvement, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 1.5 x ULN. If liver involvement, AST and ALT =\< 3.0 x ULN
• Ability to understand and the willingness to sign a written informed consent document
• A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study (and for up to 12 weeks after the last dose of study drug) to minimize the risk of pregnancy. If the partner is pregnant or breastfeeding, the subject must use a condom
• 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

You may not qualify if:

• Patients who are receiving any other investigational agents
• Patients with history of hepatitis B or C
• Patients with severe renal impairment (CrCl \< 30 mL/min)
• Prior full field radiotherapy \< 4 weeks or limited field radiotherapy \< 2 weeks prior to first study drug administration. Patients with central nervous system (CNS) metastases may participate in this trial provided they are clinically stable. Patients who are \< 1 month from radiation therapy must not be included
• Patients with existing grade 2 peripheral neuropathy
• Patients with a history of thrombotic or embolic events within the last six months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism or deep vein thrombosis
• 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

Sponsors & Collaborators

• Ning Jin: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Fluorouracil; dehydroftorafur; Leucovorin; Oxaliplatin; Riluzole

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Thiazoles; Benzothiazoles; Azoles

Study Officials

• Ning Jin, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 21, 2021
• First Posted: February 21, 2021
• Study Start: April 2, 2021
• Primary Completion: April 4, 2023
• Study Completion: May 6, 2023
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)