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Metastatic Colorectal CarcinomaPhase 1NCT04761614

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

A Phase 1 study testing Bevacizumab, Fluorouracil and Leucovorin Calcium in people with Metastatic Colorectal Carcinoma and Stage IV Colorectal Cancer AJCC v8, run by Ning Jin at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bevacizumab, Fluorouracil and Leucovorin Calcium
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
2 Apr 2021to 6 May 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase I Study of Riluzole in Combination With mFOLFOX6/Bevacizumab in Patients With Metastatic Colorectal Cancer

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Characterize the safety and toxicity of riluzole in combination with modified (m) leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) 6/bevacizumab and determine the recommended phase II dose (RP2D) of riluzole in combination with mFOLFOX6/bevacizumab in patients with metastatic colorectal cancer.

SECONDARY OBJECTIVE:

  1. Determine the pharmacokinetics of riluzole in patients with metastatic CRC.

EXPLORATORY OBJECTIVES:

  1. Assess the efficacy of the combination treatment. II. Determine the effect of riluzole in downstream GRM3 signaling by immunofluorescent staining of phosphorylated (p)AKT and pCREB in pre- and post-treatment tumor tissues.

III. Assess FCGRT/FcRn expression, bevacizumab pharmacokinetics, inflammatory cytokines, and cachexia associated factors as early biomarkers for resistance to therapy.

IV. Assess cytotoxic T cells in peripheral blood to evaluate the immunomodulatory effect of this therapy.

OUTLINE: This is a dose-escalation study of riluzole.

Patients receive riluzole orally (PO) twice daily (BID) on days 1-14. Patients also receive oxaliplatin via intravenous piggyback (IVPB) over 2 hours, leucovorin calcium IVPB over 2 hours, and bevacizumab IVPB over 30 minutes on day 1 and fluorouracil via intravenous (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.

After completion of study treatment, patients are followed up for 30 days.

Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IVPB

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • Leucovorin CalciumDrug

    Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate

    Given IVPB

  • OxaliplatinDrug

    Also called 1-OHP, Ai Heng, Aiheng, Dacotin

    Given IVPB

  • RiluzoleDrug

    Also called Rilutek

    Given PO

Study groups in NCT04761614
Study groupRoleWhat they receive
Treatment (riluzole, mFOLFOX6, bevacizumab)ExperimentalPatients 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.
Receives: Biological: Bevacizumab; Drug: Fluorouracil; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Drug: Riluzole

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (2)

  1. Pharmacokinetic (PK) profile of riluzole (Cmax)

    K data analysis will utilize a nonlinear mixed effects approach whereby PK parameter estimates will be generated from the data, and 'dose day' will be evaluated as a covariate on clearance and volume of distribution. The PK parameters including Cmax. Peak Plasma Concentration (Cmax)

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

  2. Pharmacokinetic (PK) profile of riluzole (AUC)

    PK data analysis will utilize a nonlinear mixed effects approach whereby PK parameter estimates will be generated from the data, and 'dose day' will be evaluated as a covariate on clearance and volume of distribution. The PK parameters including AUC. Area under the plasma concentration versus time curve (AUC)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Feb 2021
  2. Study start2 Apr 2021
  3. Primary completion4 Apr 2023
  4. Study completion6 May 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04761614
Sponsor's protocol ID
OSU-20096
Other IDs
NCI-2021-00018
Status last verified
Mar 2025
First submitted
21 Jan 2021
Last updated
28 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bevacizumab, Fluorouracil and Leucovorin Calcium in people with Metastatic Colorectal Carcinoma and Stage IV Colorectal Cancer AJCC v8, run by Ning Jin at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicities (DLTs) (time frame: Up to 4 weeks (2 cycles of treatment) (1 cycle = 14 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04761614.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2025.

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