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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-02

Study Completion Date

2023-05-06

Brief Summary

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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.

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Detailed Description

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PRIMARY OBJECTIVE:

I. 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:

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

EXPLORATORY OBJECTIVES:

I. 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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (riluzole, mFOLFOX6, bevacizumab)

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.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type BIOLOGICAL

Given IVPB

Fluorouracil

Intervention Type DRUG

Given IV

Leucovorin Calcium

Intervention Type DRUG

Given IVPB

Oxaliplatin

Intervention Type DRUG

Given IVPB

Riluzole

Intervention Type DRUG

Given PO

Interventions

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Bevacizumab

Given IVPB

Intervention Type BIOLOGICAL

Fluorouracil

Given IV

Intervention Type DRUG

Leucovorin Calcium

Given IVPB

Intervention Type DRUG

Oxaliplatin

Given IVPB

Intervention Type DRUG

Riluzole

Given PO

Intervention Type DRUG

Other Intervention Names

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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 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 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 1-OHP Ai Heng Aiheng Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 Rilutek

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No