Effectiveness Assessment of Riluzole in the Prevention of Oxaliplatin-induced Peripheral Neuropathy.

NCT03722680 | Suspended Phase 2 DMC

• 2 other identifiers: UC-0106/17122017-002320-25
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 16

Brief Summary

It is a phase II trial, randomized, parallel, double blind, multicenter, comparing riluzole versus placebo. The trial population is composed of patients ≥18 years old that have developed stage II/III colorectal cancer and are eligible for Simplified FOLFOX4 (6-12 cycles) adjuvant chemotherapy. The primary objective is to assess the preventive efficacy of riluzole on the severity of oxaliplatin-induced peripheral neuropathy during the Simplified FOLFOX4 adjuvant chemotherapy of stage II/III colorectal cancers.

Conditions

Oxaliplatin-induced Peripheral Neuropathy

Keywords

Riluzole; oxaliplatin; colorectal cancer; neuropathy

Outcome Measures

Primary Outcomes (1)

• Quality of life questionnaire-chemotherapy-induced peripheral neuropathy (QLQ-CIPN20)

  QLQ-CIPN20 Questionnaire (EORTC): Self-reported questionnaire consisting of 20 questions that assess the symptoms and functional limitations of chemotherapy-induced peripheral neuropathy. The questionnaire is divided in 3 subscales: sensory, motor, and autonomic and gives a comprehensive picture of the nature, frequency, and severity of chemotherapy-induced peripheral neuropathy (CIPN). Using a 4-point Likert scale (1 = "not at all," 2 = "a little," 3 = "quite a bit," and 4 = "very much"), patients indicate the degree to which they have experienced sensory, motor, and autonomic symptoms.

  3 months afer initiation of oxaliplatin based chemotherapy (1 cycle = 14 days)

Secondary Outcomes (12)

• QLQ-CIPN20

  At inclusion (V0), 3 months (V2), up to 7 months (V3), up to 9 months (V4), up to 12 months (V5), up to 15 months (V6), and up to 18 months (V7) after initiation of oxaliplatin based chemotherapy.

• National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

  throughout study completion, assessed up to 43 months

• Brief Pain Inventory (BPI) questionnaire

  At inclusion (V0), 3 months (V2), up to 7 months (V3), up to 9 months (V4), up to 12 months (V5), up to 15 months (V6), and up to 18 months (V7) after initiation of oxaliplatin based chemotherapy.

• Douleur Neuropathique 4 (DN4) questionnaire (interview portion)

  This evaluation will be carried out only if the item 5 of BPI "general pain felt in the last 7 days" is ≥4/10.

• Neuropathic Pain Symptom Inventory (NPSI) questionnaire

  This evaluation will be carried out only if the item 5 of BPI "general pain felt in the last 7 days" is ≥4/10.

Study Arms (2)

Riluzole

EXPERIMENTAL

The patient will be taken one tablet twice a day, in the morning and in the evening during the meal (12h interval). The medication is taken during the 14 days of each chemotherapy cycle, beginning 7 days before the start of chemotherapy and ending 2 weeks after the start of last cycle of chemotherapy (25 weeks). The treatment ends with the cessation of chemotherapy (visit V3 or anticipated stop).

Drug: Riluzole

Placebo

PLACEBO COMPARATOR

Posology, administration and duration of treatment will be equivalent to riluzole group.

Drug: Placebo Oral Tablet

Interventions

Riluzole DRUG

Riluzole during chemotherapy (oxaliplatin)

Riluzole

Placebo Oral Tablet DRUG

placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients aged ≥ 18 years old,
• Eligible patient starting adjuvant oxaliplatin-based chemotherapy (6-12 cycles, Simplified FOLFOX4) for stage II/III colorectal cancer,
• Histological or cytological confirmation of colorectal cancer,
• Performance status (ECOG) ≤2,
• Normal hematological function (ANC ≥1.5 x 10⁹/L; platelets count ≥100 x 10⁹/L; hemoglobin ≥9.0 g/dL),
• Normal hepatic function: total bilirubin ≤1.5 x upper limit of normal (ULN) (unless documented Gilbert's syndrome); aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤3 x ULN, and gamma-glutamyltransferase (GGT) ≤3 x ULN,
• Normal renal function: serum creatinine ≤1.5 x ULN,
• Normal cardiac function: ECG,
• Patients affiliated to the French national health insurance,
• Patient must have signed a written informed consent form prior to any study specific procedures,
• French language comprehension,
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

You may not qualify if:

• Metastatic cancer,
• Diagnosis of neuropathy,
• EORTC QLQ-CIPN20 sensory score \>6,
• Previous neurotoxic chemotherapy treatment,
• Patients with chronic obstructive pulmonary disease,
• ALAT/ASAT elevated more than 3 times the normal value,
• Patients with known allergy or severe hypersensitivity to riluzole or any of the study drug excipients,
• Dependence on alcohol or drugs,
• Psychotic disorders,
• Women pregnant or breastfeeding,
• Patients undergoing a measure of legal protection (trusteeship, guardianship ...).

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (16)

ICO - Site Paul Papin

Angers, France

Location

CH Beauvais

Beauvais, France

Location

Centre François Baclesse

Caen, France

Location

Hia Percy

Clamart, France

Location

CHU de Clermont -Ferrand

Clermont-Ferrand, France

Location

Clinique St Côme

Compiègne, France

Location

GHPSO

Creil, France

Location

Centre Georges François Leclerc

Dijon, France

Location

CHU de Dijon

Dijon, France

Location

CH Annecy-Genevois

Pringy, France

Location

CHU de Reims

Reims, France

Location

Institut Jean Godinot

Reims, France

Location

ICO - Site René Gauducheau

Saint-Herblain, France

Location

Hia Begin

Saint-Mandé, France

Location

CHU de Saint-Etienne

Saint-Priest, France

Location

Hôpital Foch

Suresnes, France

Location

Related Publications (1)

• Kerckhove N, Busserolles J, Stanbury T, Pereira B, Plence V, Bonnetain F, Krakowski I, Eschalier A, Pezet D, Balayssac D. Effectiveness assessment of riluzole in the prevention of oxaliplatin-induced peripheral neuropathy: RILUZOX-01: protocol of a randomised, parallel, controlled, double-blind and multicentre study by the UNICANCER-AFSOS Supportive Care intergroup. BMJ Open. 2019 Jun 9;9(6):e027770. doi: 10.1136/bmjopen-2018-027770.

  PMID: 31182448 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

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)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo arm: The patient will be taken on tablet (placebo :50 mg, film-coated tablet) Posology, administration and duration of treatment will be equivalent to riluzole group.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Riluzole arm: The patient will be taken one tablet (riluzole 50 mg, film-coated tablet) twice a day, in the morning and in the evening during the meal (12h interval). The medication is taken during the 14 days of each chemotherapy cycle, beginning 7 days before the start of chemotherapy and ending 2 weeks after the start of last cycle of chemotherapy (25 weeks). The treatment ends with the cessation of chemotherapy (visit V3 or anticipated stop).

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: October 29, 2018
• Study Start: October 28, 2020
• Primary Completion: August 1, 2024
• Study Completion: December 31, 2025
• Last Updated: April 23, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (16)