Clinical trial NCT03722680: Effectiveness Assessment of Riluzole in the Prevention of Oxaliplatin-induced Peripheral Neuropathy.
Official title: Effectiveness Assessment of Riluzole in the Prevention of Oxaliplatin-induced Peripheral Neuropathy: A Phase II Randomized Study by UNICANCER With the Cooperation of AFSOS
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Oxaliplatin-induced Peripheral Neuropathy
Keywords: Riluzole
oxaliplatin
colorectal cancer
neuropathy
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2018-10-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

1. Patients aged ≥ 18 years old,
2. Eligible patient starting adjuvant oxaliplatin-based chemotherapy (6-12 cycles, Simplified FOLFOX4) for stage II/III colorectal cancer,
3. Histological or cytological confirmation of colorectal cancer,
4. Performance status (ECOG) ≤2,
5. Normal hematological function (ANC ≥1.5 x 10⁹/L; platelets count ≥100 x 10⁹/L; hemoglobin ≥9.0 g/dL),
6. 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,
7. Normal renal function: serum creatinine ≤1.5 x ULN,
8. Normal cardiac function: ECG,
9. Patients affiliated to the French national health insurance,
10. Patient must have signed a written informed consent form prior to any study specific procedures,
11. French language comprehension,
12. 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.

Exclusion Criteria:

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

Primary outcomes:
measure: Quality of life questionnaire-chemotherapy-induced peripheral neuropathy (QLQ-CIPN20)
timeFrame: 3 months afer initiation of oxaliplatin based chemotherapy (1 cycle = 14 days)
Secondary outcomes:
measure: QLQ-CIPN20
timeFrame: 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.
measure: National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
timeFrame: throughout study completion, assessed up to 43 months
measure: Brief Pain Inventory (BPI) questionnaire
timeFrame: 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.
measure: Douleur Neuropathique 4 (DN4) questionnaire (interview portion)
timeFrame: This evaluation will be carried out only if the item 5 of BPI "general pain felt in the last 7 days" is ≥4/10.
measure: Neuropathic Pain Symptom Inventory (NPSI) questionnaire
timeFrame: This evaluation will be carried out only if the item 5 of BPI "general pain felt in the last 7 days" is ≥4/10.
measure: QLQ-C30 questionnaire (EORTC)
timeFrame: 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.
measure: Disease progression
timeFrame: From date of randomisation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 43 months.
measure: Time to HRQoL score deterioration
timeFrame: 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.
measure: Quantification of chemotherapy dose reductions
timeFrame: 3 months (V2) and up to 7 months (V3) after initiation of oxaliplatin based chemotherapy.
measure: Quantification of cumulative dose
timeFrame: 3 months (V2) and up to 7 months (V3) after initiation of oxaliplatin based chemotherapy.
measure: Evaluation of study exit rates
timeFrame: 3 months (V2) and up to 7 months (V3) after initiation of oxaliplatin based chemotherapy.
measure: Assessment of glutamate serum level
timeFrame: Glutamate serum level will be dose at inclusion (V0), 3 months (V2), up to 7 months (V3), and up to 18 months (V7) after initiation of oxaliplatin based chemotherapy.
Other outcomes:
Locations:
city: Angers
country: France
facility: ICO - Site Paul Papin
city: Beauvais
country: France
facility: CH Beauvais
city: Caen
country: France
facility: Centre François Baclesse
city: Clamart
country: France
facility: Hia Percy
city: Clermont-Ferrand
country: France
facility: CHU de Clermont -Ferrand
city: Compiègne
country: France
facility: Clinique St Côme
city: Creil
country: France
facility: GHPSO
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Dijon
country: France
facility: CHU de Dijon
city: Pringy
country: France
facility: CH Annecy-Genevois
city: Reims
country: France
facility: CHU de Reims
city: Reims
country: France
facility: Institut Jean Godinot
city: Saint-Herblain
country: France
facility: ICO - Site René Gauducheau
city: Saint-Mandé
country: France
facility: Hia Begin
city: Saint-Priest
country: France
facility: CHU de Saint-Etienne
city: Suresnes
country: France
facility: Hôpital Foch
Study officials:
References:
citation: 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.