A multicenter, randomized double-blind placebo controlled Phase III study of the efficacy of xaliproden in preventing the neurotoxicity of oxaliplatin in first-line treatment of patients with metastatic colorectal cancer treated with oxaliplatin/5-FU/LV. - NA

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2005-002570-30-PT
• Date of registration: 11/11/2005
• Prospective Registration: Yes
• Primary sponsor: Sanofi-Synthelabo Recherche
• Public title: A multicenter, randomized double-blind placebo controlled Phase III study of the efficacy of xaliproden in preventing the neurotoxicity of oxaliplatin in first-line treatment of patients with metastatic colorectal cancer treated with oxaliplatin/5-FU/LV. - NA
• Scientific title: A multicenter, randomized double-blind placebo controlled Phase III study of the efficacy of xaliproden in preventing the neurotoxicity of oxaliplatin in first-line treatment of patients with metastatic colorectal cancer treated with oxaliplatin/5-FU/LV. - NA
• Date of first enrolment: 03/03/2006
• Target sample size: 900
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002570-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Germany, Hungary, Italy, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
- Histologically or cytologically-proven metastatic cancer of the colon or rectum.
- Metastatic disease not curable by surgery or amenable to radiation therapy with
curative intent.
- Male or female aged =18 years.
- WHO Performance Status (PS) : 0 or 1.
- At least one unidimensionally measurable lesion with a diameter =20 mm using
conventional CT or MRI scans or =10 mm using spiral CT scans. If a single lesion is
identified as the target lesion, a histological or cytological confirmation of
adenocarcinoma from that lesion is required.
- No prior chemotherapeutic regimen for metastatic disease.
- Prior adjuvant chemotherapy for non-metastatic disease with 5-FU/LV, with 5-
FU/levamizole, with irinotecan/5-FU/LV, with capecitabine is allowed. In case of
prior adjuvant chemotherapy, the Disease-Free interval from end of the adjuvant
therapy should be greater than 6 months.
- Prior adjuvant chemotherapy with oxaliplatin/5-FU/LV is allowed provided the
progression free interval from end of adjuvant therapy is greater than 12 months.
- Serum creatinine =1.5 X the institution’s ULN.
- Have adequate organ function and be medically stable.
- Signed written informed consent (approved by the Ethics Committee) obtained prior to study-specific screening procedure.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Any condition or past medical history that contra-indicates treatment with oxaliplatin and 5-FU, as reported in approved labeling information.
- Peripheral neuropathy >Grade 1 (as defined by the NCI CTCAE version 3.0).
- Undetectable Sensory Action Potential (SAP) of both sural nerves as shown by the
baseline nerve conduction studies (NCS).
- Concomitant treatments with drugs/ingredients reported to have a potential activity in preventing peripheral sensory neuropathy: Ca/Mg, carbamazepine, amitriptyline, gabapentin, phenytoin, gluthatione, alpha-lipoic acid, celecoxib, amifostine, venlaflaxine, vitamin B1 (thiamine), B6 (pyridoxine).
- Uncontrolled intercurrent illness: e.g. high blood pressure, unstable angina,
symptomatic congestive heart failure (NY Heart Association Classification III or IV),
serious cardiac arrhythmia, diabetes, or active infection.
- Presence of any symptom suggesting brain metastasis.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with metastatic colorectal cancer treated with oxaliplatin/5-FU/LV; at risk of cumulative peripheral sensory neuropathy (PSN) relative to cumulative dose of oxaliplatin.
MedDRA version: 8 Level: LLT Classification code 10034620

Intervention(s)

Product Name: Xaliproden
Product Code: SR57746A
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Xaliproden hydrochloride
CAS Number: 90494-79-4
Current Sponsor code: SR57746A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 1- Main secondary objective:
-Chemotherapy efficacy:
Response Rate (RR) between the control arm A and the experimental arm B in order to ensure that the efficacy of the chemotherapy is not compromised by the addition of xaliproden.

2-Other secondary objectives:
-Neuroprotection:
• Duration of oxaliplatin-induced PSN (Grade 2, 3, 4).
• Overall incidence of PSN during treatment by patient and by grade (Grades 1, 2, 3-4).
• Dose to onset of PSN (Grades 1, 2, 3-4).
• Incidence of dose-reduction and dose-delay due to PSN.
• Incidence of oxaliplatin treatment discontinuation
due to PSN.
• Change in Nerve Conduction Studies (NCS).

-Safety profile (other than PSN)
-Chemotherapy efficacy:
• Progression Free Survival (PFS)
• Overall survival (OS).

Primary end point(s): Primary efficacy endpoint is the probability of occurrence of Grade 3-4 PSN relative
to the cumulative dose of oxaliplatin estimated using the Kaplan-Meier method and compared between the two treatment groups using a 2-sided logrank test
with a type I error of 0.05.

Main Objective: Neuroprotection:
Reduction in the risk of occurrence of Grade 3-4 cumulative peripheral sensory neuropathy (PSN) relative to cumulative dose of oxaliplatin.

Secondary ID(s)

2005-002570-30-GB

EFC5505