E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034620 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Neuroprotection: Reduction in the risk of occurrence of Grade 3-4 cumulative peripheral sensory neuropathy (PSN) relative to cumulative dose of oxaliplatin. |
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E.2.2 | Secondary objectives of the trial |
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). • Time and 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). |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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. - 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |