E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute oxaliplatin induced neuropathy |
Acute neuroapthie als gevolg van oxaliplatin |
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E.1.1.1 | Medical condition in easily understood language |
Acute oxaliplatin induced nerve pain |
Acute zenuwpijn als gevolg van oxaliplatin |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
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 |
To evaluate the efficacy of low dose intravenously lidocaine in comparison with placebo in terms of pain relief after the first oxaliplatin administration measured by a numeric rating scale (NRS 0-10 |
Beoordelen van het analgetisch effect van lage dosis intraveneus lidocaïne in vergelijking met placebo na de eerste toediening van oxaliplatin gemeten middels een numerieke beoordelingsschaal (NRS 0-10). |
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E.2.2 | Secondary objectives of the trial |
1. Difference in pain scores between placebo and lidocaine administered concomitant with oxaliplatin during and after all cycles of oxaliplatin administration.
2. Does lidocaine administered attenuates systemic inflammatory response measured by plasma cytokine levels of interleukin (IL)-6, IL-8, IL-10, IL-1β, TNF-α and ICAM-1?
3. To evaluate if lidocaine influences quantative sensory testing (pressure algometry and ice-bucket).
4. To evaluate if lidocaine reduces chronic neuropathic changes measured by the clinical total neuropathy score (TNS), neurophysiologic conductions studies, skin biopsy and measured by a NCI-CTC and EORTC QLQ-CIPN20 questionnaire.
5. Cumulative oxaliplatin dosage.
6. Cumulative analgesics usage.
7. Other secondary outcomes consists of quality of life improvements measured by EORTC QLQ-C30 and patient reported outcome variables for strength and sensory function and DNA/RNA biobanking. |
1. Beoordelen van verschil in pijnscores tijdens en na alle cycli van oxaliplatin tussen placebo en lage dosis intraveneus lidocaïne
2. Verminderd lidocaïne de systemische ontstekingsreactie gemeten door plasma cytokine levels van interleukine (IL) -6, IL-8, IL-10, IL-1β, TNF-α en ICAM-1?
3. Beoordelen of lidocaïne invloed heeft op QST-metingen (druk algometrie en ijswater test).
4. Beoordelen of lidocaïne de chronische neuropathische veranderingen als gevolg van oxaliplatin beïnvloedt, gemeten middels de klinische totale neuropathie score (TNS), neurofysiologische geleidings studies, huid biopsie en middels een NCI-CTC en EORTC QLQ-CIPN20 vragenlijst.
5. Cumulatieve oxaliplatin dosering.
6. Cumulatieve analgetica gebruik.
7. Andere secundaire uitkomstmaten zijn : de kwaliteit van leven gemeten middels de EORTC QLQ-C30 en de patiënt gerapporteerde uitkomstvariabelen voor kracht en sensorische functie en DNA/RNA biobanking |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects with stage II to IV colorectal adenocarcinoma, who are scheduled to receive 6-8 cycles of oxaliplatin 130 mg/m2 every 3 weeks . |
Patiënten met stadium II tot IV colrectaal adenocarcinoom, welke staan gepland voor 6-8 cycli van oxaliplatin elke 3 weken 130mg/m2 |
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E.4 | Principal exclusion criteria |
Receiving other chemotherapeutics in medical history
Allergy to amide type of local anesthetics
Recent myocardial ischemia (<6 months)
Renal function disorders (MDRD < 60)
Liver failure (bilirubine > 1,5x upper limit of normal)
Adequate hematologic parameters
Hypokaliemia
Pregnancy or lactating
Use of anti-arythmic drugs (flecainide)
Pre-existing form of neuropathy (polyneuropathy or small fibre neuropathy)
History of chronic pain and opioid use
Risk factors for CIPN: alcoholism, diabetes mellitus
No written informed consent by patient |
Patiënten die andere chemotherapeutica hebben gehad in verleden
Allergie voor soort lokale anesthetica amide
Recent myocard ischemie (<6 maanden)
Nierfunctiestoornissen (MDRD <60)
Leverfalen (bilirubine> 1,5x bovengrens van normaal)
Adequate hematologische parameters
Hypokaliëmie
Zwangerschap of borstvoeding
Het gebruik van anti-aritmica (bv: flecainide)
Reeds bestaande vorm van neuropathie (polyneuropathie of kleine vezels neuropathie)
Voorgeschiedenis van chronische pijn en het gebruik van opioïden
Risicofactoren voor CIPN: alcoholisme, diabetes mellitus
Geen informed consent verkregen van patiënt |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The difference in NRS scores for pain after the first infusion of oxaliplatin and administration of studymedication.
The aim is a reduction of 3 points of NRS |
Het verschil NRS scores voor pijn na de eerste kuur oxaliplatin en inlopen van de studiemedicatie.
Het doel is een reductie van 3 punten van de NRS |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Directly after administration of the studymedication |
Direct na toedienen van de studiemedicatie |
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E.5.2 | Secondary end point(s) |
1. Difference in pain scores after all cycles of oxaliplatin administration.
2. plasma cytokine levels of interleukin (IL)-6, IL-8, IL-10, IL-1β, TNF-α and ICAM-1 before and after first dose of oxaliplatin?
3. Results from quantative sensory testing (pressure algometry and ice-bucket).
4. Chronic neuropathic changes measured by the clinical total neuropathy score (TNS), neurophysiologic conductions studies, skin biopsy and measured by a NCI-CTC and EORTC QLQ-CIPN20 questionnaire.
5. Cumulative oxaliplatin dosage.
6. Cumulative analgesics usage.
7. Quality of life improvements measured by EORTC QLQ-C30 and patient reported outcome variables for strength and sensory function. |
1. Verschil in pijnscores tijdens en na alle cycli van oxaliplatin
2. plasma cytokine levels van interleukine (IL) -6, IL-8, IL-10, IL-1β, TNF-α en ICAM-1 voor en na eerste oxaliplatin?
3. Invloed op QST-metingen (druk algometrie en ijswater test).
4. chronische neuropathische veranderingen gemeten middels de klinische totale neuropathie score (TNS), neurofysiologische geleidings studies, huid biopsie en middels een NCI-CTC en EORTC QLQ-CIPN20 vragenlijst.
5. Cumulatieve oxaliplatin dosering.
6. Cumulatieve analgetica gebruik.
7. Kwaliteit van leven gemeten middels de EORTC QLQ-C30 en de patiënt gerapporteerde uitkomstvariabelen voor kracht en sensorische functie. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pain scores and patient reported outcomes: before and till 5 days after oxaliplatin infusion
Questionnaires EORTC-CIPN20 and NCI-CTC at baseline, before each oxaliplatin infusion and at 3 months follow up. EORTC QLQ-C30 at baseline at 3 months follow up.
Physical examination (QST, sock/glove like distribution, and clinical total neuropathy score): at baseline, before fourth and eight oxaliplatin infusion and at 3 months follow up
Neurophysiologis studies: at baseline, before fourth and eight oxaliplatin infusion and 3 months follow up
Skin biopt at baseline and at 3 months follow up
Cumulative oxaliplatin dose and analgesics usage at 3 months |
Verschil in NRS vóór en na de volgende oxaliplatin infusies en bij 3 maanden follow up.
Cytokines en ICAM-1: voor en na de 1e infusie van oxaliplatin.
Vragenlijsten: NCI-CTC en EORTC-CIPN20 bij aanvang, vóór elke oxaliplatin infusie en bij 3 maanden follow-up
EORTC QLQ-C30 bij aanvang en 3 maanden follow up.
Patiënt gerapporteerde uitkomsten: bij aanvang, na elke kuur en bij 3 maanden follow up.
Lichamelijk onderzoek:
QST, groote sok/handschoen en klinische totale neuropathie score bij aanvang, vóór 4e en 8e oxaliplatin infusie en bij 3 maanden follow-up.
Neurofysiologische studies
bij aanvang, na de 4e en 8e oxaliplatin infusie en bij 3 maanden follow-up
Huidbiopt op bij aanvang en 3 maanden follow-up
Cumulatieve oxaliplatin dosis en analgetica bij 3 maanden follow-up
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | No |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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The end point of the trial is after the last patient has fully undergone the research procedure. 24 Patients will be included |
Het eindpunt van de studie is nadat de 24e patient de volledige studieprocedure heeft ondergaan |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |