| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of cancer-related-pain in patients with inadequate pain relief or intolerable side effects when treated with level 3 opioid. |
| Traitement des douleurs cancéreuses chez des patients atteints de douleurs cancéreuses insuffisamment soulagées ou présentant une intolérance aux opioïdes de niveau 3. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Treatment of cancer-related-pain |
| Traitement des douleurs d'origine cancéreuse. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10058019 |
| E.1.2 | Term | Cancer pain |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
| The primary objective is to evaluate clinical effects (success/failure) after level 3 opioids switch to methadone in patients with cancer-related pain inadequately relieved or with intolerable side effects. |
| L'objectif prinicipal est d'évaluer les effets cliniques (succès/échecs) du passage à la méthadone chez des patients insuffisamment soulagées ou présentant une intolérance aux opioïdes de niveau 3. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- Overall safety of methadone during the study (adverse reactions related to methadone and withdrawal symptoms)
- To describe the patients’ characteristics
- To describe the effects of methadone on pain relief
- To describe the methadone administration
- To evaluate patient’s quality of life
- To evaluate the prescriber’s opinion regarding the handling of methadone initiation.
|
Les objectifs secondaires sont :
- Tolérance globale de la méthadone durant l’étude (effets indésirables liés à la méthadone et syndromes de sevrage)
- Décrire les caractéristiques des patients
- Décrire les effets de la méthadone sur le soulagement de la douleur
- Décrire l’administration de la méthadone
- Evaluer la qualité de vie du patient
- Recueillir l’avis du médecin sur la facilité d’initiation de la méthadone. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Adult patient of at least 18 years of age
2. Patient suffering from cancer disease, undergoing chemotherapy treatment or not
3. Patient presenting nociceptive or mixed pains inadequately relieved with level 3 opioids (morphine, oxycodone, transdermal fentanyl, hydromorphone) with a numeric pain scale score ≥5 evidence-based or presenting intolerable side effects with level 3 opioids
4. Patient undergoing level 3 opioid treatment (morphine sulphate or morphine chlorhydrate or fentanyl or oxycodone or hydromorphone)
5. Patient presenting a good understanding of the study objectives and able to give his/her written consent
6. Patient able to communicate with the investigator or his representative
7. Patient available during the whole course of the study and agreeing the study requirements
8. Patient with Social Insurance
9. Patient having received patient’s information form, orally informed and having signed the consent form. |
1. Patient adulte âgé de plus de 18 ans
2. Patient atteint d'un cancer, sous chimiothérapie ou non
3. Patient présentant des douleurs nociceptives ou mixtes mal soulagées par un traitement opioïde de niveau 3 (morphine, oxycodone, fentanyl transdermique, hydromorphone) objectivées par un score sur l’échelle numérique de douleur ≥ 5 ou présentant des effets indésirables intolérables sous traitement opioïde de niveau 3
4. Patient ayant un traitement opioïde de niveau 3 en cours (sulfate de morphine ou chlorhydrate de morphine ou fentanyl ou oxycodone ou hydromorphone)
5. Patient ayant une bonne compréhension des objectifs de l'étude et capable de donner un consentement écrit
6. Patient capable de communiquer avec l'investigateur ou son représentant
7. Patient disponible pendant toute la durée de l'étude et acceptant les exigences de l'étude
8. Patient bénéficiant d’un régime d’Assurance Maladie
9. Patient ayant reçu la note d’information, eu les informations oralement et ayant signé le consentement éclairé. |
|
| E.4 | Principal exclusion criteria |
1. Patient in terminal cancer disease (life expectancy less than 2 months) according to investigator’s judgement
2. Patient treated with a medication that may result in an interaction with methadone, such as: antiarrythmic treatments (Ia or III), erythromycin, spiramycin, intravenous vincamin
3. Patient receiving opioid treatment for any other reason than pain
4. Patient unable to swallow the study treatment
5. Patient presenting contra-indication to the use of methadone
6. Patient having a decompensated respiratory failure or a severe hepatic disease
7. Patient having a known hypersensitivity to methadone
8. Patient presenting QT interval prolongation on ECG results
9. Patient receiving a concomitant treatment with a morphine-type agonist-antagonist medication (pentazocine, buprenorphine, nalbuphine) or with sultropide
10. Patient treated by radiotherapy within 15 days before inclusion
11. Patient participating or having participated in another clinical trial with a new therapy within 1 month before inclusion
12. Patient with a history of substance abuse
13. For woman with childbearing potential: pregnancy or breastfeeding.
14. Forfeiture of freedom or under guardianship
15. Past history of suicidal attempts
16. Patient likely not to respect the study conditions and/or study discontinuation criteria according to investigator’s judgement
17. Patient presenting any other medical condition or illness or clinically significant abnormal findings on the physical examination at screening that, in the opinion of the Investigator, make the patient unsuitable for the study or put the patient at additional risk.
|
1. Patient en phase terminale de cancer (espérance de vie estimée à moins de 2 mois) selon le jugement de l’investigateur
2. Patient traité par un médicament susceptible d'entraîner une interaction avec la méthadone : antiarythmiques (classe la ou III); l'érythromycine, la spiramycine, la vincamine par voie intraveineuse
3. Patient recevant un traitement opioïde pour toute autre raison que le traitement de la douleur
4. Patient incapable d’avaler le traitement de l’étude
5. Patient présentant une contre-indication à l’utilisation de la méthadone
6. Patient présentant une insuffisance respiratoire décompensée ou une insuffisance hépatocellulaire sévère
7. Patient ayant une hypersensibilité connue à la méthadone
8. Patient présentant un allongement de l’intervalle QT à l’ECG
9. Patient ayant un traitement concomitant par un agoniste-antagoniste morphinique (pentazocine, buprénorphine, nalbuphine) ou par sultropide
10. Patient ayant reçu une radiothérapie dans les 15 jours avant l’inclusion
11. Patient participant à un autre essai clinique ou ayant participé à un protocole thérapeutique incluant une nouvelle thérapie dans le mois précédant l’inclusion
12. Patient ayant des antécédents de toxicomanie
13. Pour les femmes en âge de procréer : grossesse en cours ou allaitement
14. Patient privé de liberté ou sous tutelle
15. Patient ayant des antécédents de tentative de suicide
16. Patient susceptible de non-respect des conditions d'étude et/ou de l’arrêt de l'étude selon le jugement de l'investigateur
17. Patient présentant tout antécédent ou pathologie en cours ou tout signe/symptôme cliniquement significatif à l’examen clinique de la sélection qui, selon le jugement de l'investigateur, est incompatible avec une participation du patient à l’étude ou l’expose à des risques additionnels. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The binary main criterion is based on success/failure rate related to methadone switch on D4.
The success is defined as the adequate pain relief on D4 and no occurrence of overdose between D1 and D4. All unmet definitions of success are considered as failures.
The adequate pain relief is defined as the composite criterion:
- Decrease of at least 2 points on the numeric pain scale score from 0 (no pain) to 10 (unacceptable pain) evaluated on D4 when compared to the numeric pain scale score at baseline,
- And a numeric pain scale score <5 during two consecutive days (between D1 and D4).
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The success/failure rate after the switch to methadone will be compared at D4. |
|
| E.5.2 | Secondary end point(s) |
The following parameters will be considered as secondary evaluation parameters:
Safety of methadone:
1 - Adverse event and SAE (type, intensity and number) related to methadone during the study
2 - Evaluation of Handelsman scores assessing the withdrawal syndrome
3 - Percentage of patients with a withdrawal syndrome, if applicable
4 - Change in QT interval
5 - Description of patients’ characteristics (sex, age, primary cancer disease location and metastases, ECOG performance status, previous/current opioid treatments for pain, adverse reactions related to the previous opioid treatment, current anti-cancer treatment)
Effects of methadone on pain relief:
6 - Pain intensity with the numeric pain scale
7 - Pain intensity and pain interference scores from the BPI questionnaire
8 - Percentage of subjects with adequate pain relief
9 - Time to obtain pain relief
Methadone administration:
10 - Mean doses of methadone
11 - Mean number and intensity of breakthrough pain episodes
12 - Number of interdoses for the group “patient-controlled dose”(Group A)
13 - Number of additional doses of methadone for the group “fixed dose” (Group B)
14 - Number of methadone dose adjustment for the group “patient-controlled dose” (Group A)
15 - Mean methadone stabilised dose (defined as a stable dose of methadone for at least two days and less than 4 breakthrough pain episodes per day)
16 - Time to achieve dose stabilization of methadone
17 - Description of adjuvant pain medications and rescue
Quality of life:
18 - Quality of life improvement evaluated with EORTC QLQ-C30 quality of life scale
Prescriber’s opinion:
19 - Prescriber’s opinion regarding the handling of methadone initiation
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
The following parameters will be considered as secondary evaluation parameters:
Safety of methadone:
1 - overall evaluation
2 - overall evaluation
3 - overall evaluation
4 - between D1 and D7
5 – at baseline
Effects of methadone on pain relief:
6 - on D14, D28, D42 and D56
7 - on D-2, D4, D28 and D56
8 - between D4-D14, D14-D28, D28-D42 and D42-D56
9 - overall evaluation
Methadone administration:
10 - between D1-D4, D4-D14, D14-D28, D28-D42 and D42-D56
11 - on D1 to D7, D14, D28, D42 and D56
12 - overall evaluation
13 - between D1 and D3
14 - between D1 and D6
15 - overall evaluation
16 - overall evaluation
17 - overall evaluation
Quality of life:
18 - on D56
Prescriber’s opinion:
19 - overall evaluation |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| 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 | 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) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
| 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
|
| last visit of the last subject |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 0 |
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