| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with BRAF V600 mutation positive |
| Patients atteints de mutation BRAF V600 positif |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with BRAF V600 mutation positive |
| Patients atteints de mutation BRAF V600 positif |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10027481 |
| E.1.2 | Term | Metastatic melanoma |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 long term safety as assessed by the occurrence of AEs/SAEs. |
| Evaluation de l’innocuité à long terme du traitement sur la base de la survenue des effets indésirables, graves ou non. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective of the study is to evaluate clinical benefit as assessed by the Investigator. Proportion of patients with clinical benefit as assessed by the Investigator will be summarized at scheduled visits using FAS. |
| Evaluation du bénéfice clinique par le médecin-investigateur. Proportion de patients tirant un bénéfice clinique selon le médecin-investigateur aux visites prévues par le protocole. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Patient is currently receiving treatment with dabrafenib/trametinib monotherapy or combination within a Novartis or former GSK sponsored study which has fulfilled the requirements for the primary objective.
2. In the opinion of the Investigator would benefit from continued treatment.
3. Patient has demonstrated compliance, as assessed by the Investigator, within the parent study protocol requirement(s).
4. Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures.
5. Written informed consent obtained prior to enrolling in the roll-over study and receiving study medication. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
6. If the patient is a minor, the parent who signs the consent for the minor must be a legally recognized parent or guardian. Where deemed appropriate by the Investigator, and the child’s parent or guardian, the child will also be included in the all discussions about the trials and the minor’s assent if 7 years or older will be obtained.
7. Does not require treatment with prohibited concomitant medications |
Les patients éligibles pour être inclus dans cette étude doivent remplir tous les critères suivants :
1. Patients recevant actuellement du dabrafenib et/ou du trametinib dans le cadre d’une étude sponsorisée par Novartis ou GSK ayant satisfait les exigences de l’objectif principal.
2. Patients tirant un bénéfice de la poursuite du traitement, selon le médecin-investigateur.
3. Patients ayant respecté les exigences du protocole de l’étude parent, selon l’appréciation du médecin-investigateur.
4. Patients ayant la volonté et la capacité de respecter le calendrier des visites, les modalités du traitement et toute autre procédure de l’étude.
5. Patients ayant donné leur consentement éclairé par écrit avant d’être inclus dans l’étude d’extension et avant de recevoir le traitement à l’étude. Si le consentement ne peut pas être donné par écrit, le consentement non écrit devra être formellement documenté en présence d’un témoin, idéalement impartial et digne de confiance.
6. Si le patient est mineur, le parent signant le consentement doit être un parent ou un tuteur légal. Si jugé approprié par le médecin-investigateur et le parent ou le tuteur, le patient mineur sera inclus dans toutes les discussions concernant l’étude. Il devra donner son assentiment s’il a au moins 7 ans.
7. Patients ne nécessitant pas de traitement concomitant interdit (voir Section 6.4.3 du protocole). |
|
| E.4 | Principal exclusion criteria |
Patients eligible for this study must not meet any of the following criteria:
1. Patient has been previously permanently discontinued from study treatment in the parent protocol due to any reason.
2. Patient’s indication is commercially available and reimbursed in the local country.
3. Patient has participated in a combination trial where dabrafenib and/or trametinib was dispensed in combination with another study medication.
4. Patient currently has unresolved toxicities for which dabrafenib and/or trametinib dosing has been interrupted in the parent study.
5. Pregnant or nursing (lactating) women Female patients who are lactating must discontinue nursing prior to the first dose of study treatment and must refrain from nursing throughout the treatment period and for 4 months following the last dose of study treatment.
6. Concurrent treatment with other systemic anti-cancer therapies is not allowed (e.g., chemotherapy, immune, biologic, or targeted therapy), with the exception of radiotherapy.
7. Female patient is of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 150-days after stopping treatment. Highly effective contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
• Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject.
• Placement of a non-hormonal intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year.
• Double-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/cream/suppository).
Note: Hormonal-based methods (e.g., oral contraceptives) are not considered as highly effective methods of contraception due to potential drug-drug interactions with dabrafenib.
8. Sexually active males unless they use a condom during intercourse while on treatment and for 150 days after stopping treatment should not father a child in this period. A condom is required to be used by vasectomized men as well during intercourse in order to prevent delivery of the drug via semen.
9. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. |
Les patients éligibles pour cette étude ne devront répondre à aucun des critères suivants :
1. Patients dont le traitement a définitivement été arrêté dans le cadre de l’étude parent, pour quelque raison que ce soit.
2. Patients atteints d’une maladie pour laquelle le traitement est approuvé et remboursé dans leur pays.
3. Patients ayant participé à une étude au cours de laquelle ils ont reçu du dabrafenib et/ou du trametinib associé(s) à un autre traitement.
4. Patients présentant actuellement des effets indésirables non résolus pour lesquels le traitement par dabrafenib et/ou trametinib a dû être interrompu dans l’étude parent.
5. Femmes enceintes ou qui allaitent. L’allaitement doit être arrêté avant la première dose de traitement à l’étude et ne pas être repris pendant l’étude et pendant les 4 mois suivant la dernière dose de traitement à l’étude.
6. Le traitement concomitant par d’autres anticancéreux systémiques n’est pas autorisé (par ex. chimiothérapie, immunothérapie, traitement biologique ou ciblé), à l’exception de la radiothérapie.
7. Les femmes en mesure d’avoir des enfants, c’est-à-dire toutes les femmes physiologiquement aptes à être enceintes, sauf si elles utilisent une méthode de contraception très efficace pendant tout le traitement et pendant 150 jours après l’arrêt du traitement.
Les méthodes de contraception très efficaces incluent :
• Abstinence totale (lorsque cela est en accord avec les préférences et le style de vie de la patiente). L’abstinence périodique (par ex. en appliquant les méthodes de calendrier, d’ovulation, de température, ou de post-ovulation) et le retrait ne sont pas considérés comme des méthodes de contraception acceptables.
• Placement d’un dispositif ou système intra-utérin non-hormonal ayant un taux d’échec < 1 % par an.
• Double contraception : préservatif et cape occlusive (diaphragme ou cape cervicale) associé avec un spermicide vaginal (en gel, crème, mousse ou ovule).
Remarque : Les méthodes de contraception hormonale (par ex. : contraceptifs oraux) ne sont pas autorisées car non considérées comme des méthodes très efficaces du fait des interactions médicamenteuses possibles avec le dabrafenib.
8. Les hommes ayant des rapports sexuels sauf s’ils utilisent un préservatif et ne conçoivent pas d’enfant pendant le traitement à l’étude et pendant les 150 jours qui suivent l’arrêt du traitement. Les hommes vasectomisés doivent également utiliser des préservatifs pour éviter la transmission du médicament durant les rapports via le sperme.
9. Les femmes sont considérées comme post-ménopausées et non aptes à avoir des enfants si elles ont eu 12 mois d’aménorrhée spontanée avec un profil clinique approprié (par ex. âge approprié, antécédents de symptômes vasomoteurs) ou si elles ont eu une ovariectomie bilatérale (avec ou sans hystérectomie), une hystérectomie totale ou une ligature des trompes au moins 6 semaines auparavant. Dans le cas d’une ovariectomie seule, le statut reproductif de la femme devra être confirmé par un suivi du niveau hormonal. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Frequency and severity of AEs/SAEs |
| Fréquence et sévérité des effets indésirables, graves ou non. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Primary endpoints will be evaluated throughout the study. |
| Les critères finaux seront évalués tout au long de l'étude. |
|
| E.5.2 | Secondary end point(s) |
| Proportion of patients with clinical benefit as assessed by the investigator. |
| Proportion de patients tirant un bénéfice clinique selon le médecin-investigateur evaluation. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Secondary endpoints will be evaluated during scheduled visits. |
| Les points d'évaluation secondaires seront évalués lors des visites planifiées. |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Roll-over study |
| étude de roll-over |
|
| 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 | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| étude de roll-over |
| Roll-over study |
|
| 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.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| 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 | No |
| 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 |
| Argentina |
| Australia |
| Austria |
| Belgium |
| Bulgaria |
| Canada |
| China |
| Czech Republic |
| Denmark |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Korea, Republic of |
| Netherlands |
| Norway |
| Poland |
| Russian Federation |
| Slovakia |
| Spain |
| Sweden |
| Thailand |
| Ukraine |
| United Kingdom |
| United States |
|
| 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
|
Patients will continue on study treatment until they are no longer
benefiting from study treatment or one of the discontinuation criteria is
met.
The study is expected to remain open for 5 years after the first
patient's first visit in this clinical study, or current treatment becomes
commercially available and reimbursed, or another access program
becomes available whichever comes first. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 21 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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