| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with BRAF V600 mutation positive |
| Pacientes con mutación BRAF V600 positiva |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with BRAF V600 mutation positive |
| Pacientes con mutación BRAF V600 positiva |
|
| 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 | 100000018545 |
|
| 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. |
| El objetivo principal es evaluar la seguridad a largo plazo, determinado por la aparición de AAs/AAGs |
|
| 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. |
| Evaluar el beneficio clínico, determinado por el investigador |
|
| 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 |
Los pacientes elegibles para inclusión en este estudio deberán cumplir todos los criterios siguientes:
1. Pacientes que estén recibiendo actualmente tratamiento con dabrafenib/trametinib en monoterapia o en combinación dentro de un estudio patrocinado por Novartis o anteriormente GSK, que hayan cumplido los requisitos para el objetivo principal.
2. A criterio del investigador deberían beneficiarse de la continuación del tratamiento.
3. Pacientes que hayan demostrado cumplimiento, evaluado por el investigador, dentro del(los) requisito(s) del protocolo del estudio principal.
4. Voluntad y capacidad para cumplir con las visitas programadas, planes de tratamiento y cualquier otro procedimiento del estudio.
5. Consentimiento informado por escrito obtenido antes de la inclusión en el estudio de continuación y de recibir la medicación del estudio. Si el consentimiento no puede ser expresado por escrito, deberá ser testificado y documentado formalmente, a ser posible a través de un testigo de confianza independiente.
6. Si el paciente es un menor, el padre/madre que firme el consentimiento para el menor deberá ser un padre/madre o tutor legalmente reconocido. Cuando el investigador y el padre/madre o tutor del(la) niño(a) lo consideren apropiado, el(la) niño(a) también participará en todas las discusiones sobre los ensayos y se obtendrá el asentimiento del menor si el(la) niño(a) tiene 7 años o más. |
|
| 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. |
Los pacientes elegibles para inclusión en este estudio no deberán cumplir ninguno de los criterios siguientes:
1. Pacientes a los que se les haya suspendido definitivamente el tratamiento del estudio en el protocolo principal por cualquier motivo.
2. La indicación del paciente está disponible comercialmente y es reembolsada en el país local.
3. El paciente ha participado en un ensayo de combinación en el que dabrafenib y/o trametinib se administró en combinación con otra medicación del estudio.
4. Paciente con toxicidades no resueltas actualmente por las que se le ha interrumpido la dosis de dabrafenib y/o trametinib en el estudio principal.
5. Pacientes embarazadas o en periodo de lactancia. Las mujeres lactantes deberán suspender la lactancia antes de la primera dosis del tratamiento del estudio y deben abstenerse de amamantar durante todo el periodo de tratamiento y durante 4 meses después de la última dosis del tratamiento del estudio.
6. No se permite tratamiento concomitante con otras terapias antineoplásicas sistémicas por ejemplo, quimioterapia, terapia inmunológica, biológica o dirigida), con la excepción de radioterapia.
7. Mujeres físicamente fértiles, definidas como todas las mujeres fisiológicamente capaces de quedarse embarazadas, a no ser que estén utilizando métodos anticonceptivos altamente eficaces durante la dosificación y durante 150 días después de suspender el tratamiento. Los métodos anticonceptivos altamente eficaces incluyen:
Abstinencia total (cuando esté en consonancia con el estilo de vida habitual y preferida de la paciente). La abstinencia periódica (por ejemplo, calendario, ovulación, métodos sintotérmicos, de postovulación) y el coitus interruptus no son métodos anticonceptivos aceptables.
Esterilización femenina (que se le haya realizado una ooforectomía bilateral con o sin histerectomía), histerectomía total o ligadura de trompas por lo menos seis semanas antes de tomar el tratamiento del estudio. En caso de ooforectomía solo, sólo cuando el estado reproductor de la mujer haya sido confirmado con evaluación de seguimiento del nivel hormonal.
Esterilización masculina (por lo menos 6 meses antes de la selección). La pareja varón vasectomizado debería ser la única pareja de dicha paciente.
Colocación de un dispositivo intrauterino (DIU) o sistema intrauterino (SIU) no hormonal con una tasa de fallo documentada de menos de un 1% por año.
Anticonceptivo de doble barrera: preservativo o capuchón oclusivo (diafragma o capuchón en bóveda/cervical) con un agente espermicida vaginal (gel/espuma/crema espermicida/supositorio vaginal).
Nota: los métodos basados en hormonas (por ejemplo, anticonceptivos hormonales) no se consideran métodos anticonceptivos altamente eficaces debido a las posibles interacciones fármaco-fármaco con dabrafenib.
8. Varones sexualmente activos, a menos que utilicen un preservativo durante el coito mientras reciban tratamiento y durante 150 días después de suspender el tratamiento y no deberían engendrar hijos durante este periodo. Los varones vasectomizados también deberán utilizar un preservativo durante el coito para evitar la liberación del fármaco vía fluido seminal.
9. Las mujeres se considerarán postmenopáusicas y físicamente no fértiles si presentan amenorrea natural (espontánea) durante 12 meses con un perfil clínico apropiado (por ejemplo, edad apropiada, historial de síntomas vasomotores) o han sido sometidas a ooforectomía bilateral quirúrgica (con o sin histerectomía), histerectomía total o a ligadura de trompas por lo menos seis semanas antes. En el caso de ooforectomía sola, sólo cuando el estado reproductor de la mujer haya sido confirmado con evaluación de seguimiento del nivel hormonal será considerada físicamente no fértil. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Frequency and severity of AEs/SAEs |
| Frecuencia y severidad de los AAs/AAGs |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Endpoints will be evaluated throughout the study. |
| Las variables serán evaluadas durtante todo el transcurso del estudio. |
|
| E.5.2 | Secondary end point(s) |
| Proportion of patients with clinical benefit as assessed by the investigator at scheduled visits. |
| Proporción de pacientes con beneficio clínico, determinado por el investigador en las visitas programadas |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Endpoints will be evaluated throughout the study. |
| Las variables serán evaluadas durtante todo el transcurso del estudio. |
|
| 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 |
| Estudio de continuación |
|
| 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 | 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 |
| Estudio de continuación |
| 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
| 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 | 3 |
| 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 |
| Canada |
| China |
| Denmark |
| France |
| Germany |
| Italy |
| Korea, Republic of |
| Netherlands |
| Norway |
| Poland |
| 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
|
The end of the study will occur after all patients in the study have completed their last assessment per protocol (llow-up visit that occurs 30 days after the patient’s last dose or until SAE follow up is resolved). Patients may continue until :
End of treatment visit
One of the premature patient withdrawal criteria is met
5 years after the first patient’s first visit
A local access program becomes available
Current treatment becomes commercially available and reimbursed |
| El final del estudio ocurrirá después del UVUP. La última evaluación para cada paciente es la visita de seguimiento a realizar 30 días después de la última dosis del tratamiento del estudio administrada al paciente o hasta la resolución de los seguimientos requeridos de AAG, lo que ocurra más tarde. Los pacientes puede continuar con el tratamiento del estudio hasta que se cumplan uno de los siguientes criterios, lo que ocurra primero: refierase al apartado 4.3 del protocol. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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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