| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with BRAF V600 mutation positive |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with BRAF V600 mutation positive |
|
| 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 | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10029104 |
| E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
| 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 long term safety as assessed by the occurrence of AEs/SAEs. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective of the study is to evaluate clinical benefit as assessed by the Investigator. |
|
| 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 and/or 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. Does not require treatment with prohibited concomitant medications |
|
| E.4 | Principal exclusion criteria |
Subjects eligible for this study must not meet any of the following criteria:
1. Subject has been previously permanently discontinued from study treatment in the parent protocol due to any reason.
2. Subject’s indication is commercially available and reimbursed in the local country.
3. Subject currently has unresolved toxicities for which dabrafenib and/or trametinib dosing has been interrupted in the parent study.
4. Pregnant or nursing (lactating) women 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.
5. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during dosing and for 16 weeks after stopping treatment with trametinib (for trametinib monotherapy trials); 2 weeks after stopping treatment with dabrafenib (for dabrafenib monotherapy trials); 16 weeks after stopping treatment with trametinib or 2 weeks after stopping treatment with dabrafenib whichever is longer (for trials of dabrafenib in combination with trametinib).
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 taking study drug). The vasectomized male partner should be the sole partner for that subject.
• Dabrafenib monotherapy or in combination with trametinib: Placement of a hormonal or non-hormonal intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year.
Trametinib monotherapy only: Use of oral (estrogen and progesterone), injected or implanted combined hormonal methods of contraception or placement of an IUD or IUS, or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
Note(s):
• Double-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/cream/suppository) are not considered highly effective methods of contraception.
• Hormonal-based methods (e.g., oral contraceptives) are not considered as highly effective methods of contraception due to potential drug-drug interactions with dabrafenib
• 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 childbearing potential.
6. Sexually active males (including those that have had a vasectomy) taking the dabrafenib and/or trametinib therapy must use a condom during intercourse, and should not father a child during this period. The minimum amount of time a subject must use a condom after last treatment is as follows:
• 16 weeks post treatment discontinuation dabrafenib in combination with trametinib
• 2 weeks after treatment with dabrafenib monotherapy
• 16 weeks after treatment with trametinib monotherapy |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Frequency and severity of AEs/SAEs |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Primary endpoints will be evaluated throughout the study. |
|
| E.5.2 | Secondary end point(s) |
| Proportion of subjects with clinical benefit as assessed by the investigator at scheduled visits |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Secondary endpoints will be evaluated during scheduled visits. |
|
| 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 | Yes |
| 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 |
|
| 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 |
|
| 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 | 21 |
| 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 |
| China |
| Japan |
| Thailand |
| United States |
| Austria |
| Denmark |
| France |
| Germany |
| Hungary |
| Netherlands |
| Spain |
|
| 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 10 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, or study treatment becomes available through other programs per local laws and regulations, whichever comes first. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 29 |
| E.8.9.2 | In all countries concerned by the trial years | 10 |
| 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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