The purpose of this Cohort Treatment Plan is to allow access to trametinib (monotherapy or in combination) and dabrafenib (monotherapy or in combination) for eligible patients diagnosed with metastatic melanoma BRAF mutation-positive.
The patient's Treating Physician should follow the suggested treatment guidelines and comply with all local health authority regulations. The requesting Treating Physician submitted a request for access to drug (often referred to as Compassionate Use) to Novartis which was reviewed and approved by the medical team experienced with the drug and indication. This program will provide access to patients until: - All participating countries have received marketing authorization and product is commercially available and accessible to all participating patient(s) or - Alternative treatment options are available and/or - In case of changes in the safety profile or a lack of overall efficacy of the product.
Drug: Dabrafenib and Trametinib
The starting dose of the combination treatment will be administered as follows:
Dabrafenib, 150 mg, twice daily (BID);
Trametinib, 2.0 mg, once daily (QD)
If administration of dabrafenib is interrupted or permanently discontinued, administration of trametinib may continue.
If administration of trametinib is interrupted or permanently discontinued, administration of dabrafenib may be continued.
Patients eligible for inclusion in this Treatment Plan have to meet all of the following
criteria: 1. Has or is willing to give consent to the Treating Physician in accordance with the local regulatory requirements, with age at the time of consent ≥18 years. 2. Has confirmed BRAF V600 or other BRAF activating mutation-positive metastatic melanoma. Histologically Stage IIIC (unresectable) or Stage IV (metastatic) cutaneous melanoma with confirmed BRAF V600E/K positive mutation. 3. All clinical trials that the patient might qualify for have been ruled out. 4. Is receiving care at a clinical site with a Treating Physician who has experience with administering investigational agents for the end-stage melanoma population, or the patient is willing and/or able to travel to a site and receive treatment under the guidance of physician with this experience. NOTE: The latter option would require the patient being evaluated in advance by the Treating Physician at the experienced site and his/her agreement to assume responsibility for the care of the patient. 5. Is able to retain oral medication and swallow tablets/capsules (appropriate exceptions allowed for patients who are unable to swallow tablets/capsules - this is subject to availability of alternative (liquid) oral formulations). 6. Does not require treatment with any (other) anti-cancer medication (exceptions might be allowed and are subject to individual evaluation). 7. For patients with active brain metastases: the patient does not require or is ineligible for immediate local treatment. 8. Is not eligible for participation in any of the IMP's ongoing clinical trials or has recently completed a clinical trial that has been terminated and, after considering other options (e.g., trial extensions, amendments, etc.), the clinical team has determined that treatment is necessary and there are no other feasible alternatives for the patient. 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 3 (or equivalent) and is in stable clinical condition. NOTE: patient in rapidly deteriorating clinical condition prior to start of therapy should not be considered for this program.
10. Does not require treatment with prohibited concomitant medications
11. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (HCG) pregnancy test performed within 14 days prior to starting dabrafenib and trametinib treatment. Subjects with a positive pregnancy test result must be excluded from the program. Subjects with a negative pregnancy test result must agree to use an effective contraception method as described below throughout the treatment period and for a total of 4 months following the last dose of treatment.
Contraceptive Methods for Females of Childbearing Potential: - An intrauterine device with a documented failure rate of less than 1% per year - Vasectomized partner who is sterile prior to the female patient's entry into the Compassionate Use program, and this male is the sole sexual partner for that female. - Complete abstinence from sexual intercourse for 14 days prior to first dose of treatment, through the dosing period, and for at least 4 months after the last dose of treatment. Abstinence is only acceptable when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception. - Double-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with vaginal spermicidal agent (foam/gel/cream/suppository).
Note: Hormonal-based methods (e.g., oral contraceptives) are not permitted as contraception
due to potential drug-drug interactions with dabrafenib.
Females Not of Childbearing Potential Non-childbearing potential (i.e., physiologically
incapable of becoming pregnant) is defined as any female who has had a documented
hysterectomy, bilateral oophorectomy (ovariectomy), bilateral tubal ligation or tubal
occlusion, or is post-menopausal.
A practical definition accepts menopause after 1 year without menses with an appropriate
clinical profile; e.g., age appropriate, >45 years in the absence of hormone replacement
therapy (HRT). In questionable cases, the patient must have a follicle stimulating hormone
(FSH) value >40 mIU/mL and an estradiol value