Compassionate Use of trametinib in low grade glioma
Study ID: STU 122016-043
Trametinib suspension given by mouth once daily. Starting dose of 0.025 mg/kg/day. Maximum dose is the adult dose of 2 mg daily. Dosing can be decreased by 50% should toxicity occur. Patient will be monitored with monthly physical examinations, laboratory evaluations, eKGs, dermatological examinations and ophthalmologic evaluations. Therapy will continue if the tumor responses and side effects are minimal.
Patients eligible for inclusion in this Treatment Plan have to meet all of the following criteria: 1. Provides signed and dated informed consent, with age at the time of consent >=18 years. NOTE: Safety and efficacy in the paediatric population has not been investigated. Inclusion of patients who are <18 years of age will be considered on a case-by-case basis upon review by the Novartis Medical Advisor. 2. Has confirmed BRAF V600 or other BRAF activating mutation-positive metastatic melanoma (or other appropriate indication for which there is evidence of efficacy). Histologically Stage IIIC (unresectable) or Stage IV(metastatic) cutaneous melanoma with confirmed BRAF V600E/K positive mutation. Note: patients with other activating BRAF mutations will require central team review to determine eligibility. 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 swallow and retain oral medication (appropriate exceptions allowed). 6. Does not require treatment with any anti-cancer medication (except for whole brain radiation or brain radiosurgery) while on the Individual Patient Program. 7. Has not participated in the following GSK sponsored clinical trial (Combi-V: MEK116513, Combi-D: MEK115306, Combi-AD: BRF115532) for melanoma indication prior to program participation. 8. For patients with active brain metastases: the patient does not require or is ineligible for immediate local treatment. 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 (see Appendix 1 Section 14.1 of the Treatment Plan). 11. Does not have any medical conditions or physical examination or clinical laboratory findings which, in the opinion of the Novartis Country Pharma Organization Medical Advisor/Director, would put the patient at high risk for an adverse outcome. 12. Has no malignancy other than melanoma within 1 year of enrolment into this program or any malignancy with confirmed activating RAS mutation. (Patient with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma is eligible.) 13. For patients receiving prior BRAF-inhibitor or MEK-inhibitor treatment, when the patient[Single Quote]s tumor has not progressed, based on radiographic and clinical assessments, such patients may receive therapy with: a) trametinib in combination with dabrafenib (in case of an adverse event related to a previous BRAF or MEK inhibitor other than trametinib or dabrafenib or according to the Treating Physician[Single Quote]s judgement). Prior treatment (except trametinib and dabrafenib) should have been stopped for a period of 5 half lives or 28 days (whichever is longer) before starting treatment of this study. b) trametinib monotherapy if the patient has benefited from a treatment with a BRAF-inhibitor without progression but cannot receive it anymore due to tolerability reason. 14. For patients receiving prior BRAF-i or MEK-i Tx, when the patient[Single Quote]s tumor has progressed based on radiographic and clinical assessments, such patients may receive therapy with trametinib in combination with dabrafenib when: a) The disease progression occurred after a period of at least 6 months of clinical benefit (Response or Stable Disease) on monotherapy and the progression is characterized by a limited radiographic progression in the absence of clinical signs and symptoms of progression. b) There were no treatment-related grade 4 AEs or any SAEs during the last 4 weeks of treatment. 15. If a female subject is of childbearing potential, she must have a serum β-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 study. 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: o An intrauterine device with a documented failure rate of less than 1% per year o Vasectomized partner who is sterile prior to the female patient[Single Quote]s entry into the Compassionate Use program, and this male is the sole sexual partner for that female. o 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. o 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 <40 pg/mL (<140 pmol/L). Female patients determined not to be post-menopausal must use adequate contraception, as defined immediately above for females of childbearing potential. Female subjects 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. If a subject becomes pregnant during the treatment period of the study, the treatments should be stopped immediately.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Laura Jean Klesse
NOVARTIS PHARMACEUTICALS CORPORATION
Brain and Nervous System