| Eligibility |
Inclusion 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 the following diagnosis: Advanced (inoperable, metastatic or locally advanced,
e.g. Stage IIIB, Stage IV) NSCLC (Non-Small Cell Lung Cancer) with confirmed BRAF
V600E/K activating mutation.
3. Patient is not eligible for any ongoing clinical trial in the same indication.
4. Is receiving care at a clinical site with a Treating Physician who has experience with
administering investigational agents for the end-stage NSCLC 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 ongoing clinical trials with dabrafenib
and/or trametinib 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 serum beta-human chorionic gonadotropin
(HCG) pregnancy test performed within 14 days prior to starting dabrafenib and
trametinib treatment. Patients with a positive pregnancy test result are not eligible
for the program. Patients 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 16 weeks following the last dose of treatment.
Contraceptive Methods for Females of Childbearing Potential:
Women of child-bearing 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: (for dabrafenib monotherapy or
combination therapy with trametinib)
- 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.
- Sterilization (at least 6 months prior to screening) for male partners. The
vasectomized male partner should be the sole partner for that subject.
- 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.
Notes:
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 child bearing potential.
If a patient becomes pregnant during the treatment period of the program, the
treatments should be stopped immediately.
12. Written patient informed consent must be obtained by the Treating Physician prior to
start of treatment in accordance with the applicable local regulatory requirements.
Medical exclusion criteria
Patients eligible for this Treatment Plan must not meet any of the following criteria:
1. Female who is pregnant or nursing (patient must discontinue nursing in order to enroll
in the program).
NOTE: Safety and efficacy in pregnant or nursing women has not been investigated.
Inclusion of pregnant or nursing woman may be considered in individually upon review
by the Novartis Country Pharma Organization Medical Advisor/Director.
2. Patients who have any lab abnormalities or AE/SAEs greater than Grade 3 (CTCAE v5.0).
3. Concurrent treatment with other systemic anti-cancer therapies is not allowed, with
the exception of whole brain radiation and brain radiosurgery. Patients who are
currently being treated with another systemic anti-cancer therapy (e.g., chemotherapy,
immune, biologic, or targeted therapy) must discontinue use prior to initiation of
treatment with trametinib and dabrafenib. NOTE: Radiation skin injury has been
reported with concurrent use of dabrafenib and radiation. All AEs/SAEs related to WBRT
(whole brain radiation) or brain radiosurgery are required to resolve to Grade 1 or
less (CTCAE 5.0) prior to start of the program treatment.
4. Patients who have received prior therapy with a BRAF inhibitor other than dabrafenib.
NOTE: Consideration may be given to those patients who have either (1) received prior
BRAF therapy and there is disease progression in the CNS only or (2) discontinued
prior BRAF therapy due to an adverse event that is not likely to recur in response to
treatment with Dabrafenib.
5. Presence of malignancy other than NSCLC 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. NOTE: Prospective RAS testing is not required. However, if the results of
previous RAS testing are known, they must be used in assessing eligibility.
6. Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to trametinib or dabrafenib, or excipients or to dimethyl sulfoxide
(DMSO).
7. Current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy.
8. Current evidence of cardiovascular risk including any of the following:
- LVEF<LLN
- A QT interval corrected for heart rate using the Bazett's formula = 480 msec;
- Clinically significant uncontrolled arrhythmias
- Acute coronary syndromes (including myocardial infarction and unstable angina).
- Congestive heart failure = Class II as defined by New York Heart Association
9. Known history for testing positive for Human Immunodeficiency Virus (HIV).
10. Not able to understand and to comply with treatment instructions and requirements.
11. History of hypersensitivity to any drugs or metabolites of similar chemical classes as
the product.
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