This clinical study is designed to provide continued access to pediatric patients who have previously participated in a dabrafenib and/or trametinib study and who in the opinion of the Investigator, would benefit from continued treatment
- Conditions
- Children and Adolescents with Cancers Harboring V600 mutationsMedDRA version: 20.0Level: LLTClassification code 10030935Term: Optic nerve gliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 25.1Level: LLTClassification code 10030953Term: Optic tract gliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10012773Term: Diencephalic gliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10027744Term: Mixed astrocytoma-oligodendrogliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.1Level: LLTClassification code 10030288Term: Oligodendroglioma malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10074669Term: Mixed gliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10075444Term: Malignant paragangliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10080666Term: Diffuse intrinsic pontine gliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 25.1Level: LLTClassification code 10087678Term: Diffuse midline glioma H3K27M mutationSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2018-004459-19-DK
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 250
Subjects eligible for inclusion in this study must meet all of the following criteria:
All subjects
1. Written informed consent, according to local guidelines, signed by the patients and / or by the parents or legal guardian prior to any study related screening procedures are performed.
2. Participation in a Novartis sponsored study such as TMT212X2101, DRB436G2201, DRB436A2102, regardless of current age
3. Parent study (or cohort of parent study) is planned to be closed
4. Patient has demonstrated treatment compliance, as assessed by the Investigator, within the parent study protocol requirement(s).
5. Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures.
For Subjects Entering the Treatment Period
6. Patient is currently receiving treatment with dabrafenib/trametinib monotherapy or combination within a Novartis Sponsored Drug Development study.
7. In the opinion of the Investigator, the subject is likely to benefit from continued treatment.
8. Does not require treatment with prohibited concomitant medications.
Are the trial subjects under 18? yes
Number of subjects for this age range: 250
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Patient has participated in a combination trial where dabrafenib and/or trametinib was dispensed in combination with another study medication. (Exception: Patients who were on the chemotherapy arm of the CDRB436G2201 study are eligible for this study after crossing over into the experimental treatment arm of the CDRB436G2201 study or have discontinued the study treatment and are now in follow-up)
2. Patient has permanently discontinued from study treatment in the parent protocol due to any reason.
3. Treatment with dabrafenib and/or trametinib for the patient’s indication is approved for marketing and the appropriate dosage form is commercially available and reimbursed in the local country
4. Patient currently has unresolved drug related severe toxicities for which dabrafenib and/or trametinib dosing has been interrupted in the parent study. If the patient should meet criteria to resume treatment on the parent protocol then they may be eligible for enrolment in this study.
5. Women of childbearing potential, defined as all females physiologically capable of becoming pregnant, must continue to use highly effective form of birth control method (contraception) during the study and for 16 weeks after stopping treatment with trametinib monotherapy or dabrafenib in combination with trametinib, and 2 weeks after stopping treatment with dabrafenib monotherapy, whichever is longer.
a. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (i.e. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
b. Female sterilization, surgically sterilized prior to the study (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 reproductive status of woman has been confirmed by follow-up hormone level assessment.
c. Sterilization (at least 6 months prior to screening) for male partners. The sterilized male partner should be the sole partner for that subject.
d. For subjects on dabrafenib monotherapy / trametinib in combination with dabrafenib: 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.
e. For subjects on trametinib monotherapy: Use of oral (estrogen and progesterone) injected or implanted combined hormonal methods of contraception, or placement of an intrauterine device (IUD), or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
Male subjects (including those that have had a vasectomy) not willing to use a condom during intercourse while taking trametinib and/or dabrafenib and not to father a child during the study and for the period of 16 weeks (for patients taking trametinib only, or in combination) or 2 weeks (for patients taking dabrafenib only) following stopping of study treatment.
6. Lactating females who are actively breast feeding.
7. Concurrent participation in other clinical trials using experimental therapies
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the long-term safety of treatment with dabrafenib, trametinib or the combination ;Secondary Objective: To assess the long-term effect of treatment with dabrafenib, trametinib or the combination on general health, growth and development<br><br>To assess efficacy as determined by institutional standard of care procedures;Primary end point(s): AEs, SAE, clinically significant changes in laboratory values and vital signs.;Timepoint(s) of evaluation of this end point: The study is intended to remain open for 7 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.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Serial measurements of height, weight, skeletal maturation, sexual maturation and cardiac function<br><br>Disease specific clinical benefit, as determined by investigator using institutional standard of care.;Timepoint(s) of evaluation of this end point: The study is intended to remain open for 7 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.