Pediatric Long-Term Follow-up and Rollover Study

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03975829

Collaborator

(none)

250

Enrollment

Locations

Arm

80.5

Anticipated Duration (Months)

13.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A roll-over study to assess long-term effect in pediatric patients treated with dabrafenib and/or trametinib.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Astrocytoma Anaplastic Astrocytoma Astrocytoma Oligodendroglioma, Childhood Anaplastic Oligodendroglioma Glioblastoma Pilocytic Astrocytoma Giant Cell Astrocytoma Pleomorphic Xanthoastrocytoma Anaplastic Pleomorphic Xanthoastrocytoma Angiocentric Glioma Chordoid Glioma of Third Ventricle Gangliocytoma Ganglioglioma Anaplastic Ganglioglioma Dysplastic Gangliocytoma of Cerebrellum Desmoplastic Infantile Astrocytoma and Ganglioglioma Papillary Glioneuronal Tumor Rosette-forming Glioneurona Tumor Central Neurocytoma Extraventricular Neurocytoma Cerebellar Liponeurocytoma Neurofibromatosis Type 1	Drug: dabrafenib Drug: trametinib	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open Label, Multi-center Roll-over Study to Assess Long-term Effect in Pediatric Patients Treated With Tafinlar (Dabrafenib) and/or Mekinist (Trametinib)

Actual Study Start Date :

Nov 4, 2019

Anticipated Primary Completion Date :

May 29, 2026

Anticipated Study Completion Date :

Jul 20, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dabrafenib and/or trametinib Patients in this study may receive one of the following treatments received in the parent study which are: Patients who received monotherapy of either of dabrafenib or trametinib Patients who received combination of dabrafenib and trametinib Patients who discontinued treatment on parent study are still offered to participate in long-term follow-up	Drug: dabrafenib dabrafenib oral, twice daily Other Names: DRB436 Drug: trametinib trametinib oral, once daily Other Names: TMT212

Arm

Intervention/Treatment

Experimental: Dabrafenib and/or trametinib

Patients in this study may receive one of the following treatments received in the parent study which are: Patients who received monotherapy of either of dabrafenib or trametinib Patients who received combination of dabrafenib and trametinib Patients who discontinued treatment on parent study are still offered to participate in long-term follow-up

Drug: dabrafenib

dabrafenib oral, twice daily

Other Names:

DRB436

Drug: trametinib

trametinib oral, once daily

Other Names:

TMT212

Outcome Measures

Primary Outcome Measures

Number of participants with Adverse Events and Serious Adverse Events (SAEs) [Baseline up to approximately 7 years]
To assess the long-term safety of treatment with dabrafenib, trametinib or the combination.

Secondary Outcome Measures

Percentage of participants with height (measured by cm or in) changes over time [Baseline up to approximately 7 years]
Developmental monitoring: Serial measurements of height will be collected throughout the study
Percentage of participants with weight (measured by kg or lb) changes over time [Baseline up to approximately 7 years]
Developmental monitoring: Serial measurements of weight will be collected throughout the study
Percentage of participants with skeletal maturation (measured by bone age on x-ray or MRI) changes over time [Baseline up to approximately 7 years]
Developmental monitoring: Serial measurements of skeletal maturation will be collected throughout the study
Percentage of participants with sexual maturation (measured by tanner staging criteria) changes over time [Baseline up to approximately 7 years]
Developmental monitoring: Serial measurements of sexual maturation will be collected throughout the study
Percentage of participants with cardiac function (measured by ECG) changes over time [Baseline up to approximately 7 years]
Developmental monitoring: Serial measurements of cardiac function will be collected throughout the study
Clinical Benefit (measured by CT/MRI) [Baseline up to approximately 7 years]
Disease specific clinical benefit, as determined by investigator using institutional standard of care. Investigator will measure tumor response based on the Response Assessment used for the subject in the parent protocol (Response Assessment in Neuro-Oncology (RANO) criteria for solid tumors, RECIST, NF1 Volumetric, Neuroblastoma, or LCH criteria).

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

All Subjects:

Written informed consent, according to local guidelines, signed by the subjects and/or by the parents or legal guardian prior to any study related screening procedures are performed.
Participation in a Novartis sponsored study such as CTMT212X2101, CDRB436G2201, CDRB436A2102, regardless of current age.
Parent study (or cohort of parent study) is planned to be closed.
Subject has demonstrated compliance, as assessed by the investigator, within the parent study protocol requirement(s).
Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures.

For Subjects Entering the Treatment Period:

Subject is currently receiving treatment with dabrafenib/trametinib monotherapy or combination within a Novartis Sponsored Drug Development study. Note that subjects who were on the chemotherapy arm of the CDRB436G2201 study are eligible for treatment period of this study only after crossing over into the experimental treatment arm of the CDRB436G2201 study
In the opinion of the investigator is likely to benefit from continued treatment.

Key Exclusion Criteria:

All Subjects:

Subject has participated in a combination trial where dabrafenib and/or trametinib was dispensed in combination with another study medication.

For Subjects Entering the Treatment Period:

Subject has permanently discontinued from study treatment in the parent protocol due to any reason.
Treatment with dabrafenib and/or trametinib for the subject's indication is approved for marketing and the appropriate dosage form is commercially available and reimbursed in the local country
Subject currently has unresolved drug related severe toxicities for which dabrafenib and/or trametinib dosing has been interrupted in the parent study. If the subject should meet criteria to resume treatment on the parent protocol then they may be eligible for treatment in this study.

Other protocol-defined inclusion/exclusion may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
2	Childrens National Hospital CQTI571A2306	Washington	District of Columbia	United States	20010
3	Johns Hopkins University IDS Pharmacy	Baltimore	Maryland	United States	21287
4	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	University of Minnesota	Minneapolis	Minnesota	United States	55455
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Cincinnati Children s Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
8	St Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
9	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 1X8
10	Novartis Investigative Site	Rennes	Bretagne	France	35203
11	Novartis Investigative Site	Brest Cedex	Finistere	France	29609
12	Novartis Investigative Site	Marseille Cedex 05		France	13885
13	Novartis Investigative Site	Paris		France	75231
14	Novartis Investigative Site	Vandoeuvre Les Nancy		France	54511
15	Novartis Investigative Site	Villejuif Cedex		France	94800
16	Novartis Investigative Site	Madrid		Spain	28009
17	Novartis Investigative Site	Sutton	Surrey	United Kingdom	SM2 5PT
18	Novartis Investigative Site	London		United Kingdom	WC1N 3JH