Pediatric Long-Term Follow-up and Rollover Study

NCT03975829 | Active Not Recruiting Phase 4 FDA Drug

• 2 other identifiers: CDRB436G24012023-509276-42-00
• Study Type: interventional
• Target: 165
• Locations: 19 countries
• Sites: 55

Brief Summary

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

Conditions

Glioblastoma; Extraventricular Neurocytoma; Cerebellar Liponeurocytoma; Neurofibromatosis Type 1; Anaplastic Pleomorphic Xanthoastrocytoma; Diffuse Astrocytoma; Anaplastic Astrocytoma; Desmoplastic Infantile Astrocytoma and Ganglioglioma; Papillary Glioneuronal Tumor; Rosette-forming Glioneuronal Tumor; Oligodendroglioma, Childhood; Pilocytic Astrocytoma; Giant Cell Astrocytoma; Astrocytoma; Anaplastic Oligodendroglioma; Pleomorphic Xanthoastrocytoma; Angiocentric Glioma; Chordoid Glioma of Third Ventricle; Gangliocytoma; Ganglioglioma; Anaplastic Ganglioglioma; Dysplastic Gangliocytoma of Cerebrellum; Central Neurocytoma

Keywords

v600-mutation; neuroblastoma; Trametinib; pediatrics; Langerhans Cell Histiocytosis; low grade glioma; plexiform neurofibromas; high grade glioma; dabrafenib; NF-1

Outcome Measures

Primary Outcomes (1)

• Number of participants with Adverse Events and Serious Adverse Events (SAEs)

  To assess the long-term safety of treatment with dabrafenib, trametinib or the combination.

  Baseline up to approximately 7 years

Secondary Outcomes (6)

• Percentage of participants with height (measured by cm or in) changes over time

  Baseline up to approximately 7 years

• Percentage of participants with weight (measured by kg or lb) changes over time

  Baseline up to approximately 7 years

• Percentage of participants with skeletal maturation (measured by bone age on x-ray or MRI) changes over time

  Baseline up to approximately 7 years

• Percentage of participants with sexual maturation (measured by tanner staging criteria) changes over time

  Baseline up to approximately 7 years

• Percentage of participants with cardiac function (measured by ECG) changes over time

  Baseline up to approximately 7 years

Study Arms (1)

Dabrafenib and/or trametinib

EXPERIMENTAL

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; Drug: trametinib

Interventions

trametinib DRUG

trametinib oral, once daily

Also known as: TMT212

Dabrafenib and/or trametinib

dabrafenib DRUG

dabrafenib oral, twice daily

Also known as: DRB436

Dabrafenib and/or trametinib

Eligibility Criteria

• Age: 1 Year - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (55)

Phoenix Children s Hospital

Phoenix, Arizona, 85016, United States

Location

Childrens National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Nicklaus Childrens Hospital

Miami, Florida, 33155, United States

Location

Indiana Uni School of Medicine

Indianapolis, Indiana, 46202-2810, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Ctr

New York, New York, 10065, United States

Location

Cinn Children Hosp Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

St Jude Childrens Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Childrens Hospital

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1428AQK, Argentina

Location

Novartis Investigative Site

Darlinghurst, New South Wales, 2010, Australia

Location

Novartis Investigative Site

Parkville, Victoria, 3052, Australia

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Barretos, São Paulo, 14784 400, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 04829-310, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 08270-070, Brazil

Location

Novartis Investigative Site

Vancouver, British Columbia, V6H 3V4, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1X8, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1C5, Canada

Location

Novartis Investigative Site

Brno, 625 00, Czechia

Location

Novartis Investigative Site

Prague, 150 06, Czechia

Location

Novartis Investigative Site

Copenhagen, DK-2100, Denmark

Location

Novartis Investigative Site

Tampere, 33521, Finland

Location

Novartis Investigative Site

Rennes, Brittany Region, 35203, France

Location

Novartis Investigative Site

Brest, 29609, France

Location

Novartis Investigative Site

Marseille, 13885, France

Location

Novartis Investigative Site

Paris, 75231, France

Location

Novartis Investigative Site

Rennes, 35033, France

Location

Novartis Investigative Site

Vandœuvre-lès-Nancy, 54511, France

Location

Novartis Investigative Site

Villejuif, 94800, France

Location

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Novartis Investigative Site

Augsburg, 86179, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Petah Tikva, 4920235, Israel

Location

Novartis Investigative Site

Florence, FI, 50139, Italy

Location

Novartis Investigative Site

Genova, GE, 16147, Italy

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Roma, RM, 00165, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Setagaya-ku, Tokyo, 1578535, Japan

Location

Novartis Investigative Site

Osaka, 5340021, Japan

Location

Novartis Investigative Site

Utrecht, 3584 CS, Netherlands

Location

Novartis Investigative Site

Moscow, 117198, Russia

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Valencia, 46026, Spain

Location

Novartis Investigative Site

Stockholm, 17176, Sweden

Location

Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Novartis Investigative Site

Liverpool, L12 2AP, United Kingdom

Location

Novartis Investigative Site

London, NW1 2BU, United Kingdom

Location

Novartis Investigative Site

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Glioblastoma; Ganglioneuroma; Ganglioglioma; Neurocytoma; Neurofibromatosis 1; Neuroblastoma; Histiocytosis, Langerhans-Cell; Neurofibroma, Plexiform; Glioma

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Peripheral Nervous System Neoplasms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2019
• First Posted: June 5, 2019
• Study Start: November 4, 2019
• Primary Completion (Estimated): November 5, 2026
• Study Completion (Estimated): November 5, 2026
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

CA (3); GB (4); JP (2); US (12); RU (1); AU (2); DE (5); AR (1); FR (7); NL (1); SE (1); ES (2); IL (1); CZ (2); BR (3); FI (1); IT (5); BE (1); DK (1)