Phase II Pediatric Study With Dabrafenib in Combination With Trametinib in Patients With HGG and LGG

Phase II Open-label Global Study to Evaluate the Effect of Dabrafenib in Combination With Trametinib in Children and Adolescent Patients With BRAF V600 Mutation Positive Low Grade Glioma (LGG) or Relapsed or Refractory High Grade Glioma (HGG)

Sponsors

Lead Sponsor: Novartis Pharmaceuticals

Source Novartis
Brief Summary

The purpose of this study is to investigate the activity of dabrafenib in combination with trametinib in children and adolescent patients with BRAF V600 mutation positive low grade glioma or relapsed or refractory high grade glioma.

Overall Status Recruiting
Start Date December 28, 2017
Completion Date October 16, 2025
Primary Completion Date August 23, 2021
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
HGG cohort: Overall response rate (ORR) Within the first 32 weeks of treatment
LGG cohort: Overall response rate (ORR) Within the first 32 weeks of treatment
Secondary Outcome
Measure Time Frame
HGG cohort: Overall response rate (ORR) Within the first 32 weeks of treatment
HGG and LGG cohorts: Duration of response (DOR) Within the first year of treatment
HGG and LGG cohorts: Time to response (TTR) Within the first year of treatment
HGG and LGG cohorts: Overall survival (OS) 2 years from last patient dosed
HGG and LGG cohorts: Progression free survival (PFS) Within 4 months of treatment
Patients on DRB+TMT: Area under the curve (AUClast) Within the first month of treatment
Patients on DRB+TMT: Area under the curve (AUCtau) Within the first month of treatment
Patients on DRB+TMT: Maximum Plasma Concentration (Cmax) Within the first month of treatment
Patients on DRB+TMT: Time to reach maximum concentration (Tmax) Within the first month of treatment
Patients on DRB+TMT: Elimination half-life (T1/2) Within the first month of treatment
Patients on DRB+TMT: Predose plasma concentration (Ctrough) Within the first month of treatment
HGG and LGG cohorts: Adverse events From first dose to end of treatment (EOT)
HGG and LGG cohorts: Vital signs First dose to end of treatment
HGG and LGG cohorts: Abnormal lab values First dose to end of treatment
HGG and LGG cohorts: Changes in Electrocardiogram (ECG) First dose to end of treatment
HGG and LGG cohorts: ECHO First dose to end of treatment
LGG cohort: Overall response rate (ORR) Within the first 32 weeks of treatment
HGG and LGG cohort: Palatability of pediatric formulations Within the first 5 weeks of treatment
LGG cohort: PROMIS Parent Proxy scale Within the first 32 weeks of treatment
HGG and LGG Cohorts: Clinical benefit rate (CBR) Within the first 24 weeks of treatment
LGG cohort: 2 year Overall survival (OS) 2 years from first dose
Enrollment 142
Condition
Intervention

Intervention Type: Drug

Intervention Name: dabrafenib

Description: dabrafenib oral, twice daily.

Other Name: DRB436

Intervention Type: Drug

Intervention Name: trametinib

Description: trametinib oral, once daily.

Other Name: TMT212

Intervention Type: Drug

Intervention Name: Carboplatin with vincristine

Description: Chemotherapy of carboplatin with vincristine - LGG only

Arm Group Label: LGG cohort: Carboplatin with vincristine

Eligibility

Criteria:

Inclusion Criteria: - Diagnosis of BRAF V600 mutant High Grade glioma that has relapsed, progressed or failed to respond to frontline therapy - Diagnosis of BRAF V600 mutant Low Grade glioma with progressive disease following surgical excision, or non-surgical candidates with necessity to begin first systemic treatment because of a risk of neurological impairment with progression. - Confirmed measurable disease Exclusion Criteria: - Previous treatment with dabrafenib, trametinib, other RAF inhibitor, other MEK or ERK inhibitor - HGG patient: Cancer treatment within the past 3 weeks. LGG patient: Any systemic therapy or radiotherapy prior to enrollment - LGG patients: history of allergic reaction or contraindications to the use of carboplatin or vincristine - Stem cell transplant within the past 3 months - History of heart disease - Pregnant or lactating females Other protocol-defined Inclusion/exclusion may apply.

Gender: All

Minimum Age: 12 Months

Maximum Age: 17 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals
Overall Contact

Last Name: Novartis Pharmaceuticals

Phone: 1-888-669-6682

Email: [email protected]

Location
Facility: Status:
Phoenix Childrens Hospital | Phoenix, Arizona, 85016, United States Withdrawn
Children's Hospital of Orange County | Orange, California, 92868, United States Recruiting Laura Gates 714-509-4348 [email protected] Chenue Abongwa Principal Investigator
Childrens Hospital Colorado | Aurora, Colorado, 80045, United States Withdrawn
Children s National Hospital | Washington, District of Columbia, 20010, United States Active, not recruiting
Nemours Children's Clinic Division of Endocrinology | Jacksonville, Florida, 32207, United States Withdrawn
Nicklaus Children s Hospital | Miami, Florida, 33155, United States Active, not recruiting
Ann and Robert H Lurie Childrens Hospital of Chicago | Chicago, Illinois, 60611, United States Active, not recruiting
Indiana University School of Medicine | Indianapolis, Indiana, 46202-2810, United States Active, not recruiting
Johns Hopkins University IDS Pharmacy John Hopkins Hospital | Baltimore, Maryland, 21287, United States Active, not recruiting
Dana Farber Cancer Institute | Boston, Massachusetts, 02215, United States Withdrawn
Children s Mercy Hospital | Kansas City, Missouri, 64108, United States Withdrawn
Washington University School of Medicine SC | Saint Louis, Missouri, 63110, United States Completed
Memorial Sloan Kettering Cancer Center PC-2 | New York, New York, 10065, United States Withdrawn
Cincinnati Children's Hospital Medical Center Cancer & Blood Disease Inst. | Cincinnati, Ohio, 45229-3039, United States Active, not recruiting
Children's Hospital of Pittsburgh of UPMC | Pittsburgh, Pennsylvania, 15224, United States Withdrawn
St Jude Children's Research Hospital | Memphis, Tennessee, 38105, United States Completed
UT Southwestern Medical Center UTSW/Children's Medical Center | Dallas, Texas, 75235, United States Withdrawn
Texas Children s Hospital Baylor College of Medicine | Houston, Texas, 77030, United States Active, not recruiting
Novartis Investigative Site | Caba, Buenos Aires, C1428AQK, Argentina Active, not recruiting
Novartis Investigative Site | Randwick, New South Wales, 2130, Australia Active, not recruiting
Novartis Investigative Site | Parkville, Victoria, 3052, Australia Active, not recruiting
Novartis Investigative Site | Brussels, BE-B-1200, Belgium Active, not recruiting
Novartis Investigative Site | Leuven, 3000, Belgium Withdrawn
Novartis Investigative Site | Barretos, SP, 14784 400, Brazil Active, not recruiting
Novartis Investigative Site | Sao Paulo, SP, 08270-070, Brazil Active, not recruiting
Novartis Investigative Site | Sao Paulo, SP, Brazil Active, not recruiting
Novartis Investigative Site | Vancouver, British Colombia, V6H 3V4, Canada Recruiting
Novartis Investigative Site | Toronto, Ontario, M5G 1X8, Canada Recruiting
Novartis Investigative Site | Montreal, Quebec, H3T 1C5, Canada Recruiting
Novartis Investigative Site | Montreal, Quebec, H4A 3J1, Canada Recruiting
Novartis Investigative Site | Brno, 613 00, Czechia Active, not recruiting
Novartis Investigative Site | Praha 5, 150 06, Czechia Active, not recruiting
Novartis Investigative Site | Copenhagen, 2100 O, Denmark Active, not recruiting
Novartis Investigative Site | Tampere, 33521, Finland Active, not recruiting
Novartis Investigative Site | France, Villejuif, 94800, France Active, not recruiting
Novartis Investigative Site | Angers Cedex 1, 49033, France Withdrawn
Novartis Investigative Site | Lille Cedex, 59020, France Completed
Novartis Investigative Site | Lyon Cedex, 69373, France Active, not recruiting
Novartis Investigative Site | Marseille Cedex 5, 13385, France Withdrawn
Novartis Investigative Site | Paris, 75231, France Active, not recruiting
Novartis Investigative Site | Strasbourg Cedex, F 67098, France Active, not recruiting
Novartis Investigative Site | Toulouse Cedex 9, 31059, France Active, not recruiting
Novartis Investigative Site | Augsburg, 86179, Germany Active, not recruiting
Novartis Investigative Site | Berlin, 13353, Germany Active, not recruiting
Novartis Investigative Site | Essen, 45147, Germany Active, not recruiting
Novartis Investigative Site | Gottingen, 37075, Germany Active, not recruiting
Novartis Investigative Site | Hamburg, 20246, Germany Active, not recruiting
Novartis Investigative Site | Heidelberg, 69120, Germany Active, not recruiting
Novartis Investigative Site | Koeln, 50937, Germany Active, not recruiting
Novartis Investigative Site | Petach-Tikva, 49202, Israel Active, not recruiting
Novartis Investigative Site | Tel-Hashomer, 52621, Israel Completed
Novartis Investigative Site | Firenze, FI, 50139, Italy Active, not recruiting
Novartis Investigative Site | Genova, GE, 16147, Italy Active, not recruiting
Novartis Investigative Site | Milano, MI, 20133, Italy Active, not recruiting
Novartis Investigative Site | Roma, RM, 00165, Italy Active, not recruiting
Novartis Investigative Site | Torino, TO, 10126, Italy Active, not recruiting
Novartis Investigative Site | Fukuoka city, Fukuoka, 812-8582, Japan Completed
Novartis Investigative Site | Setagaya-ku, Tokyo, 157-8535, Japan Active, not recruiting
Novartis Investigative Site | Osaka, 534-0021, Japan Active, not recruiting
Novartis Investigative Site | Utrecht, CS, 3584, Netherlands Active, not recruiting
Novartis Investigative Site | Rotterdam, 3015 CE, Netherlands Withdrawn
Novartis Investigative Site | Moscow, 117198, Russian Federation Active, not recruiting
Novartis Investigative Site | Cordoba, Andalucia, 14004, Spain Withdrawn
Novartis Investigative Site | Barcelona, Catalunya, 08035, Spain Active, not recruiting
Novartis Investigative Site | Madrid, 28007, Spain Active, not recruiting
Novartis Investigative Site | Madrid, 28009, Spain Active, not recruiting
Novartis Investigative Site | Valencia, 46026, Spain Active, not recruiting
Novartis Investigative Site | Stockholm, 17176, Sweden Active, not recruiting
Novartis Investigative Site | Zuerich, 8032, Switzerland Active, not recruiting
Novartis Investigative Site | Leeds, LS1 3EX, United Kingdom Completed
Novartis Investigative Site | Liverpool, L12 2AP, United Kingdom Active, not recruiting
Novartis Investigative Site | London, WC1N 3JH, United Kingdom Recruiting
Location Countries

Argentina

Australia

Belgium

Brazil

Canada

Czechia

Denmark

Finland

France

Germany

Israel

Italy

Japan

Netherlands

Russian Federation

Spain

Sweden

Switzerland

United Kingdom

United States

Verification Date

February 2021

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: HGG cohort: Dabrafenib and trametinib

Type: Experimental

Description: HGG cohort: All patients in the HGG cohort will receive DRB+TMT

Label: LGG cohort: Carboplatin with vincristine

Type: Active Comparator

Description: LGG cohort: Patients randomized 2:1 to either DRB+TMT or active comparator chemotherapy.

Label: LGG cohort: Dabrafenib and trametinib

Type: Experimental

Description: LGG cohort: Patients randomized 2:1 to either DRB+TMT or active comparator chemotherapy.

Patient Data Undecided
Study Design Info

Allocation: Non-Randomized

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov

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