DRBHGG: Combination Chemotherapy for Low Grade Glioma (LGG) and Relapsed or Refractory High Grade Glioma (HGG) Brain Tumors

Dabrafenib in combination with trametinib in pediatric patients with BRAF V600 mutation positive, newly diagnosed low grade glioma (LGG) or relapsed or refractory high grade glioma (HGG)

Categories:

Brain Tumor

Phase I/II

Diseases Treated:

High grade glioma (HGG), low grade glioma (LGG)

Eligibility Overview:

  • At least 12 months old and younger than 18 years of age
  • High grade glioma with BRAF V600 mutation that has relapsed, progressed or failed to respond to therapy OR
  • Newly diagnosed Low grade glioma with BRAF V600 mutation that is not treatable with surgery and no previous treatment with chemotherapy, radiotherapy or targeted agents.
  1. Brief Summary

    DRBHGG is a Phase II, open-label global study to evaluate the effect of dabrafenib in combination with trametinib in children and adolescents with BRAF V600 mutation-positive low grade glioma (LGG) or relapsed or refractory high grade glioma (HGG).

    In a prior pediatric Phase I/IIa clinical trial of dabrafenib monotherapy, about one-third of patients with relapsed or refractory BRAF V600 mutant HGG had confirmed responses. Previous studies in adults have shown a combination therapy of dabrafenib and trametinib results in better outcomes than dabrafenib alone.

    Participants in this clinical trial will receive oral dabrafenib twice daily and trametinib once daily. All patients will be followed for survival for at least two years after the last study treatment.

    Primary Objective

    • To evaluate the anti-tumor activity of dabrafenib in combination with trametinib as measured by overall response rate (ORR) to the combination therapy

    Eligibility Criteria

    Inclusion criteria include:

    • At least 12 months old and younger than 18 years of age
    • High grade glioma with BRAF V600 mutation that has relapsed, progressed or failed to respond to therapy OR
    • Newly diagnosed Low grade glioma with BRAF V600 mutation that is not treatable with surgery and no previous treatment with chemotherapy, radiotherapy or targeted agents.
    • Exclusion criteria include:
    • Prior treatment with dabrafenib, trametinib, other RAF inhibitor, other MEK or ERK inhibitor
    • HGG patients: Cancer treatment within 3 weeks prior to starting study
    • HGG patients: Radiotherapy to CNS glioma lesions within 3 months prior to first dose of study treatment, unless there is clear evidence of radiologic progression outside of the field of radiation.
    • LGG patients: Any systemic anticancer therapy (chemotherapy, immunotherapy, biologic therapy, or vaccine therapy) or investigational drugs prior to enrollment.

    Study Sites

    St. Jude Children’s Research Hospital, Memphis, Tennessee
    Collaborating sites in and outside the U.S.

  2. About this study

    This study looks at how well two experimental drugs work when given to children and adolescents in patients with low grade glioma (LGG) and high grade glioma (HGG) brain tumors that have a mutation (change) in the BRAF gene. The two experimental drugs are dabrafenib and trametinib. The U.S. Food and Drug Administration (FDA) has approved this drug combination for the treatment of adults with melanoma, a type of skin cancer. The FDA has not approved the drugs to treat these types of brain tumors.

    There is no standard treatment for high grade glioma that has come back after treatment (relapsed) or not responded to treatment (refractory).  Therapies that have been used previously include surgery, chemotherapy, radiation therapy, or other comfort care without the intent to control tumor growth.

    This study will evaluate the anti-tumor activity of dabrafenib in combination with trametinib in patients with relapsed or progressive HGG who have failed standard frontline therapy. The study will also compare this drug combination to standard chemotherapy treatment in patients with newly diagnosed low grade glioma.

    Purpose of this clinical trial

    The main goal of this study is to find out the good and bad effects of these drugs in children and adolescents with these brain tumors. We also want to understand more about how these drugs work in children, teens and young adults.

    • At least 12 months old and younger than 18 years of age
    • High grade glioma with BRAF V600 mutation that has relapsed, progressed or failed to respond to therapy OR
    • Newly diagnosed low grade glioma with BRAF V600 mutation that is not treatable with surgery and no previous treatment with chemotherapy, radiotherapy or targeted agents.
  3. DBRHGG  Quick View
    Sponsor Novartis
    ClinicalTrials.gov identifier NCT02684058
    Trial start date December 2017
    Estimated enrollment 142 (5 at St. Jude)
    Study type Interventional
    Study phase Phase II
    Conditions

    Glioma

    Ages ≥12 months and <18 years of age
    Principal investigator Santhosh Upadhyaya, MD
    Study site St. Jude Children’s Research Hospital and collaborating sites outside the U.S.
    For a consultation or to discuss DBRHGG St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org