Phase II open-label global study to evaluate the effect of dabrafenib in combination with trametinib in childeren and adolescent patients with BRAF V600 mutation positive low grade glioma (LGG) or relapsed or refractory High Grade Glioma (HGG)
- Conditions
- braintumorglioma10029211
- Registration Number
- NL-OMON50503
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 5
- Male or female >= 1 and <18 years of age.
- HGG cohort only: Relapsed, progressed, or failed to respond to frontline
therapy.
- LGG cohort: progressive disease following surgical excision, or
non-surgical candidates with necessity to begin first systemic treatment
- Histologically confirmed diagnosis of High Grade Glioma (Grade III or IV
glioma as defined by WHO histological classification system, revised 2016),
including anaplastic pleomorphic xanthoastrocytoma (aPXA) and anaplastic
ganglioglioma.
- LGG defined by WHO histological classification system
- BRAF V600 mutation-positive tumor
- confirmed measurable disease.
- Tumor tissue (archival or newly obtained) must be provided for testing HGG
histopathology and HGG and LGG BRAF mutational status.
- Karnofsky/Lansky performance score of >=50%.
- Adequate bone marrow function in the absence of growth factor support.
- Adequate renal function, liver function, and cardiac function.
- If receiving glucocorticoids, patient must be on a stable or weaning dose for
at least 7 days prior to first dose of study treatment.
- Malignancy OTHER than BRAF V600 mutant HGG and LGG.
- Previous treatment with dabrafenib or another RAF inhibitor, trametinib or
another MEK inhibitor, or an ERK inhibitor.
- HGG: Cancer therapy or investigational drugs within 3 weeks preceding the
first dose of study treatment.
- LGG: Any systemic anticancer therapy or investigational drugs prior to
enrollment.
- HGG: 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: Radiotherapy to CNS glioma lesions at any point prior to enrollment.
- History of malignancy with confirmed activating RAS mutation or with BRAF
fusion such as BRF-KIAA1549.
- Current use of a prohibited medication or herbal preparation or requires any
of these medications during the study. See Section 6.4 for details of the
protocol.
- Unresolved toxicity greater than NCI CTCAE v 4.03 grade 2 from previous
anti-cancer therapy,
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to dabrafenib, trametinib and their excipients. LGG also
history
of allergic reactions or contraindications to the use of carboplatin or
vincristine.
- Autologous or allogeneic stem cell transplant within 3 months prior to the
first dose of study treatment
- History or current diagnosis of cardiac disease indicating significant risk
of safety for patients participating in the study
- Uncontrolled medical conditions, psychological, familial, sociological, or
geographical conditions that do not permit compliance with the protocol; or
unwillingness or inability to follow the procedures required in the protocol.
- Presence of active GI disease or other condition that will interfere
significantly with the absorption of drugs.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective for HGG cohort is: to evaluate the anti-tumor activity<br /><br>of dabrafenib in combination with trametinib as measured by overall response<br /><br>rate (ORR) to the combination therapy by investigator assessment using the RANO<br /><br>criteria.<br /><br><br /><br>The primary objective for LGG cohort is: Compare the anti-tumor activity of<br /><br>dabrafenib in combination with trametinib versus carboplatin with vincristine,<br /><br>as measured by overall response rate (ORR) by central independent assessment<br /><br>using the RANO criteria.</p><br>
- Secondary Outcome Measures
Name Time Method