Diagnosis of diffuse intrinsic pontine glioma (DIPG) for decades has relied on imaging studies and clinical findings. Histologic confirmation has been absent with surgical biopsy of brainstem tumors not believed to have acceptable safety. The prognosis of DIPG has remained quite poor and novel therapeutic strategies are needed. This DIPG Biology and Treatment Study (DIPG-BATS) study incorporates a surgical biopsy at presentation using strict preoperative neurosurgical planning and stratifies participants to receive FDA-approved agents chosen on the basis of specific biologic targets. This is the first prospective national clinical trial to examine the feasibility and safety of incorporating surgical biopsy into potential treatment strategies for children with DIPG.
The primary objective of this study is to estimate the overall survival of children and young adults with DIPG in the context of a molecularly based treatment strategy, compared to historical controls (COG ACNS0126). Secondary objectives were to determine the safety and potential morbidity associated with biopsy of classic DIPGs based on imaging and clinical history as well as ability to perform biologic analyses on the biopsy material obtained to guide therapy. At study entry, a MRI-guided frameless or frame-based stereotactic biopsy will be performed approaching the pontine termentum through a trans-cerebellar or trans-frontal route. The exact biopsy location will be determined by the treating neurosurgeon at the designated participating site with the goal of minimizing procedural risk. Treatment directed based on tumor biopsy results requires classification of patients into 1 of 4 potential cohorts: O\^6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status (negative versus positive) and epidermal growth factor receptor (EGFR) overexpression status (negative versus positive).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
53
Phoenix Children's Hospital
Phoenix, Arizona, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Stanford University/Lucile Packard Children's Hospital
Palo Alto, California, United States
University of California, San Francisco
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Nemours Children's Clinic
Jacksonville, Florida, United States
Miami Children's Hospital
Miami, Florida, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, United States
Ann & Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
University of Louisville
Louisville, Kentucky, United States
...and 13 more locations
9-month Overall Survival (OS) Rate
9-month overall survival is the percentage of participants remaining alive 9 months from registration.
Time frame: 9 months
Rate of Lethal Complications From Surgery
The rate of lethal complications from surgery is the percentage of participants dying as a result of surgery.
Time frame: 2 weeks
Grade 3-4 Post-Procedural Surgery-Related Toxicity Rate
Grade 3-4 post-procedural surgery-related toxicity rate is the percentage of participants experiencing at least one grade 3-4 adverse event (AE) during the post-procedural time frame of 14 days attributable to the surgical procedure based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4).
Time frame: 2 weeks
Delay in Radiation Therapy Start
The number of participants delaying the start of radiation therapy by more than 3 weeks due to complications as a result of surgical biopsy to obtain diagnostic tumor sample.
Time frame: 3 weeks
Feasibility Rate of Molecular Approach to Therapy
Feasibility rate of the molecular strategy is based on the percentage of participants either with inadequate tissue from surgical biopsy to confirm DIPG diagnosis and/or with uninterpretable results for identification of EGFR overexpression and MGMT methylation status.
Time frame: 3 weeks
Number of Participants With Grade 3-4 Treatment-Related Toxicity Over Chemoradiation Therapy
Counts any participant experiencing at least one treatment-related grade 3 or 4 adverse event (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) over chemoradiation therapy as reported on case report forms.
Time frame: Adverse events were routinely throughout treatment. Treatment duration was a median of 6.4 months (range 0.4-13.4 months) in this study cohort.
Median Progression Free Survival (PFS)
PFS based on the Kaplan-Meier method is defined as the duration of time \[months (m)\] from study entry to documented disease progression (PD) or death. Participants alive without PD are censored at the date of last disease assessment. For intrinsic pontine brainstem gliomas, only one lesion/mass is present at diagnosis. Comparisons of maximal 2-dimensional measurements, TxW (product of the longest diameter \[width (W)\] and its longest perpendicular diameter \[transverse (T)\]) are used to assess response for this target lesion. PD is 25% or more increase, taking as reference the smallest product observed since the start of treatment, or the appearance of one or more new lesions.
Time frame: Disease assessments using a standard CNS imaging protocol occurred chemoradiation cycles 1 and 2, every other maintenance cycle, every 3 months post-treatment year 1 then annually until PD or therapy change; In this study cohort, follow-up was up to 34m.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.