Molecularly Determined Treatment of Diffuse Intrinsic Pontine Gliomas (DIPG)
Condition: Diffuse Intrinsic Pontine Glioma
MeSH terms: Glioma; Diffuse Intrinsic Pontine Glioma
Intervention: Bevacizumab; Erlotinib; Temozolomide; Radiation
Intervention description: •
Intervention MeSH terms: Bevacizumab; Temozolomide; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: This is not a randomized trial rather participants are classified and therapy is directed based on molecular profile obtained from surgical biopsy.
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 3 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Molecularly Determined Treatment

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

        Participants must meet the following criteria on screening examination to be eligible to
        participate in the study:

          1. Tumor: Newly diagnosed non-disseminated diffuse intrinsic pontine glioma based on
             classic clinical AND radiographic finding.

          2. No prior radiation therapy or chemotherapy.

          3. Age: Patient must be 3 to < 18 years of age at the time of diagnosis.

          4. Performance Score: Karnofsky Performance Scale > 12 y/o >/= 50 or Lansky Performance
             Score for patients < 12y/o 50 assessed within two-weeks prior to enrollment.

          5. Participants must have normal organ and marrow function as defined below within two
             week s prior to enrollment:

               -  Absolute neutrophil count > 1,000/mcL

               -  Platelets > 100,000/mcL (transfusion independent)

               -  Hemoglobin > 8gm/dL (can be transfused)

               -  Hepatic: Total bilirubin < 1.5 times the upper limit of normal; alanine
                  aminotransferase [SGPT (ALT)] and aspartate aminotransferase [SGOT (AST)] < 5
                  times the institutional upper limit of normal.

               -  Renal: Serum creatinine which is less than 1.5x the upper limit of institutional
                  normal for age or Glomerular Filtration Rate (GFR) > 70 ml/min/1.73m2.

          6. Female patients of childbearing potential must have negative serum or urine pregnancy
             test. Patient must not be pregnant or breast feeding.

          7. Patients of childbearing or child-fathering potential must be willing to use a
             medically acceptable form of birth control, which includes abstinence, while being
             treated on this study.

          8. Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Patients must not have any significant medical illnesses that in the investigator's
             opinion cannot be adequately controlled with appropriate therapy or would compromise
             the patient's ability to tolerate this therapy.

          2. Patients receiving any other anticancer or experimental drug therapy.

          3. Patients with disseminated intrinsic diffuse brainstem gliomas in either brain or
             spine (can be based on clinical evaluation).

          4. Participants receiving any medications or substances that are strong/intermediate
             inhibitors or inducers of Cytochrome P450 (CYP450), Cytochrome P3A4(CYP3A4) or
             Cytochrome 1A2 (CYP1A2) are ineligible. Lists including medications and substances
             known or with the potential to interact with the CYP450 CYP3A4 or CYP1A2 isoenzymes
             are provided in Appendix I.

          5. Use of hematopoietic growth factors within the 2 weeks prior to initiation of therapy.

          6. Patients with evidence of spontaneous hemorrhage greater than 0.5cm unrelated to
             surgery.

          7. Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          8. Pregnant women are excluded from this study because bevacizumab, temozolomide and
             erlotinib can have potential for teratogenic or abortifacient effects. Because there
             is an unknown but potential risk of adverse events in nursing infants secondary to
             treatment of the mother with these agents, breastfeeding should be discontinued.

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