Molecularly Determined Treatment of Diffuse Intrinsic Pontine Gliomas (DIPG)

• Status: Terminated
• Trial end date: 2016-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dana-Farber Cancer Institute; Karen D. Wright MD
• Collaborators: Ann & Robert H Lurie Children's Hospital of Chicago; Boston Children's Hospital; Boston Children’s Hospital; Children's Healthcare of Atlanta; Children's Hospital Colorado; Children's Hospital Los Angeles; Children's Hospital of Michigan; Children's Hospitals and Clinics of Minnesota; Children's National Research Institute; Cook Children's Medical Center; Doernbecher Children's Hospital; Duke University; Johns Hopkins University; Lucile Packard Children's Hospital; Medical University of South Carolina; Milton S. Hershey Medical Center; Nemours Children's Clinic; Nemours Children's Clinic Jacksonville; New York University; Nicklaus Children's Hospital f/k/a Miami Children's Hospital; OHSU Doernbecher Children's Hospital; Phoenix Children's Hospital; Seattle Children's; Seattle Children's Hospital; University of California, San Francisco; University of Louisville; UT Southwestern Medical Center; Washington University School of Medicine
• Treatments: Bevacizumab; Dacarbazine; Erlotinib Hydrochloride; Temozolomide

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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