Molecularly Determined Treatment of Diffuse Intrinsic Pontine Gliomas (DIPG)



Status:Completed
Conditions:Brain Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:3 - 18
Updated:7/20/2018
Start Date:September 2011
End Date:March 2017

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Phase II Trial of Molecularly Determined Treatment of Children and Young Adults With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas

The primary objective of this study is to estimate the overall survival of children and young
adults with diffuse intrinsic pontine glioma treated (DIPG) with a molecularly based
treatment strategy, compared to historical controls.

Four Biopsies of tumor tissue will be obtained by surgical biopsy prior to treatment
stratification if tolerated. An 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.

Following biopsy,all patients will receive local radiotherapy to consist of 59.4Gy delivered
using conventional conformal or other standard treatment planning with adjuvant bevacizumab.
Radiation planning can begin with the pre-operative images. Based upon molecular parameters
after biopsy, patients will potentially receive erlotinib and/or temozolomide at the start of
radiotherapy. Bevacizumab will be given concurrently with radiotherapy beginning at least
three weeks from the biopsy and at least two weeks after the start of radiation therapy to
ensure that primary wound healing has occurred. Once irradiation is complete, patients will
have a four week interim period before beginning the maintenance phase. Adjuvant chemotherapy
will be continued during the interim period.

The maintenance phase (approxmiately 40 weeks) will last for 10 cycles(28 days +/- 3 days).
Based upon molecular parameters as determined at the time of diagnostic biopsy, patients will
continue to receive erlotinib and/or temozolomide along with bevacizumab during the
maintenance phase.

Stratification will be based on O6-methylguanine-DNA methyltransferase (MGMT) promoter
methylation status and epidermal growth factor receptor (EGFR) expression in tumor biopsy
samples. If MGMT status and/or EFGR status are not determinable, patients may be treated as
per cohort #1(bevacizumab and irradiation) but will be analyzed separately.


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.
We found this trial at
23
sites
Durham, North Carolina 27710
(919) 684-8111
Duke University Younger than most other prestigious U.S. research universities, Duke University consistently ranks among...
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807 Childrens Way
Jacksonville, Florida 32207
(904) 697-3600
Nemours Children's Clinic At Nemours Children’s Clinic, Jacksonville, we've treated every child as we would...
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Jacksonville, FL
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4650 Sunset Blvd
Los Angeles, California 90027
 (323) 660-2450
Childrens Hospital Los Angeles Children's Hospital Los Angeles is a 501(c)(3) nonprofit hospital for pediatric...
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3100 SW 62nd Ave
Miami, Florida 33155
(305) 666-6511
Miami Children's Hospital Welcome to Miami Children
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1405 Clifton Road NE
Atlanta, Georgia 30322
404-785-6000
Children's Healthcare of Atlanta Whether treating a toddler in an emergency or supporting a teen...
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13123 E 16th Ave
Aurora, Colorado 80045
(720) 777-1234
Children's Hospital Colorado At Children's Hospital Colorado, we see more, treat more and heal more...
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Baltimore, Maryland 21218
(410) 516-8000
Johns Hopkins The Johns Hopkins University opened in 1876, with the inauguration of its first...
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450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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171 Ashley Avenue
Charleston, South Carolina 29425
843-792-1414
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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225 E Chicago Ave
Chicago, Illinois 60611
(312) 227-4000
Ann & Robert H. Lurie Children's Hospital of Chicago Ann & Robert H. Lurie Children
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2201 Inwood Rd
Dallas, Texas 75235
(214) 645-8300
U.T. Southwestern Medical Center The story of UT Southwestern Medical Center is one of commitment...
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3901 Beaubien St
Detroit, Michigan 48201
(313) 745-5437
Children's Hospital of Michigan Since 1886, the Children's Hospital of Michigan has been dedicated to...
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801 7th Avenue
Fort Worth, Texas 76104
(682) 885-4000
Cook Children's Medical Center Cook Children's Health Care System is a not-for-profit, nationally recognized pediatric...
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Hershey, Pennsylvania 17033
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500 S Preston St
Louisville, Kentucky
(502) 852-5555
University of Louisville The University of Louisville is a state supported research university located in...
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Minneapolis, Minnesota 55404
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70 Washington Square S
New York, New York 10012
(212) 998-1212
New York University More than 175 years ago, Albert Gallatin, the distinguished statesman who served...
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1919 E Thomas Rd
Phoenix, Arizona 85006
(602) 933-1000
Phoenix Children's Hospital Phoenix Children's Hospital has provided hope, healing, and the best healthcare for...
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Portland, Oregon 97239
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Saint Louis, Missouri 63110
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San Francisco, California 94143
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4800 Sand Point Way NE
Seattle, Washington 98105
(206) 987-2000
Seattle Children's Hospital Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental...
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