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Molecular Profiling for Individualized Treatment Plan for DIPG

Primary Purpose

Diffuse Intrinsic Pontine Glioma (DIPG)

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Specialized tumor board recommendation
Standard radiation therapy
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Intrinsic Pontine Glioma (DIPG)

Eligibility Criteria

undefined - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria for Newly Diagnosed Patients with diffuse intrinsic pontine glioma (DIPG):

  • Diagnosis: Patients with newly diagnosed DIPG, defined as tumors with a pontine epicenter and diffuse involvement of the pons who undergo a biopsy are eligible. Patients with disseminated disease are not eligible, and MRI of the spine must be performed if disseminated disease is suspected by the treating physician.
  • Enrollment within 28 days of the date of radiographic diagnosis.
  • Age ≤ 25 years
  • Karnofsky score ≥ 50 for patients ≥ 16 years of age and Lansky score ≥ 50 for patients ≤15 years of age. Patients who are unable to walk because of paralysis but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score .
  • Organ Function Requirements:
  • Adequate Bone Marrow Function Defined as:
  • Peripheral absolute neutrophil count (ANC) ≥ 1000/mm 3
  • Platelet count ≥ 100,000/mm 3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • Hemoglobin ≥ 8 g/dl (can be transfusion dependent)
  • Adequate Renal Function Defined as:

Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70ml/min/1.73 m 2 OR a serum creatinine within normal limits based on age/gender as follows:

Maximum Serum Creatinine (mg/dL)

Age Male Female 3 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4

≥ 16 years 1.7 1.4

The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the United States Centers for Disease Control and Prevention (CDC).

  • Organ Function Requirements cont.
  • Adequate Liver Function Defined as:
  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic pyruvic transaminase (SGPT) (ALT) ≤ 110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
  • Serum albumin ≥ 2 g/dL
  • The effects of the current treatment paradigm on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception: hormonal or barrier method of birth control; abstinence prior to study entry and for the duration of study participation, and 30 days after completion of study drug administration. Should a female become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 30 days after completion of study drug administration
  • Adequate Neurologic Function Defined as:
  • Patients with seizure disorder may be enrolled if seizures are well controlled.
  • Ability by patient or parent/legal guardian (for patients under 18 years of age) to understand a written informed consent document, and the willingness to sign it.

Exclusion Criteria for Newly Diagnosed Patients with DIPG:

  • Patients who are currently taking any anti-cancer directed therapy. Steroids are not considered anti-cancer therapy.
  • 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.
  • Female patients of childbearing potential must not be pregnant or breast-feeding. Female patients of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy.
  • Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.

Sites / Locations

  • Rady Children's Hospital
  • University of California, San Francisco
  • Children's National Medical Center
  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • University of Utah

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

The treatment plan for each patient is individualized and different depending on what the Specialized Tumor Board recommends depending on the molecular profile of the patient's tumor.

Outcomes

Primary Outcome Measures

To determine OS12 of children with newly diagnosed DIPG that are being treated based on a specialized tumor board recommendation which is based on RNA based expression analysis, WES and predictive modeling.

Secondary Outcome Measures

Full Information

First Posted
October 21, 2014
Last Updated
November 2, 2022
Sponsor
University of California, San Francisco
Collaborators
Translational Genomics Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02274987
Brief Title
Molecular Profiling for Individualized Treatment Plan for DIPG
Official Title
A Pilot Trial Testing the Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan in Children With Newly Diagnosed DIPG
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
September 16, 2014 (Actual)
Primary Completion Date
December 19, 2018 (Actual)
Study Completion Date
February 24, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Francisco
Collaborators
Translational Genomics Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a single arm multi-center pilot trial within the Pacific Pediatric Neuro-Oncology Consortium (PNOC). The current study will use a new treatment approach based on each patient's tumor genomic profiling consisting of whole exome sequencing and RNA sequencing as well as predictive modeling.
Detailed Description
The current study will test whether patients gain a clinical benefit from such a treatment approach by comparing overall survival at 12 months (OS12) to historical controls. Newly diagnosed patients will receive an individualized treatment recommendation including up to four FDA approved drugs based on the molecular profile of the patient's tumor as determined by gene expression analysis, Whole-exome sequencing (WES) and predictive modeling, age of the patient and other existing medical conditions. Initial therapy will consist of standard radiation therapy per institutional guidelines followed by molecular based therapy with FDA approved drugs.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Intrinsic Pontine Glioma (DIPG)

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
The treatment plan for each patient is individualized and different depending on what the Specialized Tumor Board recommends depending on the molecular profile of the patient's tumor.
Intervention Type
Other
Intervention Name(s)
Specialized tumor board recommendation
Intervention Description
A combination of up to four FDA approved drugs based on the molecular profile of the patient's tumor as determined by gene expression analysis, WES and predictive modeling.
Intervention Type
Radiation
Intervention Name(s)
Standard radiation therapy
Intervention Description
Initial therapy will consist of standard radiation therapy per institutional guidelines followed by molecular based therapy with FDA approved drugs.
Primary Outcome Measure Information:
Title
To determine OS12 of children with newly diagnosed DIPG that are being treated based on a specialized tumor board recommendation which is based on RNA based expression analysis, WES and predictive modeling.
Time Frame
12 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria for Newly Diagnosed Patients with diffuse intrinsic pontine glioma (DIPG): Diagnosis: Patients with newly diagnosed DIPG, defined as tumors with a pontine epicenter and diffuse involvement of the pons who undergo a biopsy are eligible. Patients with disseminated disease are not eligible, and MRI of the spine must be performed if disseminated disease is suspected by the treating physician. Enrollment within 28 days of the date of radiographic diagnosis. Age ≤ 25 years Karnofsky score ≥ 50 for patients ≥ 16 years of age and Lansky score ≥ 50 for patients ≤15 years of age. Patients who are unable to walk because of paralysis but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score . Organ Function Requirements: Adequate Bone Marrow Function Defined as: Peripheral absolute neutrophil count (ANC) ≥ 1000/mm 3 Platelet count ≥ 100,000/mm 3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) Hemoglobin ≥ 8 g/dl (can be transfusion dependent) Adequate Renal Function Defined as: Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70ml/min/1.73 m 2 OR a serum creatinine within normal limits based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age Male Female 3 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4 ≥ 16 years 1.7 1.4 The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the United States Centers for Disease Control and Prevention (CDC). Organ Function Requirements cont. Adequate Liver Function Defined as: Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age Serum glutamic pyruvic transaminase (SGPT) (ALT) ≤ 110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L. Serum albumin ≥ 2 g/dL The effects of the current treatment paradigm on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception: hormonal or barrier method of birth control; abstinence prior to study entry and for the duration of study participation, and 30 days after completion of study drug administration. Should a female become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 30 days after completion of study drug administration Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if seizures are well controlled. Ability by patient or parent/legal guardian (for patients under 18 years of age) to understand a written informed consent document, and the willingness to sign it. Exclusion Criteria for Newly Diagnosed Patients with DIPG: Patients who are currently taking any anti-cancer directed therapy. Steroids are not considered anti-cancer therapy. 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. Female patients of childbearing potential must not be pregnant or breast-feeding. Female patients of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy. Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sabine Mueller, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rady Children's Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data after de-identification.

Learn more about this trial

Molecular Profiling for Individualized Treatment Plan for DIPG

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