Molecular Profiling for Individualized Treatment Plan for DIPG

A Pilot Trial Testing the Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan in Children With Newly Diagnosed DIPG

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.

Study Overview

• Status: Completed
• Conditions: Diffuse Intrinsic Pontine Glioma (DIPG)
• Intervention / Treatment: Other: Specialized tumor board recommendation; Radiation: Standard radiation therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Rady Children's Hospital
    • San Francisco, California, United States, 94158
      • University of California, San Francisco
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 25 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment; 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.

Other: Specialized tumor board recommendation; 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.; Radiation: Standard radiation therapy; Initial therapy will consist of standard radiation therapy per institutional guidelines followed by molecular based therapy with FDA approved drugs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	12 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Translational Genomics Research Institute
• Investigators: Principal Investigator: Sabine Mueller, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2014
• Primary Completion (Actual): December 19, 2018
• Study Completion (Actual): February 24, 2019

Study Registration Dates

• First Submitted: October 21, 2014
• First Submitted That Met QC Criteria: October 22, 2014
• First Posted (Estimate): October 27, 2014

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Stem Neoplasms; Infratentorial Neoplasms; Diffuse Intrinsic Pontine Glioma
• Other Study ID Numbers: PNOC 003; 14082 (Other Identifier: University of California, San Francisco)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data after de-identification.
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No