Molecular Profiling for Individualized Treatment Plan for DIPG

• ClinicalTrials.gov Identifier: NCT02274987
• Recruitment Status: Completed
• First Posted: October 27, 2014
• Last Update Posted: November 4, 2022
• Sponsor: University of California, San Francisco
• Collaborator: Translational Genomics Research Institute
• Information provided by (Responsible Party): Sabine Mueller, MD, PhD, University of California, San Francisco

Tracking Information

• First Submitted Date: October 21, 2014
• First Posted Date: October 27, 2014
• Last Update Posted Date: November 4, 2022
• Actual Study Start Date: September 16, 2014
• Actual Primary Completion Date: December 19, 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 12, 2016): 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 ]

Original Primary Outcome Measures (submitted: October 22, 2014)

Number of patients for whom an individualized treatment plan is provided within 21 business days [ Time Frame: Within 21 business days of tumor tissue collection ]

A specialized tumor board will make individualized treatment recommendations, using RNA based expression analysis, whole exome sequencing (WES) and predictive modeling

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diffuse Intrinsic Pontine Glioma (DIPG)

Intervention

• 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.

Study Arms

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.

Interventions:

• Other: Specialized tumor board recommendation
• Radiation: Standard radiation therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 14, 2018): 38
• Original Estimated Enrollment (submitted: October 22, 2014): 15
• Actual Study Completion Date: February 24, 2019
• Actual Primary Completion Date: December 19, 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 25 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02274987
• Other Study ID Numbers: PNOC 003; 14082 ( Other Identifier: University of California, San Francisco )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Individual participant data after de-identification.
• Supporting Materials: Study Protocol

• Current Responsible Party: Sabine Mueller, MD, PhD, University of California, San Francisco
• Original Responsible Party: University of California, San Francisco
• Current Study Sponsor: University of California, San Francisco
• Original Study Sponsor: Same as current
• Collaborators: Translational Genomics Research Institute

Investigators

• Principal Investigator: Sabine Mueller, MD; University of California, San Francisco

• PRS Account: University of California, San Francisco
• Verification Date: November 2022