Clinical trial NCT03739372: Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan for Patients With High Grade Glioma
Official title: A Pilot Trial Testing the Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan in Children and Young Adults With High Grade Glioma (Excluding Diffuse Intrinsic Pontine Glioma)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Glioma
Glioma of Brain
Cancer
Pediatric Cancer
Pediatric Brain Tumor
Astrocytoma
Glioblastoma
Hemispheric
Keywords: High-grade glioma
whole exome sequencing
WES
genomics
RNA sequencing
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Pacific Pediatric Neuro-Oncology Consortium
name: The V Foundation for Cancer Research
First posted: 2018-11-13
Enrollment: 44
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a 2 strata pilot trial within the Pacific Pediatric Neuro-Oncology Consortium (PNOC).

The study will use a new treatment approach based on each patient's tumor gene expression, whole-exome sequencing (WES), targeted panel profile (UCSF 500 gene panel), and RNA-Seq. The current study will test the efficacy of such an approach in children with High-grade gliomas HGG.

Detailed description: For children with High-grade gliomas (HGG) including HGG presenting within the midline structures of the brain and spine, outcome remains poor and the majority of children die from this disease. The current study will use a new treatment approach based on each patient's tumor gene expression, whole-exome sequencing (WES), targeted panel profile (UCSF 500 gene panel), and RNA-Seq. This treatment strategy has shown promising results in adult patients with solid tumors and is currently being explored in children with DIPG, neuroblastoma and other solid tumors. The current study will test the efficacy of such an approach in children with HGG for which outcomes remain dismal.

Eligibility criteria: Inclusion Criteria:

* Patients with newly diagnosed HGG (including midline HGG but excluding DIPG), who undergo tissue collection as part of standard of care. HGG is defined as either World Health Organization (WHO) grade III or IV, or testing positive for H3K27M mutation. Patients with disseminated disease are not eligible, and MRI of the spine must be performed if disseminated disease is suspected by the treating physician. Primary spinal cord tumors are eligible.
* Enrollment within 3 weeks of the start of radiation therapy.
* Start of radiation therapy within 6 weeks from initial tissue diagnosis.
* Age ≤ 21 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
* Adequate tissue for molecular profiling (see Section 8 of the protocol for full details)
* The effects of the current treatment paradigm on the developing human fetus are unknown. For this reason, females of child-bearing potential and males 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. Males 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 to understand a written informed consent document, and the willingness to sign it.

Exclusion Criteria:

* Patients who are currently enrolled on another therapeutic clinical trial. Individual cases should be discussed with the study chair.
* Patients who are currently taking any anti-cancer directed therapy. Steroids are not considered anti-cancer therapy. The use of temozolomide during radiation therapy is allowed at standard dosing (maximum 75 to 90 mg/m\^2 daily for a total of 42 days). Any other schedule(s) need to be discussed with the study chair.
* 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 (as clinically indicated).
* Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy. Telemedicine visits are acceptable.

Primary outcomes:
measure: 12 month Progression Free Survival (PFS) for Stratum A
timeFrame: Up to 12 months
measure: 12 month Overall Survival (OS) for Stratum B
timeFrame: Up to 12 months
Secondary outcomes:
measure: Frequency of Adverse Events
timeFrame: From beginning of enrollment up to 30 days post end of treatment.
measure: Frequency of Serious Adverse Events
timeFrame: From beginning of enrollment up to 30 days post end of treatment.
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego Rady Children's Hospital
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minneapolis
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital Of Philadelphia
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: University of California, San Francisco
name: Sabine Mueller, MD, PhD, MAS
role: PRINCIPAL_INVESTIGATOR
References: