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)
Trial Requirements and Treatment
Patients with newly diagnosed high grade glioma (including midline and excluding DIPG) who have undergone surgery as part of their standard of care and can provide the necessary tumor tissue for analysis will be eligible for this study. The tissue will be sent for detailed profiling. After the surgery, patients will be treated with focal irradiation per institutional guidelines. After completion of radiation therapy, patients will follow the specialized tumor board recommendation. The treatment will be based on each child’s individual tumor profile and will include up to 4 medications. Depending on the individual treatment plan, the tumor board will also recommend required study observations to assure safety for the patient.
Rationale for Study
Despite years of research and multiple clinical trials in patients with High Grade Gliomas, no significant survival advantage has been achieved. This study will use an individualized treatment approach based on whole exome sequencing (WES), genomic profile from whole genome sequencing (WGS), a targeted panel approach (UCSF 500 gene panel), each patient’s tumor quantitative proteomic profile, detected by mass spectrometry, and transcriptome profile as determined by gene expression analysis (RNA sequencing). The proteomic, transcriptomic and genomic profiling will be performed in collaboration with the genomics team at UCSF as well as NantOmics. We have shown that it is feasible to perform detailed profiling of DIPG specimens (PNOC003; NCT02274987) and that a therapy recommendation can be issued within 21 business days. We have also shown that there are no major safety concerns with regard to being treated with an individualized therapy plan with up to 4 FDA approved drugs in combination.
- To determine the progression free survival at 12 months of children and young adults with newly diagnosed High Grade Glioma who underwent maximal safe surgical resection followed by focal radiation therapy who are being treated according to a specialized tumor board recommendation that is based on WES, WGS, targeted panel (UCSF500 gene panel), quantitative proteomics, and RNA-Seq analysis of the tumor.
- To determine the overall survival at 12 months in children with newly diagnosed midline High Grade Glioma (excluding DIPG) who underwent maximal safe surgical resection followed by focal radiation therapy who are being treated according to a personalized treatment recommendation that is based on WES, WGS, targeted panel (UCSF 500 gene panel), quantitative proteomics, and RNA seq analysis of the tumor.
- To determine the safety and describe the toxicity of treating children and young adults with newly diagnosed High Grade Glioma who underwent maximal safe surgical resection followed by focal radiation therapy who are being treated) according to a specialized tumor board recommendation that is based on WES, WGS, targeted panel (UCSF500 gene panel), quantitative proteomics, and RNA-Seq analysis of the tumor.
Subjects must have baseline evaluations performed prior to start of protocol treatment and must meet all inclusion and none of the exclusion criteria. In addition, the patient and/or their legal guardian must be thoroughly informed about all aspects of the study, including the study visit schedule, required evaluations and all regulatory requirements. The written informed consent must be obtained from the patient or their legal guardian prior to enrollment. The following criteria apply to all patients enrolled onto the study unless otherwise specified.
Stratum A: Children (≤ 21 years old) with newly diagnosed High Grade Glioma (HGG)
Stratum B: Children (≤ 21 years old) with newly diagnosed diffuse midline High Grade Glioma (excluding DIPG)
The following inclusion criteria apply to both Stratum A and B:
- Diagnosis: Patients with newly diagnosed HGG (including midline HGG but excluding DIPG), who underwent maximal safe surgical resection followed by focal radiation therapy as part of standard of care, 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. 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 (see Appendix A).
- Adequate tissue for molecular profiling (>25% tumor content).
- 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.
- 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/m2 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.
Important Note: The eligibility criteria listed above are interpreted literally and cannot be waived.
How to Enroll
If you believe your child or patient is eligible for this trial, contact the closest participating site for more information or contact us at firstname.lastname@example.org.