Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioma

Brain Neoplasms

Diffuse Intrinsic Pontine Glioma

Brain Stem Neoplasms

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Infratentorial Neoplasms

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Vaccines

Rindopepimut

Antineoplastic Agents, Immunological

Paul Graham Fisher

This is a research study of patients with diffuse intrinsic pontine gliomas. We hope to learn about the safety and efficacy of treating pediatric diffuse intrinsic pontine glioma patients with the EGFRvIII peptide vaccine after conventional radiation.

Phase I Rindopepimut After Conventional Radiation in Children w/ Diffuse Intrinsic Pontine Gliomas

A Phase I Study of Rindopepimut After Conventional Radiation in Children With Diffuse Intrinsic Pontine Gliomas

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Professor of Pediatrics

Anti-Infective Agents

Amino Acids

Everolimus

Mitogens

Dasatinib

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Tyrosine Kinase Inhibitors

Tyrosine

Dasatinib = 60 mg/m2 orally twice daily

Everolimus = starting dose of 3.0 mg/m2, with titration of dosing after first cycle to keep everolimus trough level of 5-15 ug/ml

Both agents will be taken daily for 28 day cycles. Cycles will be repeated every 28 days and patients may receive up to 24 cycles.

3.0 mg/m2, with titration of dosing after first cycle to keep trough level of 5-15 ug/ml

Carl Koschmann, M.D.

This trial will evaluate the activity of dasatinib in combination with everolimus for children with gliomas harboring PDGFR alterations, including newly diagnosed high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG) after radiation (stratum A); and recurrent/progressive glioma (grade II-IV, including DIPG) (stratum B).

Study of Dasatinib in Combination With Everolimus for Children and Young Adults With Gliomas Harboring Platelet-Derived Growth Factor Receptor (PDGFR) Alterations

A Phase 2 Study of Dasatinib in Combination With Everolimus for Children With Gliomas Harboring PDGFR Alterations

Percentage of participants without progression, defined as 25% increase in the size of the tumor or appearance of new lesions.

The overall response assessment will take into account response in both target and non-target lesions, as well as the appearance of new lesions. Partial Response (PR) will be defined as ≥50% decrease in size of tumor in comparison to baseline measurements. Complete Response (CR) will be defined as the disappearance of all abnormal signal. This includes return to normal size of the brain stem for brain stem lesions. Reported as percentage of participants with partial or better response at 56 days.

Percentage of patients alive at one year.

Percentage of participants alive at 2 years.

University of Michigan Rogel Cancer Center

Dasatinib+Everolimus

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Trial enrollment was limited due to requirement for patient insurance coverage for all aspects of treatment. Due to limited sample size, full statistical analysis isn't possible. Descriptive results of this cohort compiled with data available from patients treated locally with a similar treatment plan is available in the following publication: Miklja et al, JCI, 2020 \[PMID: 32603316\].

Carl Koschmann, MD

Progression-free Survival in Participants With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)

Progression-free Survival in Participants With Newly Diagnosed High-grade Glioma (HGG)

Overall Response Rate (OR) (Partial Response or Better) in Participants With Refractory or Recurrent Glioma

Overall Survival

Overall Study

Any other dose and fractionation for primary radiotherapy than 54gy/30 fractions.

Re-irradiation

Daniella Østergaard

Maja V. Maraldo

Maja V Maraldo

The REMIT (RE-irradiation of diffuse MIdline glioma paTients) study evaluates safety and the palliative efficacy of re-irradiation of patients with diffuse midline glioma (DMG). The study will introduce a standard re-irradiation treatment schedule for DMG patients who have progressed following primary treatment.

REMIT is a non-randomized, prospective, investigator-initiated, phase II, multi-centre observational study with two inclusion groups, arm A and B. Arm A and B will be offered the same treatment.

Patients treated with primary radiotherapy 54Gy/30 fractions, either enrolled in the BIOMEDE 2.0 protocol or not, will be included in Arm A. DMG patients treated with any other total dose and fractionation than 54Gy/30F will be included in Arm B. The re-RT and follow up will be the same in both arms.

As treatment 20Gy/10 fractions is given as first time re-irradiation with extended follow up on toxicity, performance status and quality of life.

RE-irradiation of Diffuse MIdline Glioma paTients

All data will be collected in a RedCap database.

* Delineation study A comparison of variations in delineation in tumour volume among the participating institutions. This will improve the delineation-related uncertainty and, consequently, the applied margins (and hence irradiated volume) can be diminished. This will ensure a more uniform treatment across countries.
* The impact of reRT on the patients and their families An analysis of the value of reRT in terms of the practical, emotional, and existential impact on patients and their families. This will be done by using a qualitative method including interviewing the parents of a subgroup of the included patients.
* Referral patterns A characterisation of referral patterns of DMG patients to reRT. This will be assessed through a screenings log of all DMG patients in the participating institutions. Date of diagnosis, date of death, reRT offered yes/no, and reason for not giving reRT will be registered prospectively.

The primary endpoint will be the cumulative incidence of grade ≥4 CTCAE (The NCI Common Terminology Criteria for Adverse Events) events measured 4 weeks after the last day of reRT.

Palliative efficacy measured as overall survival will be reported as 1) from date of diagnosis to date of death by any cause, and 2) from date of first radiological and/or clinical progression to date of death by any cause.

Symptom relief measured by 1) clinical performance status (Karnofsky or Lansky) assessed every second week, 2) a modified PEDI score before, during and 4 weeks after reRT, 3) steroid dose levels measured every second week, and 4) quality of life monitored before, during and 4 weeks after re-irradiation with PedsQL Cancer module questionnaire.

Other secondary objectives are further defined as:

* Image-guided characterization of the anatomical site of progression compared to the primary lesion.
* Assessment of cumulated radiation dose to critical structures in the brain following the initial and reRT treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Rindopepimut After Conventional Radiation in Children w/ Diffuse Intrinsic Pontine Gliomas	NCT01058850	Brain Cancer Brain Stem Tumo... Pontine Tumors	Rindopepimut	3 Years - 18 Years	Stanford University
Phase I Rindopepimut After Conventional Radiation in Children w/ Diffuse Intrinsic Pontine Gliomas	NCT01058850	Brain Cancer Brain Stem Tumo... Pontine Tumors	Rindopepimut	3 Years - 18 Years	Stanford University
Study of Dasatinib in Combination With Everolimus for Children and Young Adults With Gliomas Harboring Platelet-Derived Growth Factor Receptor (PDGFR) Alterations	NCT03352427	Glioma High Grade Glio... Pontine Tumors	Dasatinib Everolimus	1 Year - 50 Years	University of Michigan Rogel Cancer Center
RE-irradiation of Diffuse MIdline Glioma paTients	NCT06093165	Diffuse Midline... Diffuse Intrins... Diffuse Glioma Pontine Tumors Thalamic Tumor Brain Tumor, Pe...	Re-irradiation	12 Months - 21 Years	Rigshospitalet, Denmark

Spots Global Cancer Trial Database for pontine tumors