Non-Invasive Focused Ultrasound (FUS) With Oral Panobinostat in Children With Progressive Diffuse Midline Glioma (DMG)

Launched by COLUMBIA UNIVERSITY · Mar 16, 2021

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for children with a type of brain tumor called diffuse midline glioma (DMG), which is challenging to treat because it grows in a critical area of the brain. The study aims to see if a non-invasive technique called Focused Ultrasound (FUS) can help open the blood-brain barrier temporarily. This barrier usually protects the brain but can also prevent medications from reaching tumors effectively. By using FUS in combination with an oral medication called Panobinostat, the researchers hope to allow more of the drug to enter the tumor, potentially making the treatment more effective while reducing side effects.

To participate in the trial, children between the ages of 4 and 21 who have shown signs of tumor progression may be eligible, provided they are healthy enough for the procedure and can swallow capsules. Participants will undergo FUS treatment at specific locations around the tumor and then take Panobinostat. It’s important to note that children must have recovered from any previous cancer treatments before joining the study. Throughout the trial, participants will be closely monitored for their health and response to the treatment. Parents or guardians will need to give consent for their child to participate and will be informed of the potential risks involved.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Ages 4-21 years.
• • Subjects with evidence of clinical and/or radiographic progression of Diffuse Midline Glioma
• • Radiological diagnosis of DMG with tumor involving the pons (intrinsic, pontine based infiltrative lesion; hypointense in T1 weighted images (T1WIs) and hyperintense in T2 sequences, with mass effect on the adjacent structures and occupying at least 50% of the pons), thalami and/or histological confirmation of H3K27M mutation confirmation of pontine or thalamic glioma.
• * Subjects must be healthy enough to tolerate FUS and MRI and any anesthesia necessary based on the opinion of the principal investigator. Subjects must also be able to swallow capsules (for Panobinostat dosing). Other criteria include, but is not limited to:
• Prior therapy:
• • • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment.
• • Cytotoxic chemotherapy or anti-cancer agents known to be myelosuppressive: At least 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy.
• • Anti-cancer agents not known to be myelosuppressive: At least 7 days must have elapsed from last dose of agent.
• • Antibodies: At least 21 days must have elapsed from infusion of last dose of antibody.
• • Interleukins, Interferons, and Cytokines: At least 21 days must have elapsed since the completion of interleukins, interferon, or cytokines.
• • Stem cell infusions: At least 42 days must have elapsed after completion of an autologous stem cell infusion, and at least 84 days must have elapsed after completion of an allogeneic stem cell infusion.
• • Cellular therapy: At least 42 days must have elapsed since the completion of any type of cellular therapy
• • Radiotherapy (XRT): At least 1 month must have elapsed after local XRT.
• • Subjects must be on a stable or decreasing dose of steroids, as well as stable dose of anti-seizure medication for 1 week.
• Performance status:
• • • Karnofsky performance status or Lansky play score of ≥70
• Hepatic:
• • Total bilirubin: within normal institutional limits
• • Aspartate Aminotransferase (AST, SGOT)/Alanine aminotransferase (ALT, SGPT): ≤ 2.5 × institutional upper limit of normal
• Renal:
• • Creatinine: within normal institutional limits
• • Creatinine clearance: ≥ 60 mL/min/1.73m2 for subjects with creatinine levels above institutional normal
• Hematopoietic:
• • Absolute neutrophil count: ≥ 1,500/μL
• • Platelet count: ≥ 100,000/μL
• • Hemoglobin level: ≥ 10g/dL
• • Partial thromboplastin time (PTT) and activated partial thromboplastin time (aPTT): within normal institutional limits
• • No documented current bleeding disorder
• Other:
• • Not pregnant or nursing - negative serum pregnancy test, if of childbearing potential, within 7 days of study entry
• • Subjects with a history of seizures/epilepsy should be on anti-convulsant medication prior to the first operative procedure on the study.
• • Subjects must undergo a baseline EKG within 7 days of study enrollment.
• • Subjects must be able to undergo MR imaging with gadolinium-based contrast administration (e.g. no ferrous-containing implants, no pacemakers, etc.)
• • All subjects or their legal guardians must sign a document of informed consent indicating their understanding of the investigational nature and the potential risks associated with this study. When appropriate, pediatric subjects will be included in all discussions in order to obtain verbal and written assent
• Exclusion Criteria:
• • Subjects with spinal DMGs.
• • Subjects with a medical condition that would preclude general anesthesia
• • Subjects with evidence of any active infection
• • Subjects with documented allergy to compounds of similar chemical or biologic composition to Panobinostat or gadolinium compounds
• • Subjects with evidence of tumor hemorrhage
• • Subjects with an uncorrectable bleeding disorder
• • Subjects with signs of impending herniation or an acute intratumoral hemorrhage
• • Subjects with systemic diseases which may be associated with unacceptable anesthetic/operative risk
• • Subjects with implanted electrical devices, metallic implants
• • Subjects with uncontrollable hypertension
• • Subjects with a history of stroke or cardiovascular disease
• • Subjects with cerebrovascular diseases
• • Subjects with coagulopathy or under anticoagulant therapy.
• • Pregnant or breast-feeding women will not be entered on this study, since there is yet no available information regarding human fetal or teratogenic toxicities. A pregnancy test must be obtained in girls who are post-menarchal. Males with female partners of reproductive potential or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control- including a medically accepted barrier method of contraception (e.g., a male or female condom) for the entire period in which they are receiving protocol therapy and for at least 1 week following their last study treatment requirement. Abstinence is an acceptable method of birth control.