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About
The primary objectives of this trial are to evaluate the safety and tolerability of sonodynamic therapy (SDT) using SONALA-001 and Exablate Type 2.0 device and to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of MR-Guided Focused Ultrasound (MRgFUS) energy in combination with SONALA-001 in subjects with diffuse intrinsic pontine glioma
Funding Source - FDA OOPD
Enrollment
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Inclusion criteria
DIPG Subjects:
Newly diagnosed, radiographically typical DIPG, defined as a tumor with a pontine epicenter and diffuse involvement of more than ⅔ of the pons and without evidence of dissemination, are eligible with or without histologic confirmation.
Prior treatment consisting of a minimum of 54 Gy standard focal radiotherapy administered over 42-49 days.
Must be ≥ 4 weeks and ≤ 24 weeks post radiotherapy and must have recovered from acute effects to CTCAE (version 5) Grade 1 or baseline prior to Day 1.
Must have stable to improved imaging by RAPNO (subjects ≤ 21 years of age) and mRANO (subjects > 21 years of age) criteria comparing the scan obtained post radiotherapy to the scan obtained during the screening period. The comparison of diagnosis imaging scan and screening imaging scan must be reviewed by the study site's neuroradiologist and the principal investigator. If subjects present within 3 months after completion of radiotherapy and the comparison of the diagnosis scan to the screening scan is consistent with RAPNO/mRANO progression but pseudoprogression is a consideration, then the subject can be re-screened if the subject falls out of the screening window.
Subjects who are on steroids must be on a stable to decreasing dose of steroids (maximum dexamethasone of 1 mg/m2/day) prior to Day 1.
Minimum of 5 years of age. Subjects younger than 5 years old may be eligible after discussion with the Sponsor Medical Monitor/designee.
A minimum head circumference of 52 cm as measured by physical exam. Subjects with a minimum head circumference smaller than 52 cm may be eligible after discussion with the Sponsor Medical Monitor/designee.
Females of childbearing potential (FOCP) must have a negative serum or urine pregnancy test at screening. Subjects of childbearing or child fathering potential must be willing to use highly effective birth control during the entire study. Acceptable forms of birth control include hormonal contraceptives (oral, injectable, transdermal, or intravaginal) or intrauterine device (IUD) for at least one week prior to ALA SDT, condom and spermicidal or diaphragm and spermicidal. Other acceptable forms of birth control include a) abstinence for subjects who are not sexually active; or b) if the subject is in a monogamous relationship with a partner who is sterile (e.g., vasectomy performed at least 6 months prior to subject's ALA SDT treatment). Subjects who become sexually active or begin to have relations with a partner who is not sterile during the trial must agree to use an effective form of birth control for the duration of the study. FOCP taking hormonal therapy must be on treatment for at least 12 weeks prior to study entry and must not change their dosing regimen during the study.
Ability to provide written, signed, and dated (personally or via a legally authorized representative) informed consent/and assent at screening as applicable to participate in the study.
Karnofsky Performance Scale (KPS for > 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within 14 days of Day 1 must be ≥ 50%. Subjects who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Subjects must have adequate organ and marrow function as defined below:
Absolute neutrophil count ≥ 1,000/mm3, without the use of myeloid growth factors (e.g. GCSF) within 7 days prior to Day 1.
Platelets ≥ 100,000/mm3 (unsupported, defined as no platelet transfusion within 7 days prior to Day 1).
Hemoglobin ≥ 8 g/dl maintained without the need for erythropoietin stimulating agents (may have received last transfusion within 7 days prior to Day 1).
Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN); in subjects with Gilbert syndrome, total bilirubin >1.5 ULN as long as direct bilirubin is normal.
Alanine aminotransferase (ALT) < 3 x institutional ULN.
Aspartate aminotransferase (AST) < 3 x institutional ULN.
Albumin ≥ 3 g/dl.
Potassium ≥ lower limit of normal (LLN).
Serum total calcium (correct for serum albumin) or ionized calcium ≥ LLN.
Renal function as defined below:
Cardiac function as defined below:
All colony-forming growth factor(s) (i.e., filgrastim, sargramostim, or erythropoietin) must have been discontinued for at least 7 days prior to Day 1 or 14 days if PEG formulations were received.
An understanding, ability, and willingness to fully comply with study procedures and restrictions.
Subjects with Ommaya Reservoirs, VP shunts (nonmetallic) or similar will have a technical evaluation of the screening non-contrast CT scan of the head conducted by an Insightec trained technical Research and Development (R&D) specialist which will be provided to SonALAsense. This information will be included in the eligibility review by SonALAsense and designee. During mapping of the target area, if the machine determines that it cannot treat within the safety limits of the system (i.e., skull area, number of elements, etc.), the device will signal that it cannot initiate a sonication at that target and the investigator will determine whether to proceed with the treatment.
DMG Subjects:
Age ≥ 5 years old. Subjects younger than 5 years old may be eligible after discussion with the Sponsor Medical Monitor/designee.
Radiological diagnosis of Diffuse Midline Glioma (DMG) with tumor involving the pons (intrinsic, pontine based infiltrative lesion; hypointense on 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, cerebellum, and/or molecular confirmation of H3K27M mutation of pontine, thalamic, cerebellar glioma.
Subjects may be asked to agree to provide access to previously obtained biopsy results.
Prior treatment consisting of institutional standard of radiotherapy (including the combination with chemotherapy, by institutional standard) that was completed ≥ 4 weeks and ≤ 24 weeks prior to Day 1, and must have recovered from acute effects to CTCAE (version 5) Grade 1 or baseline prior to Day 1.
Subjects who recur/progressed after tumor resection are not excluded.
Must have stable to improved imaging by RAPNO/mRANO criteria comparing the scan obtained post radiotherapy to the scan obtained during the screening period. The comparison of diagnosis imaging scan and screening imaging scan must be reviewed by the study site's neuroradiologist and the principal investigator. If subjects present within 3 months after completion of radiotherapy and the comparison of the diagnosis scan to the screening scan is consistent with RAPNO/mRANO progression but pseudoprogression is a consideration, then the subject can be re-screened if the subject falls out of the screening window.
Subjects who are on steroids must be on a stable to decreasing dose of steroids prior to Day 1, with a maximum dexamethasone of 1 mg/m²/day, pediatric or adult population or by institutional standard.
Performance status assessed within 14 days of Day 1: Karnofsky (age ≥ 16 years) or Lansky (age < 16) score ≥ 50% allowing for stable neurological deficit due to DMG.
Subjects must have fully recovered from the acute toxic effects of all prior anti-cancer therapy prior to Day 1 and must meet the following minimum duration from prior anti- cancer directed therapy prior to enrollment.
• 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.
Subjects must have adequate organ and marrow function as defined below:
Absolute neutrophil count ≥ 1,000/mm³, without the use of myeloid growth factors (e.g., GCSF) within 7 days prior to Day 1.
Platelets ≥ 100,000/mm³ (unsupported, defined as no platelet transfusion within 7 days prior to Day 1).
Hemoglobin ≥ 8 g/dl maintained without the need for erythropoietin stimulating agents (may have received last transfusion within 7 days prior to Day 1).
Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN); in subjects with Gilbert syndrome, total bilirubin >1.5 ULN as long as direct bilirubin is normal.
ALT < 3 x institutional ULN.
AST < 3 x institutional ULN.
Albumin ≥ 3 g/dl.
Potassium ≥ lower limit of normal (LLN).
Serum total calcium (correct for serum albumin) or ionized calcium ≥ LLN.
Renal Function as defined below:
Cardiac Function as defined below:
All colony-forming growth factor(s) (i.e., filgrastim, sargramostim or erythropoietin) must have been discontinued for at least 7 days prior to Day 1 or 14 days if PEG formulations were received.
Subjects with Ommaya Reservoirs, VP shunts (nonmetallic) or similar will have a technical evaluation of the screening non-contrast CT scan of the head conducted by an Insightec trained technical R&D specialist which will be provided to SonALAsense. This information will be included in the eligibility review by SonALAsense and designee. During mapping of the target area, if the machine determines that it cannot treat within the safety limits of the system (i.e., skull area, number of elements, etc.), the device will signal that it cannot initiate a sonication at that target and the investigator will determine whether to proceed with the treatment.
Ability to provide written, signed, and dated (personally or via a legally authorized representative) informed consent/and assent at screening as applicable to participate in the study.
Exclusion criteria
DIPG Subjects:
DMG Subjects:
Primary purpose
Allocation
Interventional model
Masking
15 participants in 5 patient groups
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Patient Advocacy; Patient Advocacy
Data sourced from clinicaltrials.gov
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