A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors

This is phase 1 trial of LTLD with MR-HIFU induced heating in children and young adults with
relapsed/refractory solid tumors.

Part A of the trial will be a traditional dose escalation study to determine the pediatric
MTD/RP2D of LTLD combined with MR-HIFU ablation which allows for release of doxorubicin in
the ablation zone and peri-ablation margins.

Part B of the trial will combine LTLD at the MTD/RP2D with MR-HIFU induced mild hyperthermia
(MHT) in an expanded cohort.

Inclusion Criteria:

- Part A: ≤21 years of age

- Part B: ≤ 30 years of age.

- Histologically confirmed malignant solid tumor.

- Patient must have at least one tumor located in areas accessible to HIFU, which will
be defined as the target lesion(s).

- Radiographically evaluable or measurable solid tumor target lesion(s).

- Malignant tumor that is relapsed or refractory and with no other potentially curative
treatment options available.

- Must have completed an appropriate washout period from prior therapy.

- Karnofsky or Lansky performance level ≥ 50%.

- Must have appropriate hematologic, hepatic and renal function.

- Adequate cardiac function with ejection fraction > 50%

Exclusion Criteria:

- Clinically significant unrelated systemic illness.

- Patients who are pregnant or breast-feeding.

- Target lesions that are pulmonary primary tumors or metastases.

- Implant or prosthesis or scar tissue within the path of the HIFU beam.

- Target lesion <1 cm from nerve plexus, spinal canal, and bowel.

- Lesion in the skull.

- Inability to undergo MRI and/or contraindication for MRI.

- Inability to tolerate stationary position during HIFU.

- Previous history of hypersensitivity to doxorubicin or its liposomal formulations.