Purpose

This study is looking to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of lyso-thermosensitive liposomal doxorubicin (LTLD) administered in combination with MR-HIFU in children with relapsed/refractory solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, and germ cell tumors.

Conditions

Eligibility

Eligible Ages
Under 30 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.
  • 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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part A
LTLD will be administered intravenously in combination with MR-HIFU ablation on day 1 of every 21 day cycle. There will be two potential dose escalation of LTLD with highest dose not to exceed the adult recommended MTD. Patients may receive up to a total of 6 cycles.
  • Device: Magnetic resonance high intensity focused ultrasound
    Magnetic resonance (MR)-high intensity focused ultrasound (HIFU) provides precise controlled delivery of heat by focusing ultrasound energy inside a lesion using an external applicator that is completely non-invasive and non-ionizing.
    Other names:
    • MR-HIFU
  • Drug: Lyso-thermosensitive liposomal doxorubicin
    A heat-activated formulation of liposomal doxorubicin with unique property of heat-activated release of doxorubicin, an active agent in most pediatric solid tumors.
    Other names:
    • LTLD; ThermoDox
Experimental
Part B
LTLD at dose determined from Part A will be administered intravenously on day 1 of every 21 day cycle. MR-HIFU induced MHT will follow immediately post LTLD infusion for one hour to target area with target temperatures of 40-45°C. Patients may receive up to a total of 6 cycles
  • Device: Magnetic resonance high intensity focused ultrasound
    Magnetic resonance (MR)-high intensity focused ultrasound (HIFU) provides precise controlled delivery of heat by focusing ultrasound energy inside a lesion using an external applicator that is completely non-invasive and non-ionizing.
    Other names:
    • MR-HIFU
  • Drug: Lyso-thermosensitive liposomal doxorubicin
    A heat-activated formulation of liposomal doxorubicin with unique property of heat-activated release of doxorubicin, an active agent in most pediatric solid tumors.
    Other names:
    • LTLD; ThermoDox

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington, District of Columbia 20010
Contact:
Ann Liew, MS, CCRP
202-476-6755
aliew@childrensnational.org

More Details

NCT ID
NCT02536183
Status
Recruiting
Sponsor
AeRang Kim

Study Contact

Ann Liew, MS, CCRP
202-476-6755
aliew@childrensnational.org

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.