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

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ClinicalTrials.gov Identifier: NCT02536183
Recruitment Status : Recruiting
First Posted : August 31, 2015
Last Update Posted : November 19, 2018
Sponsor:
Information provided by (Responsible Party):
AeRang Kim, Children's Research Institute

Tracking Information
First Submitted Date  ICMJE August 13, 2015
First Posted Date  ICMJE August 31, 2015
Last Update Posted Date November 19, 2018
Study Start Date  ICMJE October 2016
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 27, 2015)
  • Maximum tolerated dose of LTLD [ Time Frame: 3 weeks ]
    To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of LTLD administered in combination with MR-HIFU ablation in children with relapsed/refractory solid tumors by examining blood samples collected from participants
  • Toxicity profile of LTLD [ Time Frame: up to 18 weeks ]
    To define and describe the toxicities of LTLD administered in combination with MR-HIFU as measured by reportable adverse events of participants as per the CTCAE v 4.0
  • Pharmacokinetics of LTLD [ Time Frame: 8 days ]
    Analyze blood samples of participants to characterize the pharmacokinetic properties of LTLD administered in combination with MR-HIFU
  • Feasibility of treatment [ Time Frame: up to 18 weeks ]
    To determine the feasibility of LTLD administered at the recommended dose in combination with MR-HIFU induced mild hyperthermia (MHT) as determined by patient outcomes and adverse events
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02536183 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2015)
  • Antitumor Activity of the Treatment [ Time Frame: up to 18 weeks ]
    To preliminarily determine the antitumor activity of LTLD with MR-HIFU within the confines of a phase 1 study by examining the response of target lesions using RECIST criteria v1.1
  • Social Impact of the Treatment on Participants [ Time Frame: up to 18 weeks ]
    To determine changes in symptoms and quality of life in children treated with LTLD and MR-HIFU by administering the Symptom Distress Scale and Peds QL v4.0 to participants
  • Determine the Changes in Pharmacodynamic Immune Markers in Participants [ Time Frame: 3 weeks ]
    To determine the changes in immune markers in children treated with LTLD and MR-HIFU by examining blood samples from participants
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors
Official Title  ICMJE A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin (LTLD, ThermoDox®) and Magnetic Resonance-Guided High Intensity Focused Ultrasound (MR-HIFU) for Relapsed or Refractory Solid Tumors in Children, Adolescents, and Young Adults
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pediatric Cancer
  • Solid Tumors
  • Rhabdomyosarcoma
  • Ewing Sarcoma
  • Soft Tissue Sarcomas
  • Osteosarcoma
  • Neuroblastoma
  • Wilms Tumor
  • Hepatic Tumor
  • Germ Cell Tumors
Intervention  ICMJE
  • 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 Name: 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 Name: LTLD; ThermoDox
Study Arms
  • 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.
    Interventions:
    • Device: Magnetic resonance high intensity focused ultrasound
    • Drug: Lyso-thermosensitive liposomal doxorubicin
  • 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
    Interventions:
    • Device: Magnetic resonance high intensity focused ultrasound
    • Drug: Lyso-thermosensitive liposomal doxorubicin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 27, 2015)
34
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date October 2020
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender
Sexes Eligible for Study: All
Ages up to 30 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Emily Stern, RN, BSN 202-476-2802 estern@childrensnational.org
Contact: Stephanie Forlenza saforlenza@childrensnational.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02536183
Other Study ID Numbers  ICMJE HIFU Thermodox
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party AeRang Kim, Children's Research Institute
Study Sponsor  ICMJE AeRang Kim
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: AeRang Kim, MD, PhD Children's Research Institute
PRS Account Children's Research Institute
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP