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HIFU Hyperthermia With Liposomal Doxorubicin (DOXIL) for Relapsed or Refractory Pediatric and Young Adult Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02557854
Recruitment Status : Withdrawn (Lack of enrollment)
First Posted : September 23, 2015
Last Update Posted : March 19, 2019
Information provided by (Responsible Party):
Theodore Laetsch, University of Texas Southwestern Medical Center

Brief Summary:
The purpose of this study is to determine whether Doxil (liposomal doxorubicin) given prior to MR-HIFU Hyperthermia is safe for the treatment of pediatric and young adult patients with recurrent and refractory solid tumors.

Condition or disease Intervention/treatment Phase
Rhabdomyosarcoma Neuroblastoma Sarcoma Sarcoma, Ewing Osteosarcoma Desmoid Drug: Doxorubicin HCl liposomal injection Device: Philips Sonalleve MR-HIFU Hyperthermia Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Actual Study Start Date : December 2016
Actual Primary Completion Date : March 16, 2019
Actual Study Completion Date : March 16, 2019

Arm Intervention/treatment
Experimental: Doxil + MR-HIFU Hyperthermia
Liposomal doxorubicin (Doxil) 50mg IV every 4 weeks followed by Magnetic Resonance High Intensity Focused Ultrasound hyperthermia (MR-HIFU) with Philips Sonalleve System to 42C for 30 minutes every 4 weeks
Drug: Doxorubicin HCl liposomal injection
50mg IV every 4 weeks
Other Name: Doxil

Device: Philips Sonalleve MR-HIFU Hyperthermia
Hyperthermia to 42C for 30 minutes every 4 weeks

Primary Outcome Measures :
  1. Rate of dose limiting toxicities (DLTs) during cycle 1 of therapy with MR-HIFU hyperthermia directed liposomal doxorubicin [ Time Frame: 4 weeks ]
    Dose limiting toxicities are generally CTCAE v4.03 grade 3-5 toxicities with specific exceptions detailed in the protocol.

Secondary Outcome Measures :
  1. Terminal half-life (T1/2) of Doxil when delivered with MR-HIFU hyperthermia [ Time Frame: 48 hours following first dose ]
  2. Volume of distribution (L/m2) of Doxil when delivered with MR-HIFU hyperthermia [ Time Frame: 48 hours following first dose ]
  3. Clearance (mL/min) of Doxil when delivered with MR-HIFU hyperthermia [ Time Frame: 48 hours following first dose ]
  4. Adverse events associated with Doxil when administered in combination with MR-HIFU hyperthermia [ Time Frame: 6 months ]
  5. Percentage of patients with relapsed or refractory solid tumors treated with MR-HIFU hyperthermia and Doxil who demonstrate disease progression at a MR-HIFU treated lesion [ Time Frame: Through study completion, an average of 1 year ]
  6. Tumor response to MR-HIFU with liposomal doxorubicin [ Time Frame: 6 months ]
  7. Percentage of patients treated with MR-HIFU hyperthermia who are able to receive hyperthermia (41-45C) to greater than 75% of the predetermined treatment volume for greater than 75% of the planned treatment duration [ Time Frame: Day 1 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age 1-40 years
  • Histologically confirmed malignant extra-cranial solid tumor or demoid fibromatosis
  • The subject's tumor must have relapsed after or failed to respond to frontline therapy and there must be no other known curative therapies available. Patients with desmoid fibromatosis must have relapsed after or failed to respond to at least one prior line of therapy, and in the opinion of the treating physician surgical resection of the tumor must not be possible without an amputation or other surgery predicted to result in an unacceptable functional deficit.
  • Subject must have a life expectancy of > 8 weeks
  • Karnofsky performance status > 50% for patients >16 years of age, or Lansky performance status > 50% for patients < 16 years of age.
  • The subject must have at least 1 measurable target lesion >10mm in longest dimension that is in an anatomic location treatable by MR-HIFU. Note that for this study, lesions in bone WILL be considered measurable provided they meet the other criteria by RECIST and are confirmed to be metabolically active on baseline studies by either MIBG uptake (for neuroblastomas) or PET avidity. Target lesions should be located so that they can be adequately heated by a hyperthermia treatment cell with a diameter of up to 58 mm, centered at a depth of 35 to 80 mm from the skin. There should be no staples, implants, extensive scarring, or other highly ultrasound absorbing or reflecting tissue in the expected beam path. For the first 5 patients enrolled on this study only, the lesion must be located in the extremities or pelvis to be considered treatable by MR-HIFU.
  • The subject must have recovered from the acute toxic effects of all prior therapy with the exception of alopecia. The following time must have elapsed from the last dose of the following medications to study enrollment:

    • myelosuppressive chemotherapy 14 days
    • hematopoetic growth factors 7 days (14 days for Neulasta)
    • biologic agent 7 days
    • monoclonal antibody 3 half-lives
    • immunotherapy (ie tumor vaccines) 42 days
    • palliative small port XRT 14 days
    • substantial bone marrow XRT 6 weeks
    • stem cell transplant or infusion without TBI 12 weeks
    • total body irradiation (TBI) 24 weeks
  • Adequate organ and marrow function as defined below:

    • absolute neutrophil count ≥ 1,000/mcL
    • platelets ≥ 75,000/mcl (without transfusion for 7 days)
    • hemoglobin > 8g/dL (may receive transfusions)
    • total bilirubin < 1.5 mg/dL
    • ALT(SPGT) < 225 U/L (45 U/L defined as ULN)
    • creatinine clearance or radioisotope GFR > 70 mL/min/1.73m2 OR a serum creatinine (mg/dL) less than or equal to the following:
    • Age (yrs)-----Male (mg/dL)-----Female (mg/dL)
    • 1-1.99----------0.6------------------0.6
    • 2-5.99----------0.8------------------0.8
    • 6-9.99----------1--------------------1
    • 10-12.99------1.2------------------1.2
    • 13-15.99------1.5------------------1.4
    • >16-------------1.7------------------1.4
  • Adequate cardiac function defined as an ejection fraction > 50% or shortening fraction > 27%
  • Cumulative lifetime anthracycline dose of < 450mg/m2
  • Females and males of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A male of child-bearing potential is any male (regardless of sexual orientation, having undergone a vasectomy, or remaining celibate by choice) who has attained Tanner stage III or greater sexual development. A female of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

    • Has not undergone a hysterectomy or bilateral oophorectomy; or
    • Has undergone menarche OR is > 13 years of age
  • Females of child-bearing potential must have a negative serum pregnancy test within 7 days of treatment.
  • Signed written informed consent must be obtained prior to any study procedures.

Exclusion Criteria:

  • Subjects may not be receiving any other investigational agents or anticancer therapies.
  • Subjects with known active brain metastases will be excluded from this clinical trial. Patients with brain metastases that have been treated and stable for > 30 days following treatment will be eligible.
  • Subjects who have received prior Doxil and progressed on this therapy are not eligible, but subjects may have received prior doxorubicin.
  • Subjects with a history of tumor progression within 30 days of anthracycline administration are not eligible. However, subjects who have previously received an anthracycline and subsequently relapse greater than 30 days after their most recent prior dose of anthracycline will be eligible.
  • History of allergic reactions attributed to doxorubicin or Doxil
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
  • Subjects with a contraindication to MR-HIFU
  • Subjects with conditions that carry high anesthetic risk in the opinion of the treating anesthesiologist are not eligible (i.e. subjects with significant airway compression by tumor or craniofacial abnormalities)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02557854

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United States, Texas
UT Southwestern Medical Center/Children's Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Theodore Laetsch
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Theodore Laetsch, Assistant Professor of Pediatrics, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT02557854    
Other Study ID Numbers: UTSW-HIFU-001
First Posted: September 23, 2015    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Sarcoma, Ewing
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Muscle Tissue
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action