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

March 16, 2019 updated by: Theodore Laetsch
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.

Study Overview

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center/Children's Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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
50mg IV every 4 weeks
Other Names:
  • Doxil
Hyperthermia to 42C for 30 minutes every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
4 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Terminal half-life (T1/2) of Doxil when delivered with MR-HIFU hyperthermia
Time Frame: 48 hours following first dose
48 hours following first dose
Volume of distribution (L/m2) of Doxil when delivered with MR-HIFU hyperthermia
Time Frame: 48 hours following first dose
48 hours following first dose
Clearance (mL/min) of Doxil when delivered with MR-HIFU hyperthermia
Time Frame: 48 hours following first dose
48 hours following first dose
Adverse events associated with Doxil when administered in combination with MR-HIFU hyperthermia
Time Frame: 6 months
6 months
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
Through study completion, an average of 1 year
Tumor response to MR-HIFU with liposomal doxorubicin
Time Frame: 6 months
6 months
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
Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2016

Primary Completion (Actual)

March 16, 2019

Study Completion (Actual)

March 16, 2019

Study Registration Dates

First Submitted

September 21, 2015

First Submitted That Met QC Criteria

September 22, 2015

First Posted (Estimate)

September 23, 2015

Study Record Updates

Last Update Posted (Actual)

March 19, 2019

Last Update Submitted That Met QC Criteria

March 16, 2019

Last Verified

March 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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