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RhabdomyosarcomaPhase 1NCT02557854

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

A Phase 1 study testing Doxorubicin HCl liposomal injection and Philips Sonalleve MR-HIFU Hyperthermia in people with Rhabdomyosarcoma and Neuroblastoma, run by Theodore Laetsch at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 year to 40 years
Conditions the study is for
Rhabdomyosarcoma, Neuroblastoma, Sarcoma
What is being tested?
Doxorubicin HCl liposomal injection and Philips Sonalleve MR-HIFU Hyperthermia
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Dec 2016to 16 Mar 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 40 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UT Southwestern Medical Center/Children's Medical Center

    Dallas, Texas, 75390

Other trials in United States

About this study

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.

Being tested
Doxorubicin HCl liposomal injection, Philips Sonalleve MR-HIFU Hyperthermia
Medical subject headings
Rhabdomyosarcoma, Neuroblastoma, Sarcoma, Sarcoma, Ewing, Osteosarcoma, Desmoid Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Doxorubicin HCl liposomal injectionDrug

    Also called Doxil

    50mg IV every 4 weeks

  • Philips Sonalleve MR-HIFU HyperthermiaDevice

    Hyperthermia to 42C for 30 minutes every 4 weeks

Study groups in NCT02557854
Study groupRoleWhat they receive
Doxil + MR-HIFU HyperthermiaExperimentalLiposomal 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
Receives: Drug: Doxorubicin HCl liposomal injection; Device: Philips Sonalleve MR-HIFU Hyperthermia

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of dose limiting toxicities (DLTs) during cycle 1 of therapy with MR-HIFU hyperthermia directed liposomal doxorubicin

    Dose limiting toxicities are generally CTCAE v4.03 grade 3-5 toxicities with specific exceptions detailed in the protocol.

    Measured: 4 weeks

Secondary outcomes (7)

  1. Terminal half-life (T1/2) of Doxil when delivered with MR-HIFU hyperthermia

    Measured: 48 hours following first dose

  2. Volume of distribution (L/m2) of Doxil when delivered with MR-HIFU hyperthermia

    Measured: 48 hours following first dose

  3. Clearance (mL/min) of Doxil when delivered with MR-HIFU hyperthermia

    Measured: 48 hours following first dose

  4. Adverse events associated with Doxil when administered in combination with MR-HIFU hyperthermia

    Measured: 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

    Measured: Through study completion, an average of 1 year

  6. Tumor response to MR-HIFU with liposomal doxorubicin

    Measured: 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

    Measured: Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2015 (estimated)
  2. Study startDec 2016
  3. Primary completion16 Mar 2019
  4. Study completion16 Mar 2019

Why it stopped: Lack of enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02557854
Sponsor's protocol ID
UTSW-HIFU-001
Status last verified
Mar 2019
First submitted
21 Sep 2015
Last updated
19 Mar 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

    PubMed 31401903

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Doxorubicin HCl liposomal injection and Philips Sonalleve MR-HIFU Hyperthermia in people with Rhabdomyosarcoma and Neuroblastoma, run by Theodore Laetsch at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 19 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of dose limiting toxicities (DLTs) during cycle 1 of therapy with MR-HIFU hyperthermia directed liposomal doxorubicin (time frame: 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02557854, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2019.

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