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

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)