MR-guided High Intensity Focused Ultrasound (HIFU) on Pediatric Solid Tumors

Magnetic Resonance (MR)-guided high intensity focused ultrasound (HIFU) is an innovative
technique that allows for non-invasive thermal ablation of tissue. Advantages over
conventional local tumor control such as surgery, radiation, or radiofrequency are that
MR-HIFU is completely non-invasive, non-ionizing, and enables ablation of large tumor volumes
with avoidance of adjacent tissue injury. This study will evaluate the safety and feasibility
of MR-HIFU ablative therapy in children, adolescents, and young adults with refractory or
relapsed solid tumors that are located in bone or soft tissue in close proximity to bone.
Patients ≤ 30 years of age with refractory or relapsed solid tumors with measurable target
lesions that are located in bone or soft tissue in close proximity to bone are eligible.
Tolerability will be defined during the 14 days following MR-HIFU ablation. Patients will
continue to be followed for tumor response and secondary outcomes for up to one year post
ablation treatment.

AGE: ≤ 30 years of age.

DIAGNOSIS:

Histologically confirmed malignant 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, germ cell tumors, and desmoid
tumors.

TUMOR LOCATION: Target lesion(s) must be located in bone or soft tissue in close proximity
to bone. Target lesions must be reachable within the normal safety margins of HIFU as
specified in the instructions for use.

TARGET LESION(S): Radiographically evaluable or measurable solid tumor target lesion(s).

THERAPEUTIC OPTIONS:

Malignant Tumor: The patient's cancer must have relapsed after or failed to respond to
frontline curative therapy and there must not be other potentially curative treatment
options available. Curative therapy may include surgery, radiation therapy, chemotherapy,
or any combination of these modalities.

PRIOR THERAPY:

Patients must have fully recovered from the acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering on this study.

No limitation on the number of prior chemotherapy regimens that the patient may have
received prior to study entry.

Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must
be at least 3 weeks prior to study entry.

Immunotherapy: The last dose of immunotherapy (monoclonal antibody or vaccine) must be at
least 4 weeks prior to study entry.

Biologic (anti-cancer agent): The last dose of all biologic agents for the treatment of the
patient's cancer (such as retinoids or tyrosine kinase inhibitors) must be at least 7 days
prior to study entry.

Radiation therapy: The last dose of radiation to more than 25 % of marrow containing bones
(pelvis, spine, skull) must be at least 4 weeks prior to study entry. The last dose of all
other local palliative (limited port) radiation must be at least 2 weeks prior to study
entry.

Stem Cell Transplantation. At least 2 months post-autologous stem cell transplant or at
least 3 months post-allogeneic transplant and recovered from toxicities without evidence of
graft versus host disease and on stable doses of immunosuppressive medications if required.

Growth Factors. The last dose of colony stimulating factors, such as filgrastim,
sargramostim, and erythropoietin, must be at least 1 week prior to study entry, the last
dose of long-acting colony stimulating factors, such as pegfilgrastim, must be at least 2
weeks prior to study entry.

CONCURRENT THERAPIES:

No other anti-cancer therapy (chemotherapy, biological therapy, radiation therapy) is
permitted during HIFU treatment and post treatment follow up for tolerability (see section
3.3).

PERFORMANCE STATUS:

Patients > 10 years old must have a Karnofsky performance level ≥ 50%, and children ≤ 10
years old must have a Lansky performance level ≥ 50% (See Appendix I).

Patients who are unable to walk because of paralysis or motor weakness, but who are up in a
wheelchair will be considered ambulatory for the purpose of calculating the performance
score.

- HEMATOLOGIC FUNCTION:

1. Peripheral absolute neutrophil count (ANC) of ≥750/µL

2. Platelet count ≥75,000/µL (may receive transfusions)

- RENAL FUNCTION: Age-adjusted normal serum creatinine OR a creatinine clearance ≥60
mL/min/1.73 m2.

- ADEQUATE PULMONARY FUNCTION: Defined as no dyspnea at rest, and a pulse oximetry >94%
on room air if there is clinical indication for determination.

- Normal PT, PTT and INR < 1.5 x ULN (including patients on prophylactic
anticoagulation)

Exclusion Criteria:

Clinically significant unrelated systemic illness, such as serious infections, hepatic,
renal or other organ dysfunction, which in the judgment of the Principal or Associate
Investigator would compromise the patient's ability to tolerate the general anesthetic
required for the procedure.

Target lesions that are pulmonary primary tumors or metastases.

Implant or prosthesis or scar tissue within the path of the HIFU beam.

Target <1 cm from nerve plexus, spinal canal, bladder, bowel

Target in contact with hollow viscera

Lesion in the skull

Inability to undergo MRI and/or contraindication for MRI

Inability to tolerate stationary position during HIFU

Patients currently receiving other anticancer agents.

Patients currently receiving other investigational agents.