MR-guided High Intensity Focused Ultrasound (HIFU) on Pediatric Solid Tumors
MR-guided High Intensity Focused Ultrasound (HIFU) on Pediatric Solid Tumors
The purpose of this study is to determine if Magnetic Resonance guided High Intensity Focused
 Ultrasound ablative therapy is safe and feasible for children, adolescents, and young adults
 with refractory or relapsed 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.
Inclusion Criteria:

 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 > 16 years old must have a Karnofsky performance level ≥ 50%, and children ≤ 16
 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.

 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.