A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors

Inclusion Criteria:

• AGE: ≥ 12 years of age.

• DIAGNOSIS: Histologically confirmed malignant solid tumors

• TUMOR LOCATION: Patient must have at least one tumor located in areas accessible toHIFU, which will be defined as the target lesion(s). Target lesions must bereachable within the normal safety margins of HIFU as specified in the instructionsfor use.

• TARGET LESION(S): Radiographically measurable/evaluable solid tumor targetlesion(s).

• THERAPEUTIC OPTIONS:

• Malignant Tumor: The patient's cancer must have relapsed after or failed torespond to frontline curative therapy and there must not be other potentiallycurative treatment options available.

• PRIOR THERAPY:

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

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

• Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancerdrugs must be at least 3 weeks prior to study entry (6 weeks for priornitrosoureas) Prior treatment with anthracyclines is allowed as long as totalcumulative dose is ≤ 450 mg/m2.

• Immunotherapy: The last dose of immunotherapy (monoclonal antibody or vaccine)must be at least 3 weeks prior to study entry.

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

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

• Stem Cell Transplantation. At least 42 days post-autologous stem celltransplant or at least 90 post-allogeneic transplant and recovered fromtoxicities without evidence of graft versus host disease and on stable doses ofimmunosuppressive medications if required.

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

• CONCURRENT THERAPIES:

• No other anti-cancer therapy (chemotherapy, biological therapy, radiationtherapy) is permitted.

• PERFORMANCE STATUS:

• Lansky/Karnofsky performance level ≥ 50% (See Appendix I).

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

• HEMATOLOGIC FUNCTION:

• Peripheral absolute neutrophil count (ANC) of ≥ 1000/µL.

• Platelet count ≥ 75,000/µL (transfusion independent (no transfusion within atleast 7 days prior to enrollment)).

• HEPATIC FUNCTION:

• Total bilirubin must be ≤ 1.5 times the upper limit of normal (ULN) for age andgender.

• SGPT (ALT) must be ≤ 3.0 times the upper limit of normal for age.

• RENAL FUNCTION: Serum creatinine ≤ ULN for age/sex OR a creatinine clearance ≥60mL/min/1.73 m2.

• CARDIAC FUNCTION: Adequate Cardiac Function with Ejection Fraction > 50% byechocardiogram.

Exclusion Criteria:

• Clinically significant unrelated systemic illness, such as serious infections,hepatic, renal or other organ dysfunction, which in the judgment of the Principal orAssociate Investigator would compromise the patient's ability to tolerate studyinterventions.

• Patients who are pregnant or breast-feeding are not eligible for this study due torisks of fetal and teratogenic adverse events seen in animal/human studies withdoxorubicin. Negative pregnancy tests must be obtained in girls who arepost-menarchal. Males or females of reproductive potential may not participateunless they have agreed to use an effective contraceptive method beginning at thesigning of informed consent and until at least 30 days after the last dose of studydrug. The definition of adequate contraception will be based on the judgment of theprincipal investigator or designated associate.

• Implant or prosthesis within the path of the HIFU beam.

• Target pathway <1 cm from nerve plexus, spinal canal, or bowel.

• Target lesion in the skull.

• Inability to undergo MRI and/or contraindication for MRI.

• Inability to tolerate stationary position during HIFU.

• Previous history of hypersensitivity to doxorubicin or its liposomal formulations.

• Patients currently receiving other anticancer agents.

• Patients currently receiving other investigational agents.