MRI Sarcoma Non Invasive Thermometry

Mark Dewhirst

Status and phase: Completed; Phase 2; Phase 1

Conditions: Sarcoma

Treatments: Drug: doxorubicin hydrochloride; Procedure: hyperthermia treatment with an MRI Compatible Radiofrequency Extremity Hyperthermia Applicator; Drug: ifosfamide and mesna; Radiation: radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00093509

DUMC-G880018

DUMC-1308-04-7R5 (Other Identifier)

CDR0000388048 (Other Identifier)

Pro00008831

Details and patient eligibility

About

RATIONALE: Hyperthermia therapy kills tumor cells by heating them to several degrees above body temperature. Using MRI to measure heat may help to determine the effectiveness of hyperthermia therapy. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as ifosfamide and doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining hyperthermia with radiation therapy and chemotherapy before surgery may kill more tumor cells and shrink the tumor so that it can be removed.

PURPOSE: This phase I/II trial is studying the side effects of hyperthermia when given together with radiation therapy and optional chemotherapy and to see how well they work in treating patients who are undergoing surgery for soft tissue sarcoma of the limbs.

Full description

OBJECTIVES:

Primary

• Determine the feasibility and accuracy of real time magnetic resonance-based non-invasive thermometry in patients with grade 2 or 3 soft tissue sarcoma of the extremity receiving combination hyperthermia, radiotherapy, surgery, and optional high-dose ifosfamide and doxorubicin.

Secondary

• Determine the local control, disease-free survival, and overall survival of patients treated with this regimen.
• Determine acute and late toxic effects of this regimen in these patients.
• Correlate measurements of tumor physiology, defined by gadolinium-enhanced magnetic resonance imaging, magnetic resonance spectroscopy, and tumor oxygenation, with clinical and/or pathological response and/or metastatic potential in patients treated with this regimen.

OUTLINE: Patients may receive high-dose ifosfamide IV continuously over 6 days (144 hours). Beginning 3 weeks after the completion of ifosfamide, patients undergo radiotherapy once daily, 5 days a week, for 5 weeks. Beginning 1 hour after radiotherapy, patients also undergo hyperthermia (with heat measured by conventional and magnetic resonance-based thermometry) over 1-2 hours once weekly for 5 weeks. Approximately 4 weeks after the completion of radiotherapy and hyperthermia, patients undergo surgery. Approximately 1 month after surgery, patients may then receive high-dose doxorubicin IV once every 4 weeks for 4 courses.

PROJECTED ACCRUAL: A total of 10-30 patients will be accrued for this study within 2-6 years.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients will have histologically proven grade 2 or grade 3 soft tissue sarcoma.
• Karnofsky performance status ≥ 70.
• Life expectancy ≥ 6 months.
• There is no specific tumor size limitation, but the involved extremity must fit within the hyperthermia applicator.
• Patients must be ≥ 18 years of age.
• Patients who are to receive chemotherapy must have a left ventricular ejection fraction on resting MUGA scan of at least 45% to confirm adequate cardiac function
• Patients must competent to consent to be in the study and sign an approved informed consent.

Exclusion criteria

• Pregnant patients
• Patients with cardiac pacemakers and implanted defibrillators or other devices not compatible with ultrasound or microwave technology
• Patients who have any metal in their bodies including orthopedic rods, surgical clips, bullets, or shrapnel, etc. unless cleared by MRI staff and Hyperthermia physicians

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

15 participants in 1 patient group

Magnetic Resonance Based Thermometry

Experimental group

Description:

Patients will receive hyperthermia throughout the course of radiotherapy delivered once weekly for a total of 5 treatments. Each treatment will last 1-2 hours with a goal of delivering a cumulative thermal dose of 10-100 CEM 43˚T90. Interstitial temperature measurements will be taken by placing a single (less than or equal to) 15 gauge thermometry catheter into the tumor. In addition to hyperthermia treatment and radiation therapy all patients will receive conventional surgery for the removal of their tumors. Some patients will also receive chemotherapy if their treating physician thinks it is the their best interested (including the possibility of doxorubicin hydrochloride or ifosfamide and mesna).

Treatment:

Radiation: radiation therapy

Drug: ifosfamide and mesna

Procedure: hyperthermia treatment with an MRI Compatible Radiofrequency Extremity Hyperthermia Applicator

Drug: doxorubicin hydrochloride