MRI Sarcoma Non Invasive Thermometry

Sarcoma Clinical Trial

Official title:

Magnetic Resonance Based Non-Invasive Thermometry for Hyperthermic Treatment of Extremity Soft Tissue Sarcomas: A Multimodal Phase I/II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00093509
• Other study ID #: Pro00008831
• Secondary ID: DUMC-1308-04-7R5
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 6, 2004
• Last updated: August 29, 2014
• Start date: November 1999
• Est. completion date: October 2009

Study information

• Verified date: August 2014
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: October 2009
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma

Intervention

Drug:
• doxorubicin hydrochloride
To be dosed at 75 mg/m2 i.v. push every 4 weeks for 4 cycles. This treatment is optional and will not be used on all subjects.
• ifosfamide and mesna
2 gm / m2 ifosfamide mixed in 1000 cc D5W infused continuously over 24 hours daily for 6 days (144 hours); total ifosfamide dose 12 gm/ m2. For the day infusion only MESNA (sodium 2-mercapto-ethanesulphonate) is mixed with ifosfamide as above and given at 2.5 gm / m2 / 24 hours.

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

Radiation:
• radiation therapy
External beam megavoltage (= 4 MV) beams will be used at SSD, SAD = 70 cm at a dose rate of > 100 cGy/min. Fraction sizes of 180 cGy will be used 5 times per weeks in a continuous course. Total dose will be 45 Gy + 10%, consistent with sites being treated.

Locations

Country	Name	City	State
United States	Duke Cancer Institute	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Mark Dewhirst	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Craciunescu OI, Stauffer PR, Soher BJ, Wyatt CR, Arabe O, Maccarini P, Das SK, Cheng KS, Wong TZ, Jones EL, Dewhirst MW, Vujaskovic Z, MacFall JR. Accuracy of real time noninvasive temperature measurements using magnetic resonance thermal imaging in patie — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Temperature Rise from Baseline	MR-based thermometry measures: We are assessing agreement between the non-invasive MR measurements versus the invasive interstitial point measurements. The equivalence of median temperature measured within one or more MR ROI's (regions-of-interest in the MR image) and temperatures measured invasively in tissue immediately adjacent to those ROI's;	1 hour	No
Secondary	Overall Survival		every 6 months for up to 5 years	No