MRI Sarcoma Non Invasive Thermometry

NCT ID: NCT00093509

Last Updated: 2014-09-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-11-30
• Study Completion Date: 2009-10-31

Brief 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.

Detailed 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.

Conditions

Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Magnetic Resonance Based Thermometry

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).

Group Type: EXPERIMENTAL

doxorubicin hydrochloride

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

hyperthermia treatment with an MRI Compatible Radiofrequency Extremity Hyperthermia Applicator

Intervention Type: PROCEDURE

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 therapy

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

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.

Intervention Type: RADIATION

Other Intervention Names

Adriamycin; Ifosfamide - Ifex; Mesna - sodium 2-mercapto-ethanesulphonate

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mark Dewhirst

OTHER

Sponsor Role: lead

Responsible Party

Mark Dewhirst

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ellen L. Jones, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke Cancer Institute

Zeljko Vujaskovic, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke Cancer Institute

Durham, North Carolina, United States

Countries

United States

References

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 patients treated for high grade extremity soft tissue sarcomas. Med Phys. 2009 Nov;36(11):4848-58. doi: 10.1118/1.3227506.

Reference Type: RESULT

PMID: 19994492 (View on PubMed)

Other Identifiers

DUMC-1308-04-7R5

Identifier Type: OTHER

Identifier Source: secondary_id

DUMC-G880018

Identifier Type: -

Identifier Source: secondary_id

CDR0000388048

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00008831

Identifier Type: -

Identifier Source: org_study_id