Comparing the Effectiveness of Combined Hyperthermia and External Beam Radiation (EBRT) Versus EBRT Alone in Treating Patients With Painful Bone Metastases

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Shin Kong Wu Ho-Su Memorial Hospital
Sponsor:
Information provided by (Responsible Party):
Shin Kong Wu Ho-Su Memorial Hospital
ClinicalTrials.gov Identifier:
NCT01842048
First received: April 24, 2013
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

The main goals of deep hyperthermia combined with external beam radiation (EBRT) on bone metastases are the response on pain relief, duration of response and time to achieve complete pain relief.


Condition Intervention Phase
All Type of Cancers With Bony Metastasis
Other: Hyperthermia
Radiation: External-beam radiotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care

Resource links provided by NLM:


Further study details as provided by Shin Kong Wu Ho-Su Memorial Hospital:

Primary Outcome Measures:
  • Complete response rate [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Complete response rate defined with Brief Pain Inventory score of zero plus no concomitant increase analgesic intake within 3 months after radiotherapy.


Secondary Outcome Measures:
  • Adverse events [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Incidence of treatment-related adverse events from hyperthermia and RT.

  • Tumor response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To determine the difference of radiological tumor response in measurable indicated lesions on week 12.

  • Pain relief [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    To determine the difference in response of pain relief by Brief Pain Inventory score. To determine time and duration to pain relief on indicated lesion.

  • Quality-of-life [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    To compare the impact on quality-of-life using EORTC-C30 questionares.


Estimated Enrollment: 152
Study Start Date: July 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: External-beam radiotherapy combine hyperthermia
Hyperthermia 42℃ ± 0.5℃ for 40min, 2 times/week within 2hr after irradiation. Radiation protocol are 3Gy 5 times a week for a total of 30Gy/10fx/2 weeks
Other: Hyperthermia Radiation: External-beam radiotherapy
Active Comparator: External-beam radiotherapy alone
External-beam radiotherapy alone comprising 30Gy/10 fractions, 5 times a week, administered with 2 weeks.
Radiation: External-beam radiotherapy

Detailed Description:

The goal of this study is to conduct comparative data on the efficacy of low temperature (40-43℃ range) deep hyperthermia adding on external beam radiation for treatment of metastatic bone tumors. There are 3 reasons of conducting this clinical trial. Firstly, radiotherapy is most effective modality for bony metastases treatment, but only limited radiation dose can be delivered to metastatic bony metastatic sites with relatively short response duration observed clinically. Since it is a palliative treatment for pain relief, some patients develop recurrent pain at the same lesions a few months later. Most patients must accept their hopeless conditions and accept toward the end of their lives due to difficulty of reirradiation. There is urgently need for more effective treatment. Secondly, most combination of hyperthermia and radiation trials were relatively high dose of radiation, with the basic idea of hyperthermic radiosensitization, the combination of hyperthermia and radiotherapy on bone metastasis is warrant. Clinical trials experiences on relatively less deep tumors such as breast, head and neck cancers, extremity sarcoma or melanoma may not be applied on deep seated tumors. Bony metastases are usually deep seated lesions with hard cortex bone surrounded. The real benefit of hyperthermia can be highlighted on bony metastases. Thirdly, metastatic bony microenvironment are critical for the providing of bone marrow-derived immune suppressor cells circulating to systemic tumor microenvironment, mild thermal therapy to metastatic bony microenvironment may have dual immunomodulatory effects: direct enhancement of immune cell activity through thermally sensitive molecular pathways associated with immune cell function/activation, and, indirect enhancement of immunosurveillance through a reduction in hypoxia-induced immune suppressor cells around metastatic foci via improved tumor vascular perfusion. An unexpected survival benefit may demonstrated from this study.

Patients are stratified according to solitary or multiple sites, primary cancer type (Breast or prostate vs others), and severity of pain (i.e., worst pain score in the last 24-hour period) (4-6 vs 7-10). Patients are randomized to 1 of 2 treatment arms.

Treatment protocol A was designed to compare the response of matched tumors in the same patient treated by radiation alone or by radiation combined with hyperthermia when the patient had multiple tumors. Two tumors of comparable size were treated with either protocol A or B, and the responses were compared. The tumor size was computed as the product of maximum length times maximum width.

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or clinically confirmed solid tumor metastasis with index lesion involving or abutting bone. *Index lesion means an irradiated field covered lesions contoured from CT-Simulation which may generally less than 20cm, include 4-5 vertebra bodies, sacrum plus adjacent iliac lesions or a segment of femerol bone. Each patient can only have one index lesion for this study.
  • Index lesion with bone destruction either osteolytic or osteoblastic in nature as assessed on CT or MRI imaging
  • If the nature of the metastatic disease has been previously documented, the index lesion to be treated does not require further documentation (i.e., biopsy)
  • ≥ One primary painful metastatic site. The most painful site that need treatment first will be elected as index lesion site for evaluation of response. Additional less painful metastatic sites may be present. Patients who elect to have another course of RT treatment on different metastatic sites after the initial treatment are allowed.
  • Worst pain in the last 24 hours must be ≥ 4 on a 0-10 numeric scale.
  • Index lesion causing clinical or radiographic evidence of partial spinal cord or cauda equina compression/effacement is allowed.
  • Have developed pain or have persistent pain while on a stable chemotherapy, hormonal therapy, target therapy or bisphosphonate therapy regimen is allowed. There will be no change of chemotherapy, hormonal therapy, or bisphosphonate therapy for 4 weeks before and after radiotherapy
  • ECOG performance status 0-3
  • Life expectancy ≥ 3 months
  • Patients with impending fracture of weight bearing bone or patients with symptoms of spinal cord compression should have surgical opinion before the start of radiotherapy. Patient should not be able to be enrolled in this study if surgery is scheduled.

Exclusion Criteria:

  • Index lesion involves the skull
  • Index lesion has evidence of a pathologic fracture, impending fracture need immediate surgery are not eligible. Those patients had received decompression surgery are not eligible.
  • Has undergone prior radiotherapy at the index lesion
  • Those who chemotherapy or systemic treatment will be changed during study period.
  • Patients had history of metal implant inside or outside irradiation field are not eligible .
  • Patients had history of pacemaker insertion due to arrhythmia are not eligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01842048

Contacts
Contact: Kwan-Hwa Chi, M.D. 886-2-28332211 ext 2273 M006565@ms.skh.org.tw
Contact: Yu-Shan Wang, Ph.D 886-2-28332211 ext 2614 T006659@ms.skh.org.tw

Locations
Taiwan
Shin Kong Wu Ho-Su Memorial Hospital Recruiting
Taipei, Taiwan, 11101
Contact: Su-Chen Huang, M.S.    886-2-28332211 ext 2612    A007267@ms.skh.org.tw   
Principal Investigator: Kwan-Hwa Chi Chi, M.D.         
Sponsors and Collaborators
Shin Kong Wu Ho-Su Memorial Hospital
  More Information

No publications provided

Responsible Party: Shin Kong Wu Ho-Su Memorial Hospital
ClinicalTrials.gov Identifier: NCT01842048     History of Changes
Other Study ID Numbers: 20120305D
Study First Received: April 24, 2013
Last Updated: April 24, 2014
Health Authority: Taiwan: Department of Health

Keywords provided by Shin Kong Wu Ho-Su Memorial Hospital:
External-beam radiotherapy
Hyperthermia

Additional relevant MeSH terms:
Neoplasm Metastasis
Bone Neoplasms
Bone Marrow Diseases
Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Site
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on August 20, 2014