Cryoablation or External-Beam Radiation Therapy in Treating Patients With Painful Bone Metastases - Full Text View

Sponsors and Collaborators:	North Central Cancer Treatment Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00540969

Purpose

RATIONALE: Cryoablation kills cancer cells by freezing them. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. It is not yet known whether cryoablation is more effective than external-beam radiation therapy in treating painful bone metastases.

PURPOSE: This randomized phase III clinical trial is studying cryoablation to see how well it works compared with external-beam radiation therapy in treating patients with painful bone metastases.

Condition	Intervention	Phase
Kidney Cancer Melanoma (Skin) Metastatic Cancer Pain Unspecified Adult Solid Tumor, Protocol Specific	Procedure: cryosurgery Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Phase III Randomized Trial of Cryoablation vs. Radiation for the Palliation of Painful Bone Metastases

Resource links provided by NLM:

MedlinePlus related topics: Cancer Kidney Cancer Melanoma Radiation Therapy

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Comparison of pre- and post-treatment worst pain in 24 hours at week 6 as measured on the numeric 0 to 10 Brief Pain Inventory (BPI) scale [ Designated as safety issue: No ]

Secondary Outcome Measures:

Average difference in pre- and post-treatment average pain, pain relief, and pain interference scores at week 6 as measured with the BPI [ Designated as safety issue: No ]
Average difference in pre- and post-treatment physical (PCS-8) and mental (MCS-8) quality of life at week 6 as measured by the 2 subscales of the Short Form (SF)-8 [ Designated as safety issue: No ]
Average difference in pre- and post-treatment worst pain in 24 hours, average pain, pain relief, and pain interference scores at weeks 12, 24, and 36 as measured with the BPI [ Designated as safety issue: No ]
Average difference in pre- and post-treatment physical (PCS-8) and mental (MCS-8) quality of life at weeks 12, 24, and 36 as measured by the 2 subscales of the SF-8 [ Designated as safety issue: No ]
Comparison of the proportion of treated tumors with at least a two-point decrease in worst pain score at weeks 6, 12, 24, and 36 after cryoablation or radiotherapy (RT) [ Designated as safety issue: No ]
Comparison of the proportion of treated tumors with at least a two-point decrease in average pain score at weeks 6, 12, 24, and 36 after cryoablation or RT [ Designated as safety issue: No ]
Comparison of change in analgesic use at weeks 6, 12, 24, and 36 after cryoablation or RT [ Designated as safety issue: No ]
Comparison of time to maximal pain relief after cryoablation or RT [ Designated as safety issue: No ]
Comparison of time to recurrence of worst pain at or above baseline worst pain score in the 36-week follow-up period as measured on a numeric 0 to 10 scale [ Designated as safety issue: No ]
Incidence of treatment-related adverse events for cryoablation and RT [ Designated as safety issue: Yes ]

Estimated Enrollment:	140
Study Start Date:	February 2008
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I (percutaneous cryoablation): Experimental Cryoprobes are inserted percutaneously under CT scan or ultrasound guidance, to the malignant soft tissue-bone interface. Patients undergo ablations using a freeze-thaw-freeze cycle lasting approximately 10-5-10 minutes, respectively.	Procedure: cryosurgery Patients undergo cryosurgery using guidance from CT scan or ultrasound
Arm II (external-beam radiotherapy): Active Comparator Patients undergo external-beam radiotherapy comprising either a single 8 Gy dose or 20 Gy/5 fractions administered over 1 week.	Radiation: radiation therapy Patients undergo radiotherapy for 1 week

Detailed Description:

OBJECTIVES:

To determine pain relief in cancer patients with painful metastatic disease involving bone following treatment with cryoablation as compared to radiotherapy (RT).
To compare the impact on quality-of-life following cryoablation or RT in patients with painful metastatic disease as measured using the validated Brief Pain Inventory (BPI) and Short Form (SF)-8.
To determine change in analgesic use following therapy.
To determine the frequency and severity of complications following treatment of painful metastases involving bone with either cryoablation or RT.

OUTLINE: This is a multicenter study. Patients are stratified according to size of the indexing lesion (≤ 5 cm vs > 5 cm), location of the target lesion (pelvis vs extremity vs vertebral body vs other), primary cancer type (melanoma or renal cell carcinoma vs other), 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.

Arm I (percutaneous cryoablation): Cryoprobes are inserted percutaneously under CT scan or ultrasound guidance, to the malignant soft tissue-bone interface. Patients undergo ablations using a freeze-thaw-freeze cycle lasting approximately 10-5-10 minutes, respectively.
Arm II (external-beam radiotherapy): Patients undergo external-beam radiotherapy comprising either a single 8 Gy dose or 20 Gy/5 fractions administered over 1 week. Patients are contacted via phone on days 1 and 4 post treatment, weekly in weeks 1-4, every 2 weeks in weeks 6-24, and then every four weeks in weeks 28-36. Patients undergo pain and pain interference with daily life assessment at baseline and at these time points. Patients who elect to have repeated treatment (either radiotherapy or cryoablation) within the first 6 weeks after the initial treatment are removed from the study.

Patients who fail to achieve a 2-point reduction in worst or average pain (in a 24-hour period) during weeks 6-20 after initial treatment and patients who report a return of pain (i.e., pain ≥ the worst pain in a 24-hour period reported at baseline) for 2 consecutive time points are offered the alternative treatment (radiotherapy or cryoablation, whichever the patient was not randomized to receive at initial treatment)*.

NOTE: *Patients who refuse to receive the alternative treatment are taken off study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Inclusion criteria:

Histologically or cytologically confirmed solid tumor metastasis with index lesion involving or abutting bone
- Index lesion with bone destruction is predominantly osteolytic in nature as assessed on CT 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
- Additional less painful metastatic sites may be present
Worst pain in the last 24 hours must be ≥ 4 on a 0-10 numeric scale
Current analgesic therapies have failed OR the patient is experiencing intolerable side effects
Tumor is appropriate for radiotherapy as determined by the participating radiation oncologist and accessible for cryoablation as determined by the participating radiologists upon review of ultrasound, CT scan, X-ray, or MRI examinations
Have completed chemotherapy, hormonal therapy, or bisphosphonate therapy ≥ 4 weeks prior to registration OR have developed pain or have persistent pain while on a stable chemotherapy, hormonal therapy, or bisphosphonate therapy regimen for a period of ≥ 4 weeks

Exclusion criteria:

Index lesion causing clinical or radiographic evidence of spinal cord or cauda equina compression/effacement
Index lesion involves the skull
- Treatment of other painful lesions in patients with skull lesions is not excluded
Index lesion has evidence of a pathologic fracture or impending fracture in weight-bearing bones (e.g., vertebral body, periacetabular region, femur, or tibia) with > 50% loss of cortical bone

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 2 months
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

See Disease Characteristics
No concurrent medication known to interfere with platelet function or coagulation (e.g., aspirin, ibuprofen, clopidogrel, or warfarin) and such medications have been discontinued for an appropriate time period based on the drug half-life and known activity (e.g., aspirin for 7 days) for patients randomized to receive cryoablation only
Low molecular weight heparin preparations must be discontinued 8 hours prior to cryoablation
At least 2 weeks since prior cytotoxic chemotherapy (for patients randomized to receive cryoablation only)

Exclusion criteria:

Has undergone prior cryoablation or radiotherapy of the index lesion
Prior radiopharmaceutical therapy completed ≤ 4 weeks prior to registration
Initiation of new chemotherapy ≤ 4 weeks prior to registration
Concurrent surgery involving the treated lesion
Anticipated treatment of the index lesion that would require ice-ball formation within 0.5 cm of the spinal cord, brain, other critical nerve structure, large abdominal vessel such as the aorta or IVC, bowel, or bladder

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00540969

Locations

United States, Alabama
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Wisconsin
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226
Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Matthew R. Callstrom, MD, PhD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	North Central Cancer Treatment Group ( Charles L. Loprinzi )
Study ID Numbers:	CDR0000570788, NCCTG-N06C6
Study First Received:	October 5, 2007
Last Updated:	June 20, 2009
ClinicalTrials.gov Identifier:	NCT00540969 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

bone metastases
pain
unspecified adult solid tumor, protocol specific
stage IV melanoma
stage IV renal cell cancer

Study placed in the following topic categories:

Urinary Tract Neoplasm
Kidney Cancer
Pain
Urogenital Neoplasms
Urologic Neoplasms
Melanoma
Carcinoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Renal Cancer
Urologic Diseases

Kidney Neoplasms
Nevus, Pigmented
Neoplasms, Germ Cell and Embryonal
Neoplasm Metastasis
Carcinoma, Renal Cell
Neuroepithelioma
Nevus
Kidney Diseases
Adenocarcinoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Urogenital Neoplasms
Urologic Neoplasms
Neuroendocrine Tumors
Melanoma
Carcinoma
Neuroectodermal Tumors
Neoplastic Processes
Neoplasms
Pathologic Processes

Neoplasms by Site
Urologic Diseases
Kidney Neoplasms
Neoplasms, Germ Cell and Embryonal
Carcinoma, Renal Cell
Neoplasm Metastasis
Nevi and Melanomas
Kidney Diseases
Adenocarcinoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on August 28, 2009