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A Phase III Randomized Trial of Cryoablation vs. Radiation for the Palliation of Painful Bone Metastases

Phase 3
18 Years
Not Enrolling
Kidney Cancer, Melanoma (Skin), Metastatic Cancer, Pain, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase III Randomized Trial of Cryoablation vs. Radiation for the Palliation of Painful Bone Metastases


- 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,

- 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.

Inclusion Criteria


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

- Index lesion involves the skull

- Treatment of other painful lesions in patients with skull lesions is not

- 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


- ECOG performance status 0-2

- Life expectancy ≥ 2 months

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception


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

- Low molecular weight heparin preparations must be discontinued 8 hours prior to

- 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

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:


Principal Investigator

Matthew R. Callstrom, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Federal Government

Study ID:




Start Date:

February 2008

Completion Date:

Related Keywords:

  • Kidney Cancer
  • Melanoma (Skin)
  • Metastatic Cancer
  • Pain
  • Unspecified Adult Solid Tumor, Protocol Specific
  • bone metastases
  • pain
  • unspecified adult solid tumor, protocol specific
  • stage IV melanoma
  • stage IV renal cell cancer
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Melanoma
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Bone Neoplasms
  • Bone Marrow Diseases



Mayo Clinic ScottsdaleScottsdale, Arizona  85259
Mayo Clinic - JacksonvilleJacksonville, Florida  32224
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Medical College of Wisconsin Cancer CenterMilwaukee, Wisconsin  53226
Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical CenterMilwaukee, Wisconsin  53201-2901
UAB Comprehensive Cancer CenterBirmingham, Alabama  35294