Clinical trial NCT00211237: CAFE Study - Cancer Patient Fracture Evaluation
Official title: A Multicenter, Prospective, Randomized, Controlled Study to Compare Balloon Kyphoplasty to Non-surgical Fracture Management in the Treatment of Painful, Acute Vertebral Body Compression Fractures in Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cancer
Spinal Fractures
Keywords: Balloon Kyphoplasty
Cancer
Vertebral Compression Fracture
Back Pain
Spine
Lead sponsor: Medtronic Spinal and Biologics
Sponsor class: INDUSTRY
First posted: 2005-09-21
Enrollment: 134
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety and effectiveness of balloon kyphoplasty treatment for painful, acute, vertebral compression fractures (VCFs) as compared to standard non-surgical therapy in patients with cancer.

Detailed description: 1. STUDY OBJECTIVES AND ENDPOINTS

1.1. Objectives

The primary objective of this study is to evaluate the safety and effectiveness of balloon kyphoplasty treatment for painful, acute, VCFs as compared to standard non-surgical therapy in patients with cancer.

1.2. Primary Endpoint

The primary endpoint of the study is the improvement in functional status, as measured by the Roland-Morris Disability Questionnaire (RDQ) at 1 month. The primary hypothesis of the study is that the mean improvement will be larger in subjects initially assigned to management with balloon kyphoplasty. Note that all subjects will undergo 12 months of follow-up after initial treatment assignment.

1.3. Secondary Endpoints

The following secondary endpoints will also be examined. Comparisons will be made at each follow-up visit.

Safety:

* Rate of study treatment-related adverse events
* Change in neurological status

Clinical:

* Change in functional status as assessed with Karnofsky Performance Scale
* Change in quality of life as assessed by the SF-36v2™ Health Survey
* Change in back pain, as measured by a 10-point Numerical Rating Scale (NRS)
* Change in back-pain analgesics used
* Change in ambulation status
* Changes in activities of daily living
* Time to treatment failure

Radiographic:

* Change in spinal deformity, defined as the degree of spine angulation as assessed by an independent radiologist at the core laboratory
* Rate of subsequent vertebral body fractures, as assessed by independent radiologists at the core lab

In each case, the study hypothesis is that treatment with balloon kyphoplasty will result in an improvement in clinical or radiographic outcomes compared to baseline and compared to non-surgical treatment, with a preservation of outcomes in long-term follow-up.

Eligibility criteria: Inclusion Criteria:

1. One to 3 painful (pain on palpation/percussion over fractured vertebral body) VCF(s), T5-L5, with either bone marrow edema imaged by magnetic resonance imaging (MRI) or a fracture imaged by plain radiographs using the method of Genant
2. Pain NRS score ≥4 on a scale of 0 to 10

   * When the patient is newly diagnosed with multiple myeloma, the pain assessment must not be done until after completion of at least one pulse of steroid therapy or one week after the initiation of active multiple myeloma therapy.
3. Roland Morris Disability Questionnaire score ≥ 10 on a scale of 0 to 24
4. Patients must be at least 21 years old.
5. No change in chemotherapy regimen (change in dose(s) permitted) for 1 month prior to enrollment
6. No change in chemotherapy regimen (change in dose(s) permitted) planned for at least 1 month following enrollment
7. No major surgery to the spine planned for at least 1 month following enrollment
8. Life expectancy of ≥ 3 months
9. Patient has sufficient mental capacity to comply with the protocol requirements
10. Patient has stated availability for all study visits
11. Patient is able to understand the risks and benefits of participating in the study and is willing to provide written informed consent.

Exclusion Criteria:

1. Patients with primary tumors of the bone (e.g., osteosarcoma) or solitary plasmacytoma at site of the index VCF. Patients with these tumors in anatomic sites other than the index VCF are eligible.
2. Concurrent Phase I investigational anti-cancer treatment
3. Significant clinical morbidities (aside from the index fracture(s) and cancer) that may potentially interfere with the collection of data concerning pain and function
4. VCF morphology deemed unsuitable for balloon kyphoplasty
5. Additional non-kyphoplasty surgical treatment is required for the index fracture
6. Patients requiring the use of high-dose steroid (≥ 100 mg prednisone or 20 mg dexamethasone per day), intravenous (IV) pain medication, or nerve block to control chronic back pain unrelated to index VCF(s). Patients who receive high-dose steroids for treatment of their cancer (for at least 30 days) are eligible.
7. Patients with a platelet count of \< 20,000 measured at the time of hospital admission for the procedure
8. Spinal cord compression or canal compromise requiring decompression
9. Patients with osteoblastic tumors at the site of index VCF. Patients with osteoblastic tumors outside of vertebral levels intended for kyphoplasty may be enrolled.
10. Medical/surgical conditions contrary to the balloon kyphoplasty procedure (e.g., in the presence of active or incompletely treated local infection)
11. Known allergy to bone cement or contrast medium used in the treatment of study subjects
12. MRI contraindication (e.g., cerebral aneurysm clips, pacemaker, implanted biostimulators, cochlear implants, penile prosthesis)
13. Positive baseline pregnancy test (for women of child-bearing potential)
14. Patients who may require allogeneic bone marrow transplantation during the course of the study.

Other Reasons for Lack of Enrollment:

A. Patient is afraid to have surgery

B. Patient is afraid to have anesthesia

C. Patient/family is not willing to participate in research

D. Patient is not willing to be randomized

Primary outcomes:
measure: The Functional Status, as Measured by the Roland-Morris Disability Questionnaire (RDQ) at 1 Month
timeFrame: Baseline and 1 Month
Secondary outcomes:
measure: Change in Roland-Morris Disability Questionnaire Score
timeFrame: Baseline, 1 month, 3 months, 6 months, and 12 months
measure: Change in Functional Status Assessed With the Karnofsky Performance Scale
timeFrame: Baseline and 1 month
measure: Change in Functional Status Assessed With the Karnofsky Performance Scale
timeFrame: Baseline, 1 month, 3 months, 6 months, and 12 months
measure: Change in Back Pain
timeFrame: Baseline and 1 month
measure: Change in Back Pain
timeFrame: Baseline, 1 month, 3 months, 6 months, and 12 months
measure: Change in Quality of Life.
timeFrame: Baseline and 1 month
measure: Change in Quality of Life
timeFrame: Baseline, 1 month, 3 months, 6 months, and 12 months
measure: Change in Activities of Daily Living - Activities Reduced Due to Back Pain in Previous 2 Weeks
timeFrame: Baseline and 1 month
measure: Change in Activities of Daily Living - Activities Reduced Due to Back Pain in Previous 2 Weeks
timeFrame: Baseline, 1 month, 3 months, 6 months, and 12 months
measure: Change in Activities of Daily Living - Number of Days With Reduced Activities Due to Back Pain in Previous 2 Weeks
timeFrame: Baseline and 1 month
measure: Change in Activities of Daily Living - Number of Days With Reduced Activities Due to Back Pain in Previous 2 Weeks
timeFrame: Baseline, 1 month, 3 months, 6 months, and 12 months
measure: Change in Activities of Daily Living - Number of Days in Bed Due to Back Pain in Previous 2 Weeks
timeFrame: Baseline and 1 month
measure: Change in Activities of Daily Living - Number of Days in Bed Due to Back Pain in Previous 2 Weeks
timeFrame: Baseline, 1 month, 3 months, 6 months, and 12 months
measure: Ambulatory Status Change From Baseline to One Month
timeFrame: 1 month
measure: Ambulatory Status Change
timeFrame: Baseline, 7 days, 1 month, 3 months, 6 months, and 12 months
measure: Index Spinal Deformity Change Measured by Index Vertebral Body Angles From Baseline to 1 Month
timeFrame: Baseline and 1 month
measure: Index Spinal Deformity Change Measured by Index Vertebral Body Angles
timeFrame: Baseline, post-operation, 1 month, and 12 months
measure: Index Spinal Deformity Change Measured by Index Vertebral Body Height Ratio
timeFrame: Baseline and 1 month
measure: Index Spinal Deformity Change Measured by Index Vertebral Body Height Ratio
timeFrame: Baseline, post-operation, 1 month, and 12 months
measure: Back Pain Analgesics Used
timeFrame: Baseline, 7 days, and 1 month
measure: Back Pain Analgesics Used
timeFrame: Baseline, 7 days, 1 month, 3 months, 6 months, and 12 months
measure: Change in Neurology Status From Baseline (Motor Strength)
timeFrame: 1 month
measure: Change in Neurology Status From Baseline (Motor Strength)-Per Protocol
timeFrame: 1 month, 3 months, 6 months, and 12 months
measure: Change in Neurological Status From Baseline (Sensory Examination)
timeFrame: 1 month
measure: Change in Neurological Status From Baseline (Sensory Examination)
timeFrame: 1 months, 3 months, 6 months, and 12 months
measure: Change in Neurological Status From Baseline (Reflex Strength)
timeFrame: 1 month
measure: Change in Neurological Status From Baseline (Reflex Strength)
timeFrame: 1 months, 3 months, 6 months, and 12 months
measure: Change in Neurological Status From Baseline (Limb Strength)
timeFrame: 1 month
measure: Change in Neurological Status From Baseline (Limb Strength)
timeFrame: 1 months, 3 months, 6 months, and 12 months
measure: Rate of Study Treatment-related Adverse Events Within 30 Days of Baseline
timeFrame: 1 month
measure: Rate of Study Treatment-related Adverse Events Till Study Completion
timeFrame: 12 months
measure: Rate of Subsequent Vertebral Body Fractures
timeFrame: 1 month
measure: Rate of Subsequent Vertebral Body Fractures
timeFrame: 1 month and 12 months
Other outcomes:
Locations:
city: Escondido
country: United States
facility: Valley Radiology Inc., UCSD
state: California
city: Boulder
country: United States
facility: Boulder Neurosurgical Associates
state: Colorado
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Chevy Chase
country: United States
facility: Sibley Memorial Hospital
state: Maryland
city: Silver Spring
country: United States
facility: Greater Oncology Associates
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Calgary
country: Canada
facility: Foothills Hospital
state: Alberta
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: Berlin
country: Germany
facility: Charité Virchow-Klinikum
city: Hannover
country: Germany
facility: Medizinische Hochschule
city: Budapest
country: Hungary
facility: National Center for Spinal Disorders
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: London
country: United Kingdom
facility: Royal London
Study officials:
affiliation: Institute for Myeloma & Bone Cancer Research
name: James Berenson, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: H. Lee Moffitt Cancer Center
name: Frank Vrionis, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berenson J, Pflugmacher R, Jarzem P, Zonder J, Schechtman K, Tillman JB, Bastian L, Ashraf T, Vrionis F; Cancer Patient Fracture Evaluation (CAFE) Investigators. Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial. Lancet Oncol. 2011 Mar;12(3):225-35. doi: 10.1016/S1470-2045(11)70008-0. Epub 2011 Feb 16.