CAFE Study - Cancer Patient Fracture Evaluation

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Cancer, Spinal Fractures

Intervention / Treatment
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* Device: Balloon Kyphoplasty
* Other: Non Surgical Management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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. Roland Morris Disability Questionnaire score ≥ 10 on a scale of 0 to 24 Patients must be at least 21 years old. No change in chemotherapy regimen (change in dose(s) permitted) for 1 month prior to enrollment No change in chemotherapy regimen (change in dose(s) permitted) planned for at least 1 month following enrollment No major surgery to the spine planned for at least 1 month following enrollment Life expectancy of ≥ 3 months Patient has sufficient mental capacity to comply with the protocol requirements Patient has stated availability for all study visits Patient is able to understand the risks and benefits of participating in the study and is willing to provide written informed consent. Exclusion Criteria: 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. Concurrent Phase I investigational anti-cancer treatment Significant clinical morbidities (aside from the index fracture(s) and cancer) that may potentially interfere with the collection of data concerning pain and function VCF morphology deemed unsuitable for balloon kyphoplasty Additional non-kyphoplasty surgical treatment is required for the index fracture 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. Patients with a platelet count of < 20,000 measured at the time of hospital admission for the procedure Spinal cord compression or canal compromise requiring decompression Patients with osteoblastic tumors at the site of index VCF. Patients with osteoblastic tumors outside of vertebral levels intended for kyphoplasty may be enrolled. Medical/surgical conditions contrary to the balloon kyphoplasty procedure (e.g., in the presence of active or incompletely treated local infection) Known allergy to bone cement or contrast medium used in the treatment of study subjects MRI contraindication (e.g., cerebral aneurysm clips, pacemaker, implanted biostimulators, cochlear implants, penile prosthesis) Positive baseline pregnancy test (for women of child-bearing potential) 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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Balloon Kyphoplasty (BKP)<br>The subjects assigned to this group will undergo the treatment with Balloon kyphoplasty for their painful VCFs. | Device: Balloon Kyphoplasty<br>* Ballon Kyphoplasty is a minimally invasive technique aimed at reduction of VCFs using KyphX® Inflatable Bone Tamps followed by fracture fixation with KyphX® HV-R™ Bone Cement.<br>* Other names: KyphX Inflatable Bone Tamps;|
| Active Comparator: Non Surgical Management<br>The subjects in this group will undergo the non-operative treatments aimed at alleviation of back pain and restoration of decreased function associated with VCFs. | Other: Non Surgical Management<br>* Non-surgical treatment includes, but is not limited to, the following: back brace, pain medication, physical therapy, walking aids, bed rest, and radiation treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Functional Status, as Measured by the Roland-Morris Disability Questionnaire (RDQ) at 1 Month | The full scale name is the Roland-Morris Disability Questionnaire; it is a validated measure of physical disability due to back pain. The best score is 0 (no disability) and worst is 24 (maximum disability) | Baseline and 1 Month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Roland-Morris Disability Questionnaire Score | Roland-Morris Disability Questionnaire (RMDQ) was used to assess the physical disability due to back pain. The best score is 0 (no disability) and worst is 24 (maximum disability). | Baseline, 1 month, 3 months, 6 months, and 12 months | 
| Change in Functional Status Assessed With the Karnofsky Performance Scale | The Karnofsky Performance Scale rates a patient on an 11-step scale from 0 (dead) to 100 (normal, no complaints, no evidence of disease). | Baseline and 1 month | 
| Change in Functional Status Assessed With the Karnofsky Performance Scale | The Karnofsky Performance Scale rates a patient on an 11-step scale from 0 (dead) to 100 (normal, no complaints, no evidence of disease). | Baseline, 1 month, 3 months, 6 months, and 12 months | 
| Change in Back Pain | Back pain was assessed on a 10-point Numerical Rating Scale (NRS) from 0 (no pain) to 10 (worst possible pain). | Baseline and 1 month | 
| Change in Back Pain | Back pain was assessed on a NRS from 0 (no pain) to 10 (worst possible pain). | Baseline, 1 month, 3 months, 6 months, and 12 months | 
| Change in Quality of Life. | The SF-36 was used to assess quality of life. The SF-36 results were summarized into two components, a physical component summary score (PCS) (0-100) and a mental component summary score (MCS) (0-100). The higher the score, the better the quality of life. | Baseline and 1 month | 
| Change in Quality of Life | The SF-36 were used to assess quality of life. The SF-36 results were summarized into two components, a physical component summary score (PCS) (0-100) and a mental component summary score (MCS) (0-100). The higher the score, the better the quality of life. | Baseline, 1 month, 3 months, 6 months, and 12 months | 
| Change in Activities of Daily Living - Activities Reduced Due to Back Pain in Previous 2 Weeks | The Activities of Daily Living assessment comprised three questions about the effects of back pain or back problems over the previous 2-week period. The patient was asked if they had cut down on usual activities, the number of days in which the patient had cut down on usual activities and the number of days that the patient had spent at least half a day in bed because of back pain or back problems. | Baseline and 1 month | 
| Change in Activities of Daily Living - Activities Reduced Due to Back Pain in Previous 2 Weeks | The Activities of Daily Living assessment comprised three questions about the effects of back pain or back problems over the previous 2-week period. The patient was asked if they had cut down on usual activities, the number of days in which the patient had cut down on usual activities and the number of days that the patient had spent at least half a day in bed because of back pain or back problems. | Baseline, 1 month, 3 months, 6 months, and 12 months | 
| Change in Activities of Daily Living - Number of Days With Reduced Activities Due to Back Pain in Previous 2 Weeks | The Activities of Daily Living assessment comprised three questions about the effects of back pain or back problems over the previous 2-week period. The patient was asked if they had cut down on usual activities, the number of days in which the patient had cut down on usual activities and the number of days that the patient had spent at least half a day in bed because of back pain or back problems. | Baseline and 1 month | 
| Change in Activities of Daily Living - Number of Days With Reduced Activities Due to Back Pain in Previous 2 Weeks | The Activities of Daily Living assessment comprised three questions about the effects of back pain or back problems over the previous 2-week period. The patient was asked if they had cut down on usual activities, the number of days in which the patient had cut down on usual activities and the number of days that the patient had spent at least half a day in bed because of back pain or back problems. | Baseline, 1 month, 3 months, 6 months, and 12 months | 
| Change in Activities of Daily Living - Number of Days in Bed Due to Back Pain in Previous 2 Weeks | The Activities of Daily Living assessment comprised three questions about the effects of back pain or back problems over the previous 2-week period. The patient was asked if they had cut down on usual activities, the number of days in which the patient had cut down on usual activities and the number of days that the patient had spent at least half a day in bed because of back pain or back problems. | Baseline and 1 month | 
| Change in Activities of Daily Living - Number of Days in Bed Due to Back Pain in Previous 2 Weeks | The Activities of Daily Living assessment comprised three questions about the effects of back pain or back problems over the previous 2-week period. The patient was asked if they had cut down on usual activities, the number of days in which the patient had cut down on usual activities and the number of days that the patient had spent at least half a day in bed because of back pain or back problems. | Baseline, 1 month, 3 months, 6 months, and 12 months | 
| Ambulatory Status Change From Baseline to One Month | Ambulatory status was assessed using a three-category system, fully ambulatory, ambulatory with assistance, or not ambulatory. | 1 month | 
| Ambulatory Status Change | Ambulatory status was assessed using a three-category system, fully ambulatory, ambulatory with assistance, or not ambulatory. | Baseline, 7 days, 1 month, 3 months, 6 months, and 12 months | 
| Index Spinal Deformity Change Measured by Index Vertebral Body Angles From Baseline to 1 Month | Index spinal deformity was measured by Kyphotic angle, local Cobb angle, thoracic and lumbar Cobb angle, and anterior, middle and posterior vertebral body heights for each index VCF. | Baseline and 1 month | 
| Index Spinal Deformity Change Measured by Index Vertebral Body Angles | Index spinal deformity was measured by Kyphotic angle, local Cobb angle, thoracic and lumbar Cobb angle, and anterior, middle and posterior vertebral body heights for each index VCF. | Baseline, post-operation, 1 month, and 12 months | 
| Index Spinal Deformity Change Measured by Index Vertebral Body Height Ratio | Index spinal deformity was measured by Kyphotic angle, local Cobb angle, thoracic and lumbar Cobb angle, and anterior, middle and posterior vertebral body heights for each index VCF. Index Vertebral Body Height Ratio (VBHR) was defined as index vertebra height divided by the average of normal superior and inferior adjacent vertebrae. | Baseline and 1 month | 
| Index Spinal Deformity Change Measured by Index Vertebral Body Height Ratio | Index spinal deformity was measured by Kyphotic angle, local Cobb angle, thoracic and lumbar Cobb angle, and anterior, middle and posterior vertebral body heights for each index VCF. Index Vertebral Body Height Ratio (VBHR) was defined as index vertebra height divided by the average of normal superior and inferior adjacent vertebrae. | Baseline, post-operation, 1 month, and 12 months | 
| Back Pain Analgesics Used |  | Baseline, 7 days, and 1 month | 
| Back Pain Analgesics Used |  | Baseline, 7 days, 1 month, 3 months, 6 months, and 12 months | 
| Change in Neurology Status From Baseline (Motor Strength) | The neurological examination included motor strength, sensory examination, reflexes below the level of the most cephalad index vertebral body fracture, and the presence of radicular pain. Evaluation criteria of motor strength (scored 0-5) for rectus abdominis, hip extensors and flexors, knee extensors and flexors, and foot plantar and dorsiflexors as following: absent voluntary contraction = 0, contractions unable to move joint = 1, movement with gravity eliminated = 2, movement against gravity = 3, movement against resistance = 4, full strength = 5 | 1 month | 
| Change in Neurology Status From Baseline (Motor Strength)-Per Protocol | The neurological examination included motor strength, sensory examination, reflexes below the level of the most cephalad index vertebral body fracture, and the presence of radicular pain. Evaluation criteria of motor strength (scored 0-5) for rectus abdominis, hip extensors and flexors, knee extensors and flexors, and foot plantar and dorsiflexors as following: absent voluntary contraction = 0, contractions unable to move joint = 1, movement with gravity eliminated = 2, movement against gravity = 3, movement against resistance = 4, full strength = 5 | 1 month, 3 months, 6 months, and 12 months | 
| Change in Neurological Status From Baseline (Sensory Examination) | The neurological examination included motor strength, sensory examination, reflexes below the level of the most cephalad index vertebral body fracture, and the presence of radicular pain. For sensory examination, the Investigator assessed sensory status at baseline and a change from baseline beginning with the most cephalad index level treated through L5. | 1 month | 
| Change in Neurological Status From Baseline (Sensory Examination) | The neurological examination included motor strength, sensory examination, reflexes below the level of the most cephalad index vertebral body fracture, and the presence of radicular pain. For sensory examination, the Investigator assessed sensory status at baseline and a change from baseline beginning with the most cephalad index level treated through L5. | 1 months, 3 months, 6 months, and 12 months | 
| Change in Neurological Status From Baseline (Reflex Strength) | The neurological examination included motor strength, sensory examination, reflexes below the level of the most cephalad index vertebral body fracture, and the presence of radicular pain. Evaluation criteria of reflexes (scored 0-3) for patellar and Achilles reflexes as following: absent = 0, hypoactive = 1, normal = 2, brisk or clonus = 3 | 1 month | 
| Change in Neurological Status From Baseline (Reflex Strength) | The neurological examination included motor strength, sensory examination, reflexes below the level of the most cephalad index vertebral body fracture, and the presence of radicular pain. Evaluation criteria of reflexes (scored 0-3) for patellar and Achilles reflexes as following: absent = 0, hypoactive = 1, normal = 2, brisk or clonus = 3 | 1 months, 3 months, 6 months, and 12 months | 
| Change in Neurological Status From Baseline (Limb Strength) | The neurological examination included motor strength, sensory examination, reflexes below the level of the most cephalad index vertebral body fracture, and the presence of radicular pain. Radicular lower limb pain was assessed the presence of paresthesia, weakness, and/or painful straight leg raising (SLR). | 1 month | 
| Change in Neurological Status From Baseline (Limb Strength) | The neurological examination included motor strength, sensory examination, reflexes below the level of the most cephalad index vertebral body fracture, and the presence of radicular pain. Radicular lower limb pain was assessed the presence of paresthesia, weakness, and/or painful straight leg raising (SLR). | 1 months, 3 months, 6 months, and 12 months | 
| Rate of Study Treatment-related Adverse Events Within 30 Days of Baseline | The study treatment-related AEs were defined as follows: Related defined as the AE had a direct relationship to a Sponsor medical device used in the study patient. Possibly related defined as the AE may have had a relationship to a Sponsor medical device but an alternative cause may be equally or less likely associated. Unrelated defined as the AE was due to the underlying indication or disease state or to concomitant medication or therapy not related to any Sponsor device. Unknown defined as the relationship of the AE to a Sponsor device could not be determined. | 1 month | 
| Rate of Study Treatment-related Adverse Events Till Study Completion | The study treatment-related AEs were defined as follows: Related defined as the AE had a direct relationship to a Sponsor medical device used in the study patient. Possibly related defined as the AE may have had a relationship to a Sponsor medical device but an alternative cause may be equally or less likely associated. Unrelated defined as the AE was due to the underlying indication or disease state or to concomitant medication or therapy not related to any Sponsor device. Unknown defined as the relationship of the AE to a Sponsor device could not be determined. | 12 months | 
| Rate of Subsequent Vertebral Body Fractures |  | 1 month | 
| Rate of Subsequent Vertebral Body Fractures | Based on patients with at least 7 analyzable vertebrae. | 1 month and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Balloon Kyphoplasty, Cancer, Vertebral Compression Fracture, Back Pain, Spine