CAFE Study - Cancer Patient Fracture Evaluation

• Study Treatment-related Adverse Events and Change in Neurological Status [ Time Frame: Baseline, 1 Month , 3 Month, 6 Month and 12 Month ] [ Designated as safety issue: Yes ]
• Clinical: Change in Functional Status (as Assessed With the Roland-Morris Disability Questionnaire and the Karnofsky Performance Scale) [ Time Frame: Baseline, 1 Month , 3 Month, 6 Month and 12 Month ] [ Designated as safety issue: No ]
• Change in Quality of Life (as Assessed by the SF-36v2™ Health Survey) [ Time Frame: Baseline, 1 Month, 3 Month, 6 Month and 12 Month ] [ Designated as safety issue: No ]
• Change in Back Pain (as Measured by a 10-point Numerical Rating Scale) [ Time Frame: Baseline, 7-10 Day Phone Call, 1 Month, 3 Month, 6 Month and 12 Month ] [ Designated as safety issue: Yes ]
• Radiographic: Change in Spinal Deformity, Defined as the Degree of Spine Angulation (as Assessed by an Independent Radiologist at the Core Laboratory) [ Time Frame: Baseline, Pre-op, Post-Op, 1 Month and 12 Month ] [ Designated as safety issue: Yes ]
• Radiographic: Rate of Subsequent Vertebral Body Fractures (as Assessed by Independent Radiologists at the Core Laboratory) [ Time Frame: Baseline, Pre-op, Post-Op, 1 Month and 12 Month ] [ Designated as safety issue: Yes ]

• 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
• o the Roland-Morris Disability Questionnaire
• o the 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

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.

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

  • the Roland-Morris Disability Questionnaire
  • the 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.

• Cancer
• Spinal Fractures

• Device: Balloon Kyphoplasty
  Vertebral Augmentation
  Other Name: KyphX Inflatable Bone Tamps
• Other: Non Surgical Management
  Non-surgical treatment aimed at alleviation of back pain and restoration of decreased function associated with VCF(s).

• Experimental: Balloon Kyphoplasty (BKP)
  Randomized, Unblinded Controlled Study
  Intervention: Device: Balloon Kyphoplasty
• Active Comparator: Non Surgical Management
  Non-surgical treatment aimed at alleviation of back pain and restoration of decreased function associated with VCF(s).
  Intervention: Other: Non Surgical Management

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