Trial of Combined Radiotherapy and Vertebroplasty for Patients With Painful Metastatic Spinal Lesions

A Phase II Randomized Trial of Combined Radiotherapy and Vertebroplasty to Improve the Quality of Life of Patients With Painful Metastatic Localized Spinal Lesions

Since patients with spinal metastases are living longer, durable palliation with long-term tumor control are becoming increasingly important.

EBRT results in durable local control of bone metastasis. However, about 25 % of patients with spinal metastases only achieved complete pain relief following EBRT for a median duration of less than 4 months. This could be partly due to spinal instability. In addition, almost half of the patients who receive EBRT will subsequently develop VCFs . Hence, RT does not stabilize the spine secondary to VCFs and is not effective in preventing imminent VCFs. Vertebroplasty has rapidly reduced pain and improved function in patients with VCFs. However, vertebroplasty does not provide local tumor control similar to EBRT.

It is theorized that combining vertebroplasty with EBRT will stabilize the spine, relieve the pain, prevent imminent VCFs and minimize or avoid the need for opioids. It is hypothesized that combining a spine stabilization procedure such as vertebroplasty with RT will be the most effective management for patients with spinal metastases than RT alone for patients with spinal metastases. Combined vertebroplasty and radiotherapy is not a standard treatment option at present. This study is designed to quantify the advantage of adding vertebroplasty to radiotherapy for patients with spinal metastases. If the study is proven to be significant, it could become the standard of care for patients with spinal metastases.

Study Overview

• Status: Not yet recruiting
• Conditions: Spinal Metastases
• Intervention / Treatment: Radiation: Radiotherapy; Procedure: Vertebropladty

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants capable of giving informed consent, or if appropriate, participants having an acceptable individual capable of giving consent on the participant's behalf
2. Patients must be 18 years of age or older
3. Spinal vertebral metastases confirmed by CT, MRI or bone scan.
4. Patients with painful (VAS of at least ≥ 2) vertebral spinal metastases in the thoracic and /or lumbar spine (not cervical).
5. Patients must be willing and able to comply with schedule visits, treatment plan, tests and other study procedures
6. Life expectancy > 6 months. Life expectancy will be evaluated by the study investigator both clinically and by using Linden model. Patient should be in the group B or C of the Linden model.
7. Patients with an ECOG score 0-2 or Karnofsky performance status of ≥ 60% will be eligible for enrolment (see appendix 1).
8. No prior EBRT to the target +/-1 vertebral body level
9. Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level > 40 mIU/mL to confirm menopause
10. Patients of childbearing / reproductive potential should use highly effective birth control methods, as defined by the investigator, during the study treatment period. A highly effective method of birth control is defined as those that result in low failure rate (i.e. less than 1% per year) when used consistently and correctly (Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard) .
11. Females must not breastfeed during study treatment.
12. Male patients should agree to not donate sperm during study treatment.
13. Absence of any condition hampering compliance with study protocols and follow-up schedule; those conditions should be reviewed with the patient prior to trial registration

Exclusion Criteria

1. Patient cannot provide consent
2. Prior radiotherapy to the target +/-1 vertebral body level
3. Life expectancy < 6 months (assessed both clinically and using Linden model)
4. Karnofsky performance status of < 60%
5. Primary bone tumors
6. Plasmacytoma
7. Communicated fracture
8. Associated Impending cord compression or spinal cord compression
9. Epidural involvement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Radiotherapy; Radiotherapy dose: 20 Gy/5 fractions/1 week or 8 Gy/1 fraction (at the discretion of the Radiation Oncologist)	Radiation: Radiotherapy; External beam radiation therapy is a type of radiation therapy used for cancer treatment. A machine is used to aim high-energy rays from outside the body into tumor; Other Names: External Beam Radiation Therapy
EXPERIMENTAL: Vertebroplasty + Radiotherapy; Vertebroplasty followed by radiotherapy within 2-3 weeks Radiotherapy dose: 20 Gy/5 fractions/1 week or 8 Gy/1 fraction (at the discretion of the Radiation Oncologist)	Radiation: Radiotherapy; External beam radiation therapy is a type of radiation therapy used for cancer treatment. A machine is used to aim high-energy rays from outside the body into tumor; Other Names: External Beam Radiation Therapy; Procedure: Vertebropladty; Vertebroplasty is a procedure for stabilizing compression fractures in the spine. Bone cement is injected into vertebrae that have cracked or broken. The cement hardens, stabilizing the fractures and supporting your spine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in Pain Score based on the Visual Analog Scale	The primary end point is the improvement in pain score of at least 2 points (a decrease of 2 points) on the visual analogue Scale (VAS) without concurrent increase in opioids.	1,3,6 and 12 months post treatment
Improvement in Pain Score based on the Brief Pain Inventory	The primary end point is the improvement in pain score of at least 2 points (a decrease of 2 points) on the Brief Pain Inventory (BPI) without concurrent increase in opioids.	1,3,6 and 12 months post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in back-specific physical functioning	The improvement in back-specific physical functioning is evaluated by the change in Roland-Morris disability questionnaire (RDQ) score.	1,3,6 and 12 months post treatment
Incidence of vertebral compression fractures post treatment.	The incidence of vertebral compression fractures will be evaluated by standing lateral spine radiographs of the thoracic and lumbar vertebrae.	Baseline, 6 months and 12 months
Prospectively quantify pain response using the Visual Analog Scale	Pain response will be assessed by VAS and evaluated using a patient diary based on the International Bone Metastases Working Party Criteria. Based on intake of analgesics, the daily oral morphine equivalent dose (OMED) will be calculated.	1,3,6 and 12 months post treatment
Prospectively quantify pain response using the Brief Pain Inventory.	Pain response will be assessed by BPI and evaluated using a patient diary based on the International Bone Metastases Working Party Criteria. Based on intake of analgesics, the daily oral morphine equivalent dose (OMED) will be calculated.	1,3,6 and 12 months post treatment

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta
• Collaborators: Cross Cancer Institute

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2020
• Primary Completion (ANTICIPATED): September 1, 2022
• Study Completion (ANTICIPATED): March 1, 2024

Study Registration Dates

• First Submitted: January 21, 2020
• First Submitted That Met QC Criteria: January 23, 2020
• First Posted (ACTUAL): January 27, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 13, 2020
• Last Update Submitted That Met QC Criteria: April 9, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Radiotherapy; Vertebroplasty; Vertebral Compression Fracture
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: IIT-0008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No