ZOSTER: Multicentre Medical-economic Study Evaluating the Efficacy of Adding ZOlédronique Acid to STERéotaxique Radiotherapy in the Treatment of Vertebral Metastases

Sponsor

Institut Cancerologie de l'Ouest (Other)

Overall Status

Recruiting

CT.gov ID

NCT03951493

Collaborator

(none)

225

Enrollment

Locations

Arms

40.3

Anticipated Duration (Months)

32.1

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Hypo-fractured radiotherapy in stereotactic conditions (RSHF) of bone metastases allows high doses to be delivered to the affected bone segment while sparing adjacent healthy tissues as well as possible. In addition, it not only reduces pain and prevents spinal cord compression, but also improves long-term control of metastatic disease.

Zoledronic acid reduces bone complications. The economic literature shows that stereotactic radiotherapy, like zoledronic acid, are cost-effective strategies in these indications. The objective of this research project is to evaluate the efficiency of adding zoledronic acid to stereotactic radiotherapy in the treatment of vertebral metastases.

Condition or Disease	Intervention/Treatment	Phase
Vertebral Metastasis	Combination Product: Zoledronic Acid 4Mg Solution for Injection + Hypo-fractured radiotherapy in stereotactic conditions Radiation: Hypo-fractured radiotherapy in stereotactic conditions	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

225 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase III Randomized, Controlled, Open, Multicentre Medical-economic Study Evaluating the Efficacy of Adding ZOlédronique Acid to STERéotaxique Radiotherapy in the Treatment of Vertebral Metastases

Actual Study Start Date :

Jun 23, 2020

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RSHF + zoledronic acid Patients receive RSHF according to : 30 Gy in 5 fractions of 6 Gy spaced 48 hours or 27 Gy in 3 fractions of 9 Gy spaced 48 hours or 20 Gy in 1 fraction. combined with zoledronic acid (4 mg IV slow monthly for 12 months, dose adjusted according to creatinine clearance).	Combination Product: Zoledronic Acid 4Mg Solution for Injection + Hypo-fractured radiotherapy in stereotactic conditions All patients receive radiotherapy i.e. treatment on D1, D3 and D5. Several radiotherapy schemes are possible: 20 Gy in 1 fraction; 27 Gy in 3 fractions of 9 Gy 30 Gy in 5 fractions of 6 Gy. All patients in the experimental arm receive an intravenous injection of at least 15 minutes of 4 mg zoledronic acid every month for 12 months. The first injection must be made no more than 3 weeks before the first day of radiotherapy. It can be performed up to J1 of radiotherapy. The injections will be carried out either at the patient's home by the nurses or in the investigator centre.
Active Comparator: RSHF Patients receive only RSHF according to : 30 Gy in 5 fractions of 6 Gy spaced 48 hours or 27 Gy in 3 fractions of 9 Gy spaced 48 hours or 20 Gy in 1 fraction.	Radiation: Hypo-fractured radiotherapy in stereotactic conditions All patients receive radiotherapy i.e. treatment on D1, D3 and D5. Several radiotherapy schemes are possible: 20 Gy in 1 fraction; 27 Gy in 3 fractions of 9 Gy 30 Gy in 5 fractions of 6 Gy.

Arm

Intervention/Treatment

Experimental: RSHF + zoledronic acid

Patients receive RSHF according to : 30 Gy in 5 fractions of 6 Gy spaced 48 hours or 27 Gy in 3 fractions of 9 Gy spaced 48 hours or 20 Gy in 1 fraction. combined with zoledronic acid (4 mg IV slow monthly for 12 months, dose adjusted according to creatinine clearance).

Combination Product: Zoledronic Acid 4Mg Solution for Injection + Hypo-fractured radiotherapy in stereotactic conditions

All patients receive radiotherapy i.e. treatment on D1, D3 and D5. Several radiotherapy schemes are possible: 20 Gy in 1 fraction; 27 Gy in 3 fractions of 9 Gy 30 Gy in 5 fractions of 6 Gy. All patients in the experimental arm receive an intravenous injection of at least 15 minutes of 4 mg zoledronic acid every month for 12 months. The first injection must be made no more than 3 weeks before the first day of radiotherapy. It can be performed up to J1 of radiotherapy. The injections will be carried out either at the patient's home by the nurses or in the investigator centre.

Active Comparator: RSHF

Patients receive only RSHF according to : 30 Gy in 5 fractions of 6 Gy spaced 48 hours or 27 Gy in 3 fractions of 9 Gy spaced 48 hours or 20 Gy in 1 fraction.

Radiation: Hypo-fractured radiotherapy in stereotactic conditions

All patients receive radiotherapy i.e. treatment on D1, D3 and D5. Several radiotherapy schemes are possible: 20 Gy in 1 fraction; 27 Gy in 3 fractions of 9 Gy 30 Gy in 5 fractions of 6 Gy.

Outcome Measures

Primary Outcome Measures

Differential Cost Result Ratio (DCRR) expressed as cost per year of life earned in good health [24 months]
The determination of the DCRR includes Identification of care consumption ; The measurement of costs ; overall survival at 2 years ; Calculation of utilities using the EQ5D-5L questionnaire

Secondary Outcome Measures

Survival without vertebral compression fractures [At 12 months and 24 months]
Pain control [at inclusion, 12 and 24 months]
Pain control will be assessed using a visual analogue scale (VAS) that measures pain intensity, prevents it, initiates or monitors drug or non-drug treatment, and the Brief Pain inventory, a questionnaire that quickly assesses the severity of pain and its impact on the patient's daily life.
Survival without bone complication [At 12 months and 24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Cancer with inoperable thoracic and/or lumbar vertebral metastasis;
Age ≥ 18 years old ;
Life expectancy greater than 1 year;
OMS or PS ≤ 2 ;
Effective contraception for women of childbearing age;
Patient information and free, informed and written consent, signed by the patient and investigator;
Patient affiliated or beneficiary of the social security system.

Exclusion Criteria:

Cancer with inoperable thoracic and/or lumbar vertebral metastasis;
Painful patient unable to maintain a lying position for 30 minutes despite analgesic treatment;
Patient who has received external irradiation from the proposed irradiation area > 20 Gy ;
Signs of neurological compression;
Spinal cord compression or epidural damage requiring surgery before radiotherapy;
Clinically significant hypersensitivity to zoledronic acid, other bisphosphonates or any excipient;
History of osteonecrosis of the maxilla or bone exposure or delayed healing after dental surgery;
Previous (less than 2 years) or ongoing treatment with a bisphosphonate;
Creatinine clearance < 30 ml/min;
Pregnant or breastfeeding woman;
Patient protected or under guardianship or incapable of giving consent;
Impossibility to submit to the medical follow-up of the trial for geographical, social or psychological reasons.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Institut BERGONIE	Bordeaux	France	33000
2	Institut de Cancérologie de Lorraine	Nancy	France
3	Hôpital Privé du Confluent	Nantes	France	44277
4	Centre de Haute Energie	Nice	France	06000
5	Hopital Lyon Sud	Pierre-Bénite	France	69310
6	Centre Henri Becquerel	Rouen	France	76038
7	Stéphane SUPIOT	Saint-Herblain	France	44805