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

• ClinicalTrials.gov Identifier: NCT03951493
• Recruitment Status: Recruiting
• First Posted: May 15, 2019
• Last Update Posted: April 28, 2022
• Sponsor: Institut Cancerologie de l'Ouest
• Information provided by (Responsible Party): Institut Cancerologie de l'Ouest

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 (Clinical Trial)
• Estimated 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: June 23, 2020
• Estimated Primary Completion Date: November 1, 2023
• Estimated Study Completion Date: November 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.

Outcome Measures

Primary Outcome Measures :

1. Differential Cost Result Ratio (DCRR) expressed as cost per year of life earned in good health [ Time Frame: 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 :

1. Survival without vertebral compression fractures [ Time Frame: At 12 months and 24 months ]
2. Pain control [ Time Frame: 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.
3. Survival without bone complication [ Time Frame: At 12 months and 24 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts

Contact: Stéphane SUPIOT, MD; +33240679900; stephane.supiot@ico.unicancer.fr

Locations

France

Institut BERGONIE; Recruiting

Bordeaux, France, 33000

Contact: Stéphanie BATARD, MD s.batard@bordeaux.unicancer.fr

Principal Investigator: Stéphanie BATARD, MD

Institut de Cancérologie de Lorraine; Recruiting

Nancy, France

Contact: JEAN-CHRISTOPHE FAIVRE, MD jc.faivre@nancy.unicancer.fr

Principal Investigator: Jean-Christophe FAIVRE, MD

Hôpital Privé du Confluent; Not yet recruiting

Nantes, France, 44277

Contact: Xavier BUTHAUD, MD xavier.buthaud@groupeconfluent.fr

Principal Investigator: Xavier BUTHAUD, MD

Centre de Haute Energie; Not yet recruiting

Nice, France, 06000

Contact: René-Jean BENSADOUN, MD renejean.bensadoun@che-nice.com

Principal Investigator: René-Jean BENSADOUN, MD

Hopital Lyon Sud; Recruiting

Pierre-Bénite, France, 69310

Contact: Ariane LAPIERRE, MD ariane.lapierre@chu-lyon.fr

Principal Investigator: Ariane LAPIERRE, MD

Centre Henri Becquerel; Recruiting

Rouen, France, 76038

Contact: SEBASTIEN THUREAU, MD sebastien.thureau@chb.unicancer.fr

Principal Investigator: Sébastien THUREAU, MD

Stéphane SUPIOT; Recruiting

Saint-Herblain, France, 44805

Contact: Stéphane SUPIOT, MD +33240679900 stephane.supiot@ico.unicancer.fr

Principal Investigator: Stéphane SUPIOT, MD

Sponsors and Collaborators

Institut Cancerologie de l'Ouest

Investigators

• Study Director: Stéphane SUPIOT, MD; ICO site SAINT HERBLAIN

More Information

• Responsible Party: Institut Cancerologie de l'Ouest
• ClinicalTrials.gov Identifier: NCT03951493
• Other Study ID Numbers: ICO-N-2018-14
• First Posted: May 15, 2019
• Last Update Posted: April 28, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Institut Cancerologie de l'Ouest:

Hypo-fractured radiotherapy in stereotactic conditions (RSHF); zoledronic acid; medico-economic; vertebral compressive fracture

Additional relevant MeSH terms:

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Zoledronic Acid; Bone Density Conservation Agents; Physiological Effects of Drugs