Multicentre, randomized, controlled, open-label, multi-centre medicoeconomic study evaluating the efficacy of adding zoledronic acid or denosumab to Stereotaxic radiotherapy in the treatment of vertebral metastases (ZOSTER)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut De Cancerologie De L Ouest

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Jul 2020 → ongoing

Decision date (initial)

2024-06-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

INCA (AAP DOM) · DGOS Inca PRME 2017 (PRME17-0118)

External identifiers

EU CT number

2024-513248-27-00

EudraCT number

2019-001209-26

ClinicalTrials.gov

NCT03951493

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacoeconomic, Therapy, Efficacy

to evaluate, on the basis of a cost-utility analysis and a randomised phase 3 study, the efficacy of adding zoledronic acid or denosumab to stereotactic radiotherapy in the treatment of vertebral metastases

Secondary objectives 11

1. Cost-effectiveness analysis
2. Budget impact analysis
3. Determination of vertebral compression fracture-free survival (vertebral compression)
4. Bone complication-free survival (fracture, cementoplasty, bone surgery and spinal cord compression)
5. Assessment of toxicity;
6. Assessment of pain control
7. Assessment of local control of irradiated tumour lesions
8. Assessment of neoplastic spinal instability
9. Assessment of bone density
10. Biological collection to determine a profile of immunological response and markers of bone remodelling after hypofractionated radiotherapy under stereotactic conditions and determination of the impact of zoledronic acid or denosumab on these biomarkers.
11. Determination by deep learning of a predictive model for the occurrence of a bone fracture at 1 year based on imaging examinations.

Conditions and MedDRA coding

Patients, men or women over 18 old, with inoperable vertebral bone metastases who must beneficit treatment with stereotactic radiotherapy

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Cancer with inoperable thoracic and/or lumbar vertebral metastases
2. Age ≥ 18 years
3. Life expectancy greater than 1 year
4. WHO or PS ≤ 2
5. Effective contraception for women of childbearing age
6. Informing the patient and obtaining free, informed and written consent, signed by the patient and the investigator
7. Patient affiliated to or benefiting from the social security system

Exclusion criteria 13

1. Painful patient unable to maintain a supine position for 30 minutes despite analgesic treatment;
2. suppressed
3. Signs of neurological compression
4. Spinal cord compression or epidural involvement requiring surgery prior to radiotherapy;
5. Clinically significant hypersensitivity to zoledronic acid or denosumab, other bisphosphonates or any excipient;
6. A history of osteonecrosis of the jawbone or exposed bone or delayed healing after dental surgery;
7. Previous bisphosphonate treatment within the last 24 months or ongoing at inclusion;
8. Creatinine clearance < 30 ml/min;
9. Pregnant or breast-feeding woman;
10. Patient under guardianship or unable to give consent;
11. Inability to undergo medical monitoring of the trial for geographical, social or psychological reasons.
12. Previous treatment with desonumab within the last 6 months or ongoing at inclusion.
13. Patients with severe untreated hypocalcaemia.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. of life gained in good health. Calculating the ICER requires : - Identifying care consumption; - Measuring costs; - Estimating overall survival; - Calculating utilities using the EQ5D-5L questionnaire (appendix 11). The ROCR will be measured at 6 months and 24 months after the start of radiotherapy.

Secondary endpoints 11

1. Cost-effectiveness analysis: calculation of a Differential Cost Outcome Ratio (DCOER) expressed as a cost per life-year gained measured at 6 months and 24 months from the start of radiotherapy;
2. Budget impact analysis: estimation of the target and reached populations, calculation of the additional costs and avoided costs generated by the diffusion of the innovation in the French healthcare system.
3. Survival without CVF (vertebral compression fractures) estimated at 6, 12 and 24 months.
4. Survival without bone complications estimated at 6, 12 and 24 months
5. Acute and delayed toxicity: according to CTCAE 5 ;
6. Pain control: VAS and BPI (appendix 12) assessed at inclusion, 6, 12 and 24 months;
7. Local control of irradiated tumour lesions: MRI and TAP and/or PET scan (quarterly monitoring or in the event of neurological signs) assessed at 6 and 12 months;
8. Neoplastic Spinal Instability Score (NSSI) assessed at inclusion, 6 and 12 months
9. Assessment of bone density: bone densitometry at inclusion, 6 and 12 months;
10. Measurement of markers of immune response and bone remodelling;
11. Sensitivity and specificity of the algorithm for detecting the risk of fracture at 1 year.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut De Cancerologie De L Ouest

Sponsor organisation

Institut De Cancerologie De L Ouest

Address

Bd Du Professeur Jacques Monod

City

St Herblain

Postcode

44800

Country

France

Scientific contact point

Organisation

Institut De Cancerologie De L Ouest

Contact name

Stéphane SUPIOT

Public contact point

Organisation

Institut De Cancerologie De L Ouest

Contact name

Emilie DEBEAUPUIS

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications