AzTrials
AzTrials

Osteoid OsteomaPhase 3BISPHOONCT02739555

Zoledronic Acid Compared to Percutaneous Treatment in Osteoid Osteoma

A Phase 3 study testing Thermal destruction with radiofrequency or laser and Acide Zoledronique in people with Osteoid Osteoma, run by Assistance Publique - Hôpitaux de Paris at 16 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

Osteoid osteoma (OO) is a benign osteogenic tumor occurring in children and young adults, responsible for intense bone pain, which has a tendency to spontaneously heal with mineralization of the nidus, but extremely slowly. This healing may be accelerated in patients taking NSAIDs regularly during a few years. Read more about this study

Who is it for?
Ages 10 years and older
Conditions the study is for
Osteoid Osteoma
What is being tested?
Thermal destruction with radiofrequency or laser and Acide Zoledronique
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
16 sitesFrance
Study dates
23 Jun 2016to 28 Jun 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age superior or equal to 10 years
  • Patient with a typical osteoid osteoma diagnosed on clinical and radiological criteria (MRI and scanner), validated by a binomial clinician / radiologist.
  • OO never treated or in treatment failure, or recurrent OO.
  • OO percutaneously accessible
  • Pain intensity is superior or equal to 40 mm on a VAS at inclusion visit.
  • Written informed consent signed by the patient or his representative (for minors, agreement of the child and signature of the two mandatory parents).
  • Patient affiliated to the social security.

Who cannot join

  • Patients with other diseases or receiving treatment that may impact on bone tissue or its metabolism.
  • Patients suffering from renal failure (i.e. lower than 60 ml/min according to the Cowcroft equation).
  • Patients with severe hepatocellular insufficiency (TP<50%).
  • Patients with a history of iritis or uveitis.
  • Patient with untreated rickets or osteomalacia.
  • Patient with untreated dental infection or planed dental surgery during the study period.
Show all 17Show fewer
  • Patient with untreated infection of the external auditory canal (ex: furuncle, eczema superinfection)
  • Patient already treated by bisphosphonates.
  • Patients with hypersensitivity to the active substance, to other bisphosphonates or to any of the excipients (List of excipients: mannitol (E421), sodium citrate (E331), water for injections).
  • Patient enrolled in another biomedical research protocol and during the whole study
  • Pregnant or breastfeeding women, or planning pregnancy during the course of the study
  • Women of child bearing potential (women following menarche and until post-menopause) and sexually active, without an effective contraceptive measure during the period of treatment (hormonal contraception or mechanical contraception)*
  • Oral contraceptive methods include:
  • combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravagina or transdermal)
  • progestogen-only hormonal contraception associated with inhibition of ovulation (oral, intravagina or transdermal).
  • Mechanical methods of contraception include intrauterine device and intrauterine hormone-releasing system.Patient enrolled in another biomedical research protocol and during the whole study
  • Patients who would not meet the inclusion criteria "OO percutaneously accessible" will be offered to participate in a register, only in Lariboisière hospital. This register will target specifically children aged of at least 12 years old and adults.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

France16 sites
  • Hopital PELLEGRIN - Service d'imagerie diagnostique et interventionnelle de l'adulte

    Bordeaux, 33000

  • Hopital PELLEGRIN - Service rhumatologie

    Bordeaux, 33000

  • Hôpital ROGER SALENGRO - Service d'Orthopédie A

    Lille, 590000

  • Hôpital ROGER SALENGRO - Radiologie et imagerie musculo-squelettique

    Lille, 59000

  • Hôpital ROGER SALENGRO - Rhumatologie

    Lille, 59000

  • Hôpital LAPEYRONIE - Imagerie médicale

    Montpellier, 34000

  • Hôpital LAPEYRONIE - Service Rhumatologie

    Montpellier, 34000

  • CHU Nancy - Imagerie Guilloz

    Nancy, 54000

  • Hôpital LARIBOSISIERE - Service radiologie ostéo-articulaire

    Paris, 75010

  • Hôpital LARIBOSISIERE - Service rhumatologie

    Paris, 75010

  • Hôpital COCHIN - Service radiologie B

    Paris, 75014

  • Hôpital COCHIN - Service rhumatologie B

    Paris, 75014

  • Hopital SUD - Service Radiologie

    Rennes, 35200

  • Hôpital SUD - Service rhumatologie

    Rennes, 35200

  • Hôpital PURPAN - Serice Radiologie

    Toulouse, 31000

  • Hôpital PURPAN - Serice Rhumatologie

    Toulouse, 31000

Other trials in France

About this study

Official title: Non-inferiority Trial of Three Cycles of Zoledronic Acid Versus Percutaneous Thermal Ablation in Osteoid Osteoma

Osteoid osteoma (OO) is a benign osteogenic tumor occurring in children and young adults, responsible for intense bone pain, which has a tendency to spontaneously heal with mineralization of the nidus, but extremely slowly. This healing may be accelerated in patients taking NSAIDs regularly during a few years. The long delay for healing and intense pain, explain why patients are quickly directed to surgeons or specialized radiology departments for tumor ablation. But percutaneous treatment or surgical excision destruction can expose the patient to a substantial risk in terms of neurologic or joint damages, depending on the location. Bisphosphonates treatment may be an effective alternative to percutaneous treatment by accelerating the natural history of OO.

Read the detailed description

Osteoid osteomas (OOs) are small, benign but painful bone tumors, mainly observed in children and young adults. Pain, almost universal, is characteristically greater at night. Pain is well relieved by NSAIDs but resolution is not always complete and pain reappears a few hours after the last dose. Also long-term consumption of NSAID can lead to serious adverse events. Therefore OOs are usually cured shortly after diagnosis, mainly by means of percutaneous treatment (PT) under computed tomography (CT) (radiofrequency coagulation or interstitial laser ablation).

The clinical success rate using these techniques is 96% at 6-month, 94% at 24-month. However, the technique is not distributed everywhere since it is performed by highly specialized interventional radiologists. The PT is performed under general, spinal or regional anesthesia. General anesthesia is used in most cases, especially in children. When the OO is located in close proximity to the skin, cartilage, vessels and nerves, severe complications may occur and additional procedures such as infusion of saline or injection of CO2 at the interface between the OO and the vulnerable structure are done. Also few anatomic locations are not accessible to a PT.

The natural history of OOs remains poorly understood. However investigators in small series of conservatively treated OOs suggested a spontaneous healing of the lesion with mineralization of the nidus and resolution of pain (mean duration of pain in patients with NSAID treatment: 33 months NSAID).

The efficacy of bisphosphonates on pain related to benign (Langherhans cell histiocytosis, fibrous dysplasia, Paget disease) or malignant bone lesions has been widely reported. The investigators observed such efficacy in a small series of 20 patients with percutaneously hard-to-reach or recurrent OO using one to three infusions of zoledronate. The clinical efficacy assessed on pain relief was accompanied by a significantly increased mineralization of the nidus. The investigators postulated that bisphosphonates had accelerated the natural history of OO.

Our hypothesis is that three infusions of zoledronate (4mg) repeated monthly in patients with symptomatic OO is non-inferior to percutaneous treatment on the efficacy, measured by pain relief at Visual Analogical Scale (VAS).

The main objective of this randomized study is to demonstrate that in patients with OO, treatment with three intravenous cycles of 4mg of zoledronic acid administered monthly, is non-inferior to treatment with percutaneous thermal ablation on the efficacy measured by the percentage of pain relief between baseline and end of treatment.

NB: Patients for whom the OO would not be percutaneously accessible (that is to say when the percutaneous treatment or surgical excision destruction expose the patient to a substantial risk in terms of neurologic or joint damages) will be offered to participate in a cohort, only in Lariboisière and Cochin hospital in Paris. In the cohort, the clinical follow-up will be conducted as it is currently proposed in Laribosisière hospital (no act added by the research). Objectives of the register will be explained to the patient. It consists in collecting anonymized medical data after a bisphosphonate treatment to statuate on the efficacy of the bisphosphonates to relieve pain due to osteoid osteoma.

Study design of the randomized study:

  • Selection / Inclusion visit: verification of eligibility, randomization and recollection of patient consent.
  • Intervention:
  • percutaneous thermal ablation at V1 visit (i.e. maximum one month after the selection / inclusion visit)
  • or three zoledronic acid infusions at V1, V2 (one month after v1) and V3 visits (one month after V2)
  • V4 visit at 4 months (end of treatment, evaluation of the main outcome) and V7 visit at 16 months (end of study, evaluation of the secondary outcomes).
  • Option: One to 3 additional visits (V4, V5 and V6) for zoledronic acid infusion can be proposed to the patient, depending on the efficacy of the previous infusion.
Conditions
Osteoid Osteoma
Being tested
Thermal destruction with radiofrequency or laser, Acide Zoledronique
Keywords
Osteoid osteoma, Bisphophonates
Medical subject headings
Osteoma, Osteoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Thermal destruction with radiofrequency or laserDevice

  • Acide ZoledroniqueDrug

Study groups in NCT02739555
Study groupRoleWhat they receive
1: Percutaneous treatmentActive comparatorPercutaneous treatment of OO is a thermal tumor destruction by radiofrequency or laser photocoagulation performed under CT control with strict aseptic approach and most often under general anesthesia. The introductive needle is inserted toward the nidus. Then the optic fiber or the radiofrequency probe is inserted in the nidus center and thermal destruction of the tumor is obtained.When the distance between the nidus and a nerve or the skin is less than 10 mm, infusion of normal saline or CO2 is introduced as spacing agent. When the nidus is in the subchondral bone, cold normal saline is introduced in the joint to protect the cartilage. In addition, a thermocouple is placed in the epidural or foraminal space to continuously monitor the temperature. A procedure typically required between 1 and 2 h from the time the patient entered the CT unit.
Receives: Device: Thermal destruction with radiofrequency or laser
2: Bisphosphonate treatmentExperimentalThe treatment consists of 3 infusions of zoledronic acid administered at a monthly interval. Bisphosphonate treatment is considered finished 1 month after the third bisphosphonate infusion (V4 visit). In few cases, the analgesic efficacy provided by 3 bisphosphonate infusions cannot be sufficient: 1 to 3 additional infusions could be proposed to the patient. Zoledronic acid is supplied as a 4 mg/100 ml solution for infusion. It will be administered as infusion over 30 minutes under the supervision of a nurse. Adults will receive intravenous infusion of 4 mg of zoledronic acid. Children will receive infusion of 0.025 mg/kg of zoledronic acid. The investigators propose abacus corresponding to zoledronic acid volume to infuse during 30 minutes for children.
Receives: Drug: Acide Zoledronique

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of decrease in bone pain measured on a visual analog scale (VAS) between baseline and the end of treatment larger or equal to 70%.

    Percentage of decrease in bone pain measured on a visual analog scale (VAS) between baseline and the end of treatment larger or equal to 70%. End of treatment is set at one month after the third administration of bisphosphonates and three months after the percutaneous thermal destruction (ie 4 months after inclusion visit = V4 visit, for both groups).

    Measured: 4 months

Secondary outcomes (6)
  1. Pain

    arm1 : only at 16 months

    arm 2 : assessed by Visual Analog Scale as an average over the past 48 hours, at V1 (1 month +/- 5 days), V2 (2 months +/- 5 days), V3 (3 months +/- 5 days), V7 visits (16 months +/- 1 month) and, in case of additional infusions, at V5 (7 months +/- 15 days) and V6 (10 months +/- 15 days)

    Measured: at 1, 2, 3, 7, 10 and 16 months

  2. Patient'Global Impression of change (PGIC)

    arm1 : only at 16 months

    arm 2 : assessed by Visual Analog Scale as an average over the past 48 hours, at V2 (2 months +/- 5 days), V3 (3 months +/- 5 days), V7 visits (16 months +/- 1 month) and, in case of additional infusions, at V5 (7 months +/- 15 days) and V6 (10 months +/- 15 days)

    Measured: at 2, 3, 7, 10 and 16 months

  3. Consumption of analgesic and NSAIDs

    To this end, patient will be asked to note any analgesic and NSAIDs medication in a CRJ during the whole study arm1 : only at inclusion, 1, 4 and16 months

    Measured: at inclusion, 1, 2, 3, 4, 7, 10 and 16 months

  4. Nidus mineralization on CT scan images

    Measured: 4 months

  5. Surface of bone marrow edema on MR images

    Measured: at 4 and 16 months

  6. Incidence of Treatment-Emergent Adverse Events of bisphosphonates and percutaneous treatment.

    Tolerance and adverse events of bisphosphonates and percutaneous treatment. To this end, patient will be asked to note any adverse event in a CRJ during the whole study.

    arm1 : only at inclusion, 1, 4 and16 months

    Measured: at inclusion, 1, 2, 3, 4, 7, 10 and 16 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2016 (estimated)
  2. Study start23 Jun 2016
  3. Primary completion20 Apr 2018
  4. Study completion28 Jun 2019

Why it stopped: The study has been conducted until the end of the research; participants are no longer receiving an intervention or being examined; but recruitment isn't completed (15 % enrolled in the stud)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02739555
Sponsor's protocol ID
P140909
Other IDs
2015-001698-41, 2015
Acronym
BISPHOO
Status last verified
Feb 2022
First submitted
29 Mar 2016
Last updated
23 Feb 2022
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Thermal destruction with radiofrequency or laser and Acide Zoledronique in people with Osteoid Osteoma, run by Assistance Publique - Hôpitaux de Paris at 16 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study has been conducted until the end of the research; participants are no longer receiving an intervention or being examined; but recruitment isn't completed (15 % enrolled in the stud)). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of decrease in bone pain measured on a visual analog scale (VAS) between baseline and the end of treatment larger or equal to 70%. (time frame: 4 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2022.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in