Antiresorptive Drug Continuation Compared With Drug Holiday in Cancer Patients Needing Tooth Extraction (DrugHoliday)

September 7, 2020 updated by: Camilla Ottesen, University of Copenhagen

Antiresorptive Drug Continuation Compared With Drug Holiday in Cancer Patients Needing Tooth Extraction - A Randomized Clinical Trial

The aim of this trial is to evaluate high-dose antiresorptive drug holiday related to tooth extraction with primary mucosal closure (surgical extraction) including how a drug holiday affects the health related quality of life.

Research question: Does a drug holiday have any influence on health related quality of life or the incidence of developing osteonecrosis of the jaw after surgical tooth extraction? The investigators hypothesize that a drug holiday 1 month before to 3 months after surgical tooth extraction in cancer patients do not influence the development of osteonecrosis of the jaw and may even affect the health related quality of life negatively.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Osteonecrosis of the jaw is a known adverse reaction to antiresorptive medication, including bisphosphonate and denosumab. The globally accepted term is Medication-Related Osteonecrosis of the Jaws (MRONJ). Since 2003 there has been a worldwide focus at medication-related osteonecrosis, even though there still exist several of unanswered questions - one of them is the effect of a drug holiday in relation to tooth extraction. A drug holiday is a temporary discontinuation of a drug and has been suggested among risk reduction strategies in the literature. It is still unknown whether a drug holiday plays a significant role in relation to tooth extraction for the development of osteonecrosis. The investigators want to investigate the importance of an antiresorptive drug holiday (bisphosphonate, denosumab) in relation to tooth extraction.

The aim of this trial is therefore to clarify the meaning of high-dose antiresorptive drug holiday related to tooth extraction with primary mucosal closure in cancer patients and reveal how a drug holiday affects the health related quality of life. A continuation of the patients' antiresorptive treatment can possibly lead to increased risk of osteonecrosis of the jaw, but with the operation procedure with primary closure it is unlikely. It is beneficial for the cancer patients to continue the high dose antiresorptive therapy because a drug holiday is a stop in their anti-cancer treatment with risk of increased pain as well as unwanted skeletal events to occur, and potentially progress of metastases to follow.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Copenhagen Ø
      • Copenhagen, Copenhagen Ø, Denmark, 2100
        • Copenhagen University Hospital
    • Nørrebro
      • Copenhagen, Nørrebro, Denmark, 2200
        • University of Copenhagen, Department of Odontology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients eligible for the trial must comply with all of the following at randomization:
  • Patients aged 18 years or older.
  • Patients with malignant disease (breast or prostate cancer, multiple myeloma) and metastases to the skeleton.
  • Patients present high dose/intravenous antiresorptive therapy for at least 1 month.
  • Patients who need tooth extraction. Indications for extraction include root fracture, endodontic failure, severe periodontal disease, non-restorable caries and teeth with a poor prognosis or at high risk of infection, complications.

  • Patients who have an ECOG (Eastern Cooperative Oncology Group) score < 2 (30). Definition of ECOG 0. Fully active, able to carry on all pre-disease performance without restriction.

    1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature e.g., light house work, office work.
    2. Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of walking hours.
    3. Capable of only limited selfcare, confined to bed or chair more than 50% of walking hours.
    4. Completely disabled. Cannot carry on selfcare. Totally confined to bed or chair.
  • Signed informed content.

Exclusion Criteria:

  • Patients must not have received radiation therapy to the jaws.
  • Patients must not have exposed bone, or signs of non-exposed bone.
  • Patients previous diagnosed with ONJ.
  • Patients who are unable to cooperate or too ill to complete the experiment.
  • Lack of signed informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Cancer patients, randomized A
Patients in high-dose antiresorptives with bone metastases
Other: Continuation of antiresorptives in relation to tooth extraction (surgical tooth removal)

We want to investigate the importance of an antiresorptive drug holiday (bisphosphonate, denosumab) in relation to tooth extraction. The experimental intervention in this trial is drug continuation starting before tooth extraction with primary closure.

We simply ask the participating cancer patients to continue their high dose antiresorptive treatment for 4 months (intervention-period: 1 month pre-operative, 3 months post-operative) instead of taking a drug holiday.
No Intervention: Cancer patients, randomized B
Drug Holiday as standard operation procedure

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Development of osteonecrosis of the jaw (ONJ) or incomplete healing at 3 months follow-up
Time Frame: 3 months follow-up

The outcome assessor has 3 options for registration related to ONJ occurrence:

  • Complete healing = mucosal covering = no sign of ONJ, defined as complete wound healing; Intact mucosa, that is total mucosal covering over the tooth extraction area.
  • Incomplete healing = presence of fibrin covering partly or over all mucosal operation area; Defined as the presence of fibrin at the surface of the operation area, thus still being a wound.

  • ONJ present, defined according to the AAOMS position paper 2014 (4), all three items have to be present:

    1. Current or previous treatment with antiresorptive agents.
    2. Exposed bone or bone that can be probed through an extraoral or intraoral fistula that has persisted for longer than 8 weeks.
    3. No history of radiation therapy to the jaws or obvious metastatic disease to the jaws.
3 months follow-up
EQ-5D-5L: Change in patients health related quality of life from allocation/enrollment
Time Frame: The patient will be asked to fulfill the EQ-5D-5L at allocation/enrollment and again at 1, 3 and 6 months follow-up.
The patients are given the EQ-5D-5L questionnaire. The 5-level EQ-5D version (EQ-%D-5L) was introduced by the EuroQol Group in 2009 and consists of two pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, serve problems and extreme problems. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The Danish dataset (SPSS syntax crosswalk values EQ-5D-5L Denmark) will be used to analyze patients´ responses.
The patient will be asked to fulfill the EQ-5D-5L at allocation/enrollment and again at 1, 3 and 6 months follow-up.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pain from the jaw
Time Frame: This is asked prior to tooth extraction (time 0), at suture removal (time 10-14 days), at 1-month follow-up and at 3 and 6 months follow-up and is registered in the datasheet.
Pain from the jaw is registered by a Visual Analogue Scale (VAS). The investigator will give the patient a paper with a VAS, see attached appendix 3, and ask following question: "On a scale from 0 to 10, where 0 is no pain and 10 is the worst thinkable pain, mark at the scale how much pain you feel from your jaw at tooth operation site".
This is asked prior to tooth extraction (time 0), at suture removal (time 10-14 days), at 1-month follow-up and at 3 and 6 months follow-up and is registered in the datasheet.
Incidence of unwanted skeletal events
Time Frame: Incidence (number of) unwanted skeletal events during the period and is registered at 3 and 6 months follow-up.
The patient is giving a simple questionnaire, where they have to answer yes or no to following question: "Have you visited your own doctor or been hospitalized because of fractures or other skeletal complications during this trial period - yes or no. If yes, please write why." See attached appendix 4: Skeletal-related event questionnaire
Incidence (number of) unwanted skeletal events during the period and is registered at 3 and 6 months follow-up.
Progression of cancer disease
Time Frame: The patient will be weighted at baseline, time of tooth removal, 1 month follow-up, 3 and 6 months follow-up visit.
The tumor-evaluation will be done by the oncologic doctor in due to their departments routine.
The patient will be weighted at baseline, time of tooth removal, 1 month follow-up, 3 and 6 months follow-up visit.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Copenhagen

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Department of Oral and Maxillofacial Surgery, Copenhagen University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 10, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 19, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 24, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 31, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 7, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 10, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 7, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • H-18007990

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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