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

NCT04540601 | Completed DMC

• 1 other identifier: H-18007990
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Osteonecrosis Due to Drugs, Jaw

Outcome Measures

Primary Outcomes (2)

• Development of osteonecrosis of the jaw (ONJ) or incomplete healing at 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

  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 Outcomes (3)

• Pain from the jaw

  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

  Incidence (number of) unwanted skeletal events during the period and is registered at 3 and 6 months follow-up.

• Progression of cancer disease

  The patient will be weighted at baseline, time of tooth removal, 1 month follow-up, 3 and 6 months follow-up visit.

Study Arms (2)

Cancer patients, randomized A

ACTIVE COMPARATOR

Patients in high-dose antiresorptives with bone metastases

Other: Continuation of antiresorptives in relation to tooth extraction (surgical tooth removal)

Cancer patients, randomized B

NO INTERVENTION

Drug Holiday as standard operation procedure

Interventions

Continuation of antiresorptives in relation to tooth extraction (surgical tooth removal) OTHER

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.

Cancer patients, randomized A

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of walking hours.
• Capable of only limited selfcare, confined to bed or chair more than 50% of walking hours.
• Completely disabled. Cannot carry on selfcare. Totally confined to bed or chair.
• Signed informed content.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Copenhagen: lead
• Department of Oral and Maxillofacial Surgery, Copenhagen University Hospital: collaborator

Study Sites (2)

Copenhagen University Hospital

Copenhagen, Copenhagen Ø, 2100, Denmark

Location

University of Copenhagen, Department of Odontology

Copenhagen, Nørrebro, 2200, Denmark

Location

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The allocation of the patients is not known to the clinical investigator, the surgeon or the outcome assessor but to the patient's oncologic doctor and nurse, who are in charge of drug delivery, and a supervisor (Klaus Gotfredsen) not involved in any registrations or surgeries. The participating patients will not be blinded. The patients do know which group they are randomized to and therefore do know if they are treated with or without drug holiday during the trial period (1+3 months). The patients are carefully instructed not to reveal which group they belong during the trial to the assessor. Klaus Gotfredsen will make sure that the patients randomized to the intervention group will continue their antiresorptive therapy and the patients randomized to the control group will be treated with drug holiday this in close collaboration with the oncological departments. The medicine will be giving to the patient by the department's nurse.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: DDS, PhD fellow

Model Details: This trial is designed as an investigator-initiated, parallel-group, randomized, clinical, single-blinded, trial investigating no antiresorptive drug holiday starting before tooth extraction with primary closure versus antiresorptive drug holiday starting before tooth extraction with primary closure in cancer patients

Study Record Dates

• First Submitted: August 24, 2020
• First Posted: September 7, 2020
• Study Start: July 10, 2018
• Primary Completion: August 1, 2019
• Study Completion: August 19, 2020
• Last Updated: September 10, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)