Clinical trial NCT04540601: Antiresorptive Drug Continuation Compared With Drug Holiday in Cancer Patients Needing Tooth Extraction
Official title: Antiresorptive Drug Continuation Compared With Drug Holiday in Cancer Patients Needing Tooth Extraction - A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteonecrosis Due to Drugs, Jaw
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Department of Oral and Maxillofacial Surgery, Copenhagen University Hospital
First posted: 2020-09-07
Enrollment: 30
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Development of osteonecrosis of the jaw (ONJ) or incomplete healing at 3 months follow-up
timeFrame: 3 months follow-up
measure: EQ-5D-5L: Change in patients health related quality of life from allocation/enrollment
timeFrame: 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:
measure: Pain from the jaw
timeFrame: 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.
measure: Incidence of unwanted skeletal events
timeFrame: Incidence (number of) unwanted skeletal events during the period and is registered at 3 and 6 months follow-up.
measure: Progression of cancer disease
timeFrame: The patient will be weighted at baseline, time of tooth removal, 1 month follow-up, 3 and 6 months follow-up visit.
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital
state: Copenhagen Ø
city: Copenhagen
country: Denmark
facility: University of Copenhagen, Department of Odontology
state: Nørrebro
Study officials:
References: