Prevention of Docetaxel Induced Dacryostenosis

NCT00266838 | Completed Phase 1

• 1 other identifier: UZL OFT-ML 3386
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The antineoplastic agent Docetaxel (Taxotere®) is approved for the treatment of patients with metastatic and locally advanced breast cancer and other malignancies. There are 2 frequently used schedules of treatment with Docetaxel. Docetaxel can be administered every 3 weeks or in a weekly regimen. The efficacy seems to be similar but the toxicity profile changes. In the standard 3-weekly Docetaxel regimen the dose-limiting side effect is myelosuppression, while in the weekly regimen there is only a mild myelosuppression. On the other hand, weekly Docetaxel has a side effect that is rare in the 3-weekly schedule: epiphora (= tearing eye) caused by dacryostenosis. The underlying mechanism of dacryostenosis induced by weekly Docetaxel is fibrosis of the lacrimal puncta and canaliculi. Docetaxel has been reported to be secreted in the lacrimal tears. Direct contact between Docetaxel containing tears and the epithelial lining causes chronic inflammation of the mucosa and ultimately fibrosis of the most narrow part of the lacrimal outflow system i.e. the lacrimal puncta and canaliculi. A surgical treatment is possible for dacryostenosis. In case of subtotal stenosis of the lacrimal canaliculi, silicone intubation of the canaliculi is performed in order to prevent further closure. In the case of complete stenosis, placement of a permanent pyrex glass tube of Jones is required. To our knowledge, there is no primary prevention for Docetaxel induced dacryostenosis. The rationale of this randomized double blind interventional study is to investigate the efficacy of corticosteroid versus artificial tears topical eye treatment in patients on a weekly Docetaxel regimen in prevention of dacryostenosis. The dacryotoxic agent Docetaxel in the lacrimal tears will be washed away by the repetitive use of eye drops. In addition, eye drops containing corticosteroids have an anti-inflammatory effect and may further prevent the formation of fibrosis. A new treatment protocol will be investigated. Two different commercially available eye drops will be compared: dexamethasone sodium phosphate (Maxidex®, Alcon) in one eye of the patient and artificial tears (Lacrystat®, Viatris) in the other eye of the same patient. The study period will start with topical eye treatment from day 1 of cycle 1 and will continue during the administration of chemotherapy, with a final analysis at 26 weeks.

Conditions

Epiphora

Keywords

Lacrimal Obstruction; Epiphora

Outcome Measures

Primary Outcomes (2)

• Incidence of dacryostenosis

  20 weeks

• Grading of dacryostenosis

  20 weeks

Secondary Outcomes (1)

• Correlation Docetaxel in lacrimal tear and dacryostenosis

  20 weeks

Study Arms (2)

Lacrystat

PLACEBO COMPARATOR

Lacrystat

Drug: Maxidex; Lacrystat

Maxidex

ACTIVE COMPARATOR

Applying Maxidex

Drug: Maxidex; Lacrystat

Interventions

Maxidex; Lacrystat DRUG

6 times daily, for 20 weeks.

Lacrystat; Maxidex

Eligibility Criteria

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

You may qualify if:

• Patients with locally advanced or metastatic breast cancer receiving weekly Docetaxel chemotherapy with rest weeks in between at regular time intervals. The timing of rest weeks between cycles is not restricted. Examples of allowed regimens are Docetaxel 36 mg/m2 day 1 and 8 every 3 weeks; day 1, 8, 15 every 4 weeks; day 1, 8, 15, 21, 28, 35, 42, 49 every 10 weeks. Dosing and rest weeks can be further modified depending on the clinical situation, but dose intensity should be at least 60 mg/m2 every 3 weeks during the 9 week treatments for eligibility. Combination with other chemotherapy (such as capecitabine) is allowed.
• Capability to administer eye drops (either by patient or companion).
• Written informed consent.
• Age \> 18 y

You may not qualify if:

• Systemic criteria:
• Previous administration of Docetaxel.
• Pregnancy.
• Eye criteria:
• Ocular surface, corneal, conjunctival or eyelid disease.
• Soft contact lens wearing
• Glaucoma
• Lacrimal criteria:
• Hypersecretion of tears: ocular surface, corneal, conjunctival or eyelid disease.
• Functional blockage of lacrimal drainage without anatomical obstruction (facial nerve palsy, displacement of the lower lacrimal punctum from the lacrimal lake, involutional lower eyelid laxity).
• Anatomical obstruction of lacrimal drainage system:

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

Mombaerts

Leuven, 3000, Belgium

Location

MeSH Terms

Conditions

Lacrimal Apparatus Diseases

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Eye Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Ilse Mombaerts, MD, PhD

  Universitaire Ziekenhuizen KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 16, 2005
• First Posted: December 19, 2005
• Study Start: July 1, 2006
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2009
• Last Updated: June 28, 2010

Record last verified: 2005-12

Locations

BE (1)