This is a multicenter, open-label, single-arm study of prophylaxis for Dato-DXd-related stomatitis in eligible patients with metastatic or inoperable locally recurrent breast cancer or locally advanced or metastatic Epidermal Growth Factor Receptor-Mutated (EGFRm) non-small cell lung cancer.
The purpose of this Phase IV study is to describe the incidence and severity of Dato-DXd treatment-emergent grade ≥ 2 stomatitis in participants receiving prophylactic dexamethasone mouthwash within the first 12 weeks of study treatment (ie, Dato-DXd dosing). The study will enroll an estimated 100 participants across approximately 35 sites in the U.S. Enrollment of participants is planned to occur over approximately 18 months, with a minimum of 12 weeks of follow-up for each participant after the first Dato-DXd dose. This study has one arm, and the study population will consist of 2 independent cohorts (approximately 50 participants in each cohort): * Breast cohort (Cohort 1) * Lung cohort (Cohort 2) Participants will receive the study intervention, dexamethasone mouthwash, throughout the duration of their standard of care treatment with Dato-DXd.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
100
Dexamethasone steroid-based oral solution, comprised of 0.5 milligrams per 5mL of alcohol-free dexamethasone.
Commercially available Dato-DXd is prescribed and administered to participants according to standard of care
Research Site
Tucson, Arizona, United States
Research Site
Hot Springs, Arkansas, United States
Research Site
Little Rock, Arkansas, United States
Research Site
Duarte, California, United States
Research Site
Glendale, California, United States
Research Site
Lakewood, California, United States
Research Site
Torrance, California, United States
Research Site
Athens, Georgia, United States
Research Site
Park Ridge, Illinois, United States
Research Site
Fort Wayne, Indiana, United States
...and 10 more locations
Incidence and severity of Dato-DXd treatment-emergent grade ≥ 2 stomatitis in patients receiving prophylactic dexamethasone mouthwash within first 12 weeks of study treatment
Incidence is defined as the proportion of participants who develop National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 grade ≥ 2 stomatitis accompanied by either a Normalcy of Diet Subscale score ≤ 50 and/or a Numeric Rating Scale (NRS) oral-pain score of 7 on 2 consecutive days or 8, 9, or 10 on any one day. Severity will be based on the highest NCI-CTCAE v5.0 grade of stomatitis experienced by each participant. CTCAE displays Grades 1-5 with descriptions of severity for each adverse event (AE). Grade 1 for mild symptoms and Grade 5 for death related to AE. The Normalcy of Diet Subscale assesses the degree to which a patient can eat a normal diet and drink liquids. The scale is a ranking of 10 food categories, from easy-to-eat to difficult-to-eat. The Numeric Rating Scale is a scale for self-reporting of pain. Scores range from 0-10, with higher scores meaning the worst pain possible (0=no pain to 10=worst possible pain).
Time frame: From date of first dose of study treatment until 12 weeks after date of first dose of study treatment
Incidence and severity of Dato-DXd treatment-emergent grade ≥ 2 stomatitis
This will be determined using the composite stomatitis definition in the primary outcome. Will be repeated within 6 weeks and within 9 weeks of study treatment.
Time frame: From date of first dose of study treatment until 6 and 9 weeks after date of first dose of study treatment
Incidence and severity of treatment-emergent stomatitis overall, by maximum CTCAE grade, and CTCAE grade ≥ 2
This will be determined using stomatitis CTCAE grade only. Will be analysed at 6, 9 and 12 weeks.
Time frame: From date of first dose of study treatment until 6, 9 and 12 weeks after date of first dose of study treatment
Time to onset of grade ≥ 2 stomatitis
The time (in days) from the date of the first dose of Dato-DXd to the date of first onset to a grade ≥ 2 stomatitis event. The measure of primary interest is median time to onset.
Time frame: From date of first dose until earliest of diagnosis of grade ≥2 stomatitis, Dato-DXD discontinuation and death, whichever occurs first, assessed up to approximately 21 months
Time to resolution of Dato-DXd-related grade ≥ 2 stomatitis
Number of days from the date of onset of stomatitis grade ≥ 2 until the earliest date of event resolved or reduced in severity to grade 1. The measure of primary interest is median time to resolution.
Time frame: From date of diagnosis of grade ≥2 stomatitis until the earliest date of event resolved or reduced in severity to grade 1, assessed up to approximately 21 months
Proportion of participants with a dose modification for Dato-DXd due to stomatitis
Dose modification is defined as dose reduction, delay, or discontinuation due to stomatitis Treatment-Emergent Adverse Event (TEAE).
Time frame: From date of first dose until earliest of Dato-DXD discontinuation and death, assessed up to approximately 21 months
Participant adherence to dexamethasone mouthwash
Adherence to dexamethasone mouthwash will be assessed by cohort using the Daily Activities Diary. The measure of primary interest is the median number of swished mouthwashes per day.
Time frame: From date of first dose of study treatment until 12 weeks after date of first dose of study treatment
Safety and tolerability of Dato-DXd in participants receiving prophylactic dexamethasone mouthwash
Safety and tolerability will be evaluated by cohort in terms of AEs (graded by NCI-CTCAE v5.0) and in terms of the following: * Incidence and severity of TEAEs and Serious Adverse Events (SAEs), including oral infections (such as fungal infections) associated with the use of the dexamethasone mouthwash * Eastern Cooperative Oncology Group (ECOG) performance status * Vital signs and physical examination * Clinical chemistry, hematology, urinalysis, and coagulation assessments * Use of antifungal medication for treating dexamethasone-related fungal infection.
Time frame: From date of first dose of study intervention until 28 days after the last dose (Safety Follow-up), approximately 21 months
AstraZeneca Clinical Study Information Center
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