Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06654570
Status:
COMPLETED
Last Update Posted:
None
First Post:
2024-10-21
Brief Title:
Effects of Vaginal Estrogen on Serum Estradiol During Aromatase Inhibitor Therapy in Breast Cancer Patients with Vulvovaginal Atrophy a Prospective Trial
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Effects of Vaginal Estrogen on Serum Estradiol During Aromatase Inhibitor Therapy in Breast Cancer Patients with Vulvovaginal Atrophy a Prospective Trial
Status:
COMPLETED
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Purpose This study aimed to analyze changes in serum estradiol E2 levels during concurrent vaginal estradiol therapy and adjuvant letrozole in postmenopausal breast cancer BC patients with vulvovaginal atrophy VVA Secondary objectives included assessing the effects of therapy on vaginal atrophy quality of life QoL and menopause-related symptoms
Methods Postmenopausal patients undergoing adjuvant letrozole therapy and experiencing VVA symptoms were treated with vaginal estradiol for 12 weeks Gynecologic examination and symptom screening were conducted at baseline and after 12 weeks Serum E2 levels were analyzed at baseline and at two four eight and 12 weeks E2 levels were measured using both a routine liquid chromatography-tandem mass spectrometry LC-MSMS method and a highly sensitive hsE2-MS LC-MSMS method
Methods Postmenopausal patients undergoing adjuvant letrozole therapy and experiencing VVA symptoms were treated with vaginal estradiol for 12 weeks Gynecologic examination and symptom screening were conducted at baseline and after 12 weeks Serum E2 levels were analyzed at baseline and at two four eight and 12 weeks E2 levels were measured using both a routine liquid chromatography-tandem mass spectrometry LC-MSMS method and a highly sensitive hsE2-MS LC-MSMS method
Detailed Description:
The study was conducted between November 2020 and May 2024 at the Comprehensive Cancer Center Helsinki University Hospital Finland Eligible patients were postmenopausal women 50 years old with early-stage hormone receptor-positive BC treated with adjuvant letrozole for at least six months and developed symptoms of AV during this period Exclusion criteria included premenopausal status recent use of local estrogen therapy within the previous three months irregular use of letrozole and metastatic disease
VVA diagnosis was based on patient-reported symptoms with gynecologic examinations including speculum examination with transvaginal sonography performed for all participants at baseline Vaginal Pap smears were used to determine the vaginal maturation index VMI by assessing the proportions of parabasal intermediate and superficial cells in the vaginal wall along with other cytological findings according to the Bethesda System for cervical cytology Vaginal pH was measured using litmus paper placed on the vaginal wall until moistened serving as an indicator of VVA
Eligible patients were treated with Vagifem 17β-estradiol hemihydrate 10 μg vaginal tablets for 12 weeks Patients were instructed to insert one vaginal tablet daily using the provided applicator for 14 consecutive days followed by one tablet twice weekly Monday and Thursday evenings Blood samples were collected at baseline prior to the initiation of study treatment and at two four eight and 12 weeks thereafter within 24 to 60 hours of vaginal tablet administration Serum was separated by centrifugation within 1 hour of collection and the samples were stored at -80C until analysis
Patients completed the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires to assess QoL with higher scores indicating better QoL or less QoL related symptoms and the Womens Health Questionnaire WHQ where higher scores indicated greater distress and dysfunction at baseline and after 12 weeks Menopause-related symptoms were assessed using a structured 19-item questionnaire while sexual function was evaluated with the McCoy Female Sexuality Questionnaire which was completed by only half of the patients due to its limitation to sexually active participants Higher scores on both questionnaires indicated greater severity or frequency of symptoms
A follow-up gynecologic examination and oncology consultation were conducted at the end of the study to assess the patients response to topical estradiol therapy Patients who maintained serum E2 levels below LLOQ 5 pmolL and benefited from the therapy were considered for continued treatment off-study
The primary objective was to analyze changes in serum E2 levels using two LC-MSMS methods during concurrent adjuvant AI therapy and intravaginal estradiol treatment Serum E2 levels were measured using both a routine LC-MSMS method Sciex Citrine Triple Quad LC-MSMS system E2-MS HUSLAB LLOQ 10 pmolL and a highly sensitive LC-MSMS method hsE2-MS LLOQ 5 pmolL CV 20 LOD 1 pmolL The hsE2-MS method allowed for the detection of very low serum E2 concentrations even below the LLOQ within the range of 1-5 pmolL providing a precise assessment of the effect of letrozole and vaginal estrogen on E2 levels
The intervention was considered unsuccessful if persistent elevation of E2 5pmolL in two consecutive tests was observed after treatment initiation
The local ethics committee of the Helsinki University Hospital approved the study protocol No 118 Informed consent was obtained from all participants included in the study The trial was registered in the Helsinki and Uusimaa Hospital District Clinical Trials Register with EudraCT Number 2019-001234-34
VVA diagnosis was based on patient-reported symptoms with gynecologic examinations including speculum examination with transvaginal sonography performed for all participants at baseline Vaginal Pap smears were used to determine the vaginal maturation index VMI by assessing the proportions of parabasal intermediate and superficial cells in the vaginal wall along with other cytological findings according to the Bethesda System for cervical cytology Vaginal pH was measured using litmus paper placed on the vaginal wall until moistened serving as an indicator of VVA
Eligible patients were treated with Vagifem 17β-estradiol hemihydrate 10 μg vaginal tablets for 12 weeks Patients were instructed to insert one vaginal tablet daily using the provided applicator for 14 consecutive days followed by one tablet twice weekly Monday and Thursday evenings Blood samples were collected at baseline prior to the initiation of study treatment and at two four eight and 12 weeks thereafter within 24 to 60 hours of vaginal tablet administration Serum was separated by centrifugation within 1 hour of collection and the samples were stored at -80C until analysis
Patients completed the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires to assess QoL with higher scores indicating better QoL or less QoL related symptoms and the Womens Health Questionnaire WHQ where higher scores indicated greater distress and dysfunction at baseline and after 12 weeks Menopause-related symptoms were assessed using a structured 19-item questionnaire while sexual function was evaluated with the McCoy Female Sexuality Questionnaire which was completed by only half of the patients due to its limitation to sexually active participants Higher scores on both questionnaires indicated greater severity or frequency of symptoms
A follow-up gynecologic examination and oncology consultation were conducted at the end of the study to assess the patients response to topical estradiol therapy Patients who maintained serum E2 levels below LLOQ 5 pmolL and benefited from the therapy were considered for continued treatment off-study
The primary objective was to analyze changes in serum E2 levels using two LC-MSMS methods during concurrent adjuvant AI therapy and intravaginal estradiol treatment Serum E2 levels were measured using both a routine LC-MSMS method Sciex Citrine Triple Quad LC-MSMS system E2-MS HUSLAB LLOQ 10 pmolL and a highly sensitive LC-MSMS method hsE2-MS LLOQ 5 pmolL CV 20 LOD 1 pmolL The hsE2-MS method allowed for the detection of very low serum E2 concentrations even below the LLOQ within the range of 1-5 pmolL providing a precise assessment of the effect of letrozole and vaginal estrogen on E2 levels
The intervention was considered unsuccessful if persistent elevation of E2 5pmolL in two consecutive tests was observed after treatment initiation
The local ethics committee of the Helsinki University Hospital approved the study protocol No 118 Informed consent was obtained from all participants included in the study The trial was registered in the Helsinki and Uusimaa Hospital District Clinical Trials Register with EudraCT Number 2019-001234-34
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None