Clinical trial NCT01370551: Clinical Study of Vaginal Lactobacilli and Estriol (Gynoflor®) for Atrophic Vaginitis in Breast Cancer Patients
Official title: A Clinical Study of Pharmacokinetics, Efficacy and Safety of Vaginal Application of Lyophilised Lactobacilli and 0.03 mg Estriol (Gynoflor®) on Atrophic Vaginitis in Postmenopausal Breast Cancer Patients Treated With Aromatase Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atrophic Vaginitis
Lead sponsor: Medinova AG
Sponsor class: INDUSTRY
First posted: 2011-06-10
Enrollment: 16
Sex: FEMALE
Minimum age (years): 52
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the long term safety and efficacy of the vaginal application of Gynoflor®, an extremely low dosed estrogen therapy with lactobacilli, on atrophic vaginitis in postmenopausal breast cancer patients who have been treated with aromatase inhibitors.

Detailed description: Two center phase I pharmacokinetic study assessed circulating estrogens in breast cancer patients on a non-steroidal aromatase inhibitor (NSAI) with vaginal atrophy using vaginal ultra-low-dose 0.03 mg estriol (E3) and Lactobacillus combination vaginal tablets (Gynoflor). 16 women on nonsteroidal aromatase inhibitor with severe vaginal atrophy applied a daily vaginal tablet of Gynoflor for 28 days followed by a maintenance therapy of 3 tablets weekly for 8 weeks.

Eligibility criteria: Inclusion Criteria:

1. Patients with breast cancer on non-steroidal AI therapy (AI therapy start at least 6 months ago, and are scheduled to receive them during the study)
2. Postmenopausal and age ≥52 with cessation of menses for at least 12 months
3. Age 52 - 75 years
4. Clinical symptoms of vaginal atrophy
5. Vaginal pH \> 5.0
6. Karnofsky score ≥80%
7. Signed Informed Consent Form together with contractual capability

Exclusion Criteria:

1. Local or systemic use of any other sexual hormones (estrogens, progestins, androgens), 6 months before and during study
2. Local or systemic use of phytoestrogens or products known for or taken to improve vaginal mucosal function, risk of vaginal infections, or vulvovaginal symptoms, 4 weeks before and during study
3. Local or systemic use of any other anti-infectives, 2 weeks before and during study
4. Use of any other vaginal medication, vaginal rinses and/or moisturizers, gels containing xylocain or other analgesic products to decrease pain during intercourse, 1 week before and during study
5. Known or suspected hypersensitivity or intolerance to the study medications, inclusive their excipients
6. Suspicion of or clinically manifest sexually transmitted infections (infections with Neisseria gonorrhoea, Chlamydia trachomatis, Treponema pallidum, genital herpes, Trichomonas vaginalis, genital condylomata, HIV)
7. Clinical evidence of vaginal infections requiring extra treatment
8. Any infections of the upper genital tract
9. Hysterectomy
10. Genital haemorrhage of unknown origin
11. Malignant or pre-cancerous conditions of the uterus, vulva and/or vagina (PAP smear less than 3 years ago)
12. Acute thrombophlebitis, thromboembolic disorders or a history of these disorders in association with previous use of oestrogen preparations
13. Abuse of alcohol or drugs
14. All chronic illnesses which could influence the absorption, distribution, biotransformation or elimination of the test preparation
15. Patient has a condition or is in a situation which, in the investigator's opinion, may put the patient in significant risk, may confound the study result, or may interfere significantly with the patient's participation in the study
16. BMI lower than 18.5 or higher than 30
17. Patient on steroidal AIs (aromasin)
18. Vulvo-dermatological conditions (like Lichen sclerosus, Lichen rubrus, Psoriasis)
19. Genital prolapses
20. Endometriosis
21. Use of antibiotics or chemotherapeuticals which are harmful to lactobacilli
22. Participation of patient in another investigational drug study, with the exception of treatment optimisation studies with non-steroidal aromatase inhibitors (AI)s
23. Previous participation in this study
24. Patient is a relative of, or staff directly reporting to the investigator
25. Patient is an employee of the sponsor

Primary outcomes:
measure: Serum Concentrations of Estriol (E3)
timeFrame: -0.5, 0.5, 1, 2, 3, 4, 6, 8, 24 hours on days 0 and 28
measure: Calculation of Pharmacokinetic Parameters Estriol: Cmax
timeFrame: Days 0 and 28
measure: Calculation of Pharmacokinetic Parameters Estriol: Tmax
timeFrame: Days 0 and 28
measure: Calculation of Pharmacokinetic Parameters Estriol: Area Under the Curve (AUC)
timeFrame: Days 0 and 28
Secondary outcomes:
measure: Baseline / Trough Serum Concentrations of Estriol
timeFrame: Days 0, 14, 28, 56 and 84
measure: Vaginal pH
timeFrame: at all visits during 12 weeks
measure: Baseline / Trough Serum Concentrations of Luteinizing Hormone (LH)
timeFrame: Days 0, 14, 28, 56 and 84
measure: Baseline / Trough Serum Concentrations of Sex Hormone Binding Globulin (SHBG)
timeFrame: Days 0, 14, 28, 56 and 84
measure: Baseline / Trough Serum Concentrations of Follicule Stimulating Hormone (FSH)
timeFrame: Days 0, 14, 28, 56 and 84
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Regensburg
country: Germany
facility: Department of Obstetrics and Gynaecology, University of Regensburg
Study officials:
affiliation: University Hospital Leuven, Belgium
name: Patrick Neven, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Obstetrics and Gynaecology, University of Regensburg, Germany
name: Stefan Buchholz, PD Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Femicare, University Hospital, Leuven, Belgium
name: Gilbert Donders, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Donders G, Neven P, Moegele M, Lintermans A, Bellen G, Prasauskas V, Grob P, Ortmann O, Buchholz S. Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor((R))) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study. Breast Cancer Res Treat. 2014 Jun;145(2):371-9. doi: 10.1007/s10549-014-2930-x. Epub 2014 Apr 10.
citation: Buchholz S, Mogele M, Lintermans A, Bellen G, Prasauskas V, Ortmann O, Grob P, Neven P, Donders G. Vaginal estriol-lactobacilli combination and quality of life in endocrine-treated breast cancer. Climacteric. 2015 Apr;18(2):252-9. doi: 10.3109/13697137.2014.991301. Epub 2015 Jan 20.
citation: Donders G, Bellen G, Neven P, Grob P, Prasauskas V, Buchholz S, Ortmann O. Effect of ultra-low-dose estriol and lactobacilli vaginal tablets (Gynoflor(R)) on inflammatory and infectious markers of the vaginal ecosystem in postmenopausal women with breast cancer on aromatase inhibitors. Eur J Clin Microbiol Infect Dis. 2015 Oct;34(10):2023-8. doi: 10.1007/s10096-015-2447-1. Epub 2015 Jul 30.