Clinical Study of Vaginal Lactobacilli and Estriol (Gynoflor®) for Atrophic Vaginitis in Breast Cancer Patients

NCT01370551 | Completed Phase 1 Results

• 1 other identifier: 806109
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 2

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.

Conditions

Atrophic Vaginitis

Outcome Measures

Primary Outcomes (4)

• Serum Concentrations of Estriol (E3)

  Estrogens were analyzed using a highly sensitive gas chromatography-mass spectrometry (GC/MS) method. The lower limits of quantitation (LLOQ) were 10.00 pg/ml for E3, 1.The coefficient of variation (CV, intra-assay variation) was 2.0 % for E3 (calibration range (CR) 10.00-500.00 pg/). The lower limits of quantitation (LLOQ) were 1.00 pg/ml for E2, and 2.00 pg/ml for E1.The coefficient of variation (CV, intra-assay variation) was 4.2 % for E2 (CR 1.00-150.00 pg/ml), and 3.4 % for E1 (CR 2.00-300.00 pg/ml).

  -0.5, 0.5, 1, 2, 3, 4, 6, 8, 24 hours on days 0 and 28

• Calculation of Pharmacokinetic Parameters Estriol: Cmax

  Cmax is the highest measured concentration

  Days 0 and 28

• Calculation of Pharmacokinetic Parameters Estriol: Tmax

  Tmax is the peak time at which the Cmax (maximum concentration) was measured

  Days 0 and 28

• Calculation of Pharmacokinetic Parameters Estriol: Area Under the Curve (AUC)

  Area under the curve from administration to the last measured concentration (AUC0-24)

  Days 0 and 28

Secondary Outcomes (5)

• Baseline / Trough Serum Concentrations of Estriol

  Days 0, 14, 28, 56 and 84

• Vaginal pH

  at all visits during 12 weeks

• Baseline / Trough Serum Concentrations of Luteinizing Hormone (LH)

  Days 0, 14, 28, 56 and 84

• Baseline / Trough Serum Concentrations of Sex Hormone Binding Globulin (SHBG)

  Days 0, 14, 28, 56 and 84

• Baseline / Trough Serum Concentrations of Follicule Stimulating Hormone (FSH)

  Days 0, 14, 28, 56 and 84

Study Arms (1)

Gynoflor

EXPERIMENTAL

Gynoflor vaginal tablets 1/day x 4 weeks, then 3/week for 8 weeks

Drug: Estriol 0.03 mg, lyophylized lactobacillus

Interventions

Estriol 0.03 mg, lyophylized lactobacillus DRUG

Vaginal tablet with lyophilised lactobacilli and 0.03 mg estriol; Once daily for 28 days then 3 times per week for 8 weeks;

Also known as: Gynoflor

Gynoflor

Eligibility Criteria

• Age: 52 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Postmenopausal and age ≥52 with cessation of menses for at least 12 months
• Age 52 - 75 years
• Clinical symptoms of vaginal atrophy
• Vaginal pH \> 5.0
• Karnofsky score ≥80%
• Signed Informed Consent Form together with contractual capability

You may not qualify if:

• Local or systemic use of any other sexual hormones (estrogens, progestins, androgens), 6 months before and during study
• 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
• Local or systemic use of any other anti-infectives, 2 weeks before and during study
• 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
• Known or suspected hypersensitivity or intolerance to the study medications, inclusive their excipients
• Suspicion of or clinically manifest sexually transmitted infections (infections with Neisseria gonorrhoea, Chlamydia trachomatis, Treponema pallidum, genital herpes, Trichomonas vaginalis, genital condylomata, HIV)
• Clinical evidence of vaginal infections requiring extra treatment
• Any infections of the upper genital tract
• Hysterectomy
• Genital haemorrhage of unknown origin
• Malignant or pre-cancerous conditions of the uterus, vulva and/or vagina (PAP smear less than 3 years ago)
• Acute thrombophlebitis, thromboembolic disorders or a history of these disorders in association with previous use of oestrogen preparations
• Abuse of alcohol or drugs
• All chronic illnesses which could influence the absorption, distribution, biotransformation or elimination of the test preparation
• 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

Sponsors & Collaborators

• Medinova AG: lead

Study Sites (2)

University Hospital Leuven

Leuven, Belgium

Location

Department of Obstetrics and Gynaecology, University of Regensburg

Regensburg, Germany

Location

Related Publications (3)

• 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.

  PMID: 24718774 RESULT

• 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.

  PMID: 25427450 RESULT

• 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.

  PMID: 26223323 RESULT

Related Links

• Publication of main results

MeSH Terms

Conditions

Atrophic Vaginitis

Interventions

Estriol

Condition Hierarchy (Ancestors)

Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

The weaknesses of the study were small numbers for testing of some parameters (especially dyspareunia).

Results Point of Contact

• Title: Doerthe Bassfeld
• Organization: Medinova

bassfeld.doerthe@medinova.ch

+41 44 306 1371

Study Officials

• Patrick Neven, Prof. Dr.

  University Hospital Leuven, Belgium

  PRINCIPAL INVESTIGATOR

• Stefan Buchholz, PD Dr.

  Department of Obstetrics and Gynaecology, University of Regensburg, Germany

  PRINCIPAL INVESTIGATOR

• Gilbert Donders, Prof. Dr.

  Femicare, University Hospital, Leuven, Belgium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2011
• First Posted: June 10, 2011
• Study Start: April 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: October 15, 2024
• Results First Posted: October 15, 2024

Record last verified: 2024-10

Locations

DE (1); BE (1)