A Clinical Trial to Assess the Safety of 0.005 % Estriol Vaginal Gel in Hormone Receptor-Positive Postmenopausal Women With Early Stage Breast Cancer in Treatment With Aromatase Inhibitor in the Adjuvant Setting

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02413008
• Date of registration: 01/04/2015
• Prospective Registration: Yes
• Primary sponsor: ITF Research Pharma, S.L.U.
• Public title: A Clinical Trial to Assess the Safety of 0.005 % Estriol Vaginal Gel in Hormone Receptor-Positive Postmenopausal Women With Early Stage Breast Cancer in Treatment With Aromatase Inhibitor in the Adjuvant Setting BLISSAFE
• Scientific title: A Phase II Prospective, Randomized, Double-Blind, Placebo-Controlled and Multi-Centre Clinical Trial to Assess the Safety of 0.005 % Estriol Vaginal Gel in Hormone Receptor-Positive Postmenopausal Women With Early Stage Breast Cancer in Treatment With Aromatase Inhibitor in the Adjuvant Setting
• Date of first enrolment: October 16, 2015
• Target sample size: 61
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02413008
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Spain, Sweden

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Written informed consent prior to beginning specific protocol procedures.

2. Patients must have histological confirmation of breast adenocarcinoma with stage
I-IIIA, documented at a local pathology department.

3. The breast tumors must be estrogen-receptor positive and/or progesterone receptor
positive (=1% of stained tumor cells by Immunohistochemistry (IHC) as determined by
the local laboratory) with any Human Epidermal Growth Factor Receptor 2(HER2) status.

4. Postmenopausal status defined as: 12 months of spontaneous amenorrhea or 6 months of
spontaneous amenorrhea with serum FSH levels > 40 Milli-international units per
milliliter (mIU/ml) or 6 weeks postsurgical bilateral oophorectomy with or without
hysterectomy.

5. Patient must be receiving the non-steroidal aromatase inhibitors anastrozole or
letrozole as breast cancer treatment in the adjuvant setting for a minimum of 6
months.

6. Women suffering from moderate to severe vaginal dryness according to the FDA
guidelines for drug development in postmenopausal women (Center for Drug Evaluation
and Research, (CDER) Jan 2003). A moderate symptom will be considered if the symptom
is present, bothersome and annoying, and a severe symptom will be considered if the
symptom is present, bothersome and annoying, and interferes with the normal patient
activity.

7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.

8. Adequate bone marrow as defined by the following laboratory values:

1. Absolute Neutrophil Count (ANC) = 1.5 x 109/L.

2. Platelets (plt) = 100 x 109/L.

3. Hemoglobin (Hgb) = 10 g/dl.

9. Patient has adequate organ function as defined by the following laboratory values:

1. Serum creatinine = 1.5 x Upper Limit of Normal (ULN).

2. Bilirubin = 1.5 × ULN.

3. Alkaline phosphatase = 2 × ULN.

4. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) = 2 × ULN.

10. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
tests and other study procedures.

Exclusion Criteria:

1. Stage IIIB-IV breast cancer or bilateral breast cancer.

2. Treatment with any other current anti-tumoral therapy (chemotherapy, anti-Her2…etc)
besides the NSAI. Pamidronate or Alendronate are permitted.

3. Prior history of other malignancy within 5 years of study entry, aside from
non-melanoma skin cancer or carcinoma-in-situ of the uterine cervix adequately
treated.

4. Postmenopausal uterine bleeding. Vaginal bleeding of unknown etiology.

5. Patients with endometrial thickness equal to or greater than 4 mm measured by
transvaginal ultrasound.

6. Patients who have received any type of vulvovaginal treatment in the 15 days prior to
the start of the study.

7. Use of any hormone, natural (phytoestrogens) or herbal products for the treatment of
menopausal symptoms within the last 3 months.

8. Current or previous history of thromboembolic disease or coagulopathies.

9. Severe cardiovascular or respiratory diseases in the previous 6 months.

10. Renal Impairment.

11. Hepatitis B and/or hepatitis C carriers (unless with normal hepatic function).

12. Known human immunodeficiency virus infection.

13. Known hypersensitivity to NSAI.

14. Other severe acute or chronic medical or psychiatric condition, or laboratory
abnormality that would impart, in the judgment of the investigator, excess risk
associated with study participation or study drug administration, or which, in the
judgment of the investigator, would make the patient inappropriate for entry into this
study.

15. Previous investigational treatment for any condition or participation in any clinical
trial within 4 weeks of inclusion date.



Age minimum: N/A
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Vaginal Atrophy

Intervention(s)

Drug: Placebo

Drug: estriol

Primary Outcome(s)

Variation in Serum Levels of Follicle Stimulating Hormone (FSH) [Time Frame: from baseline to 12 weeks of treatment]

Secondary Outcome(s)

Changes in Total Score of Signs of Vaginal Atrophy Between Week 3 and Week 12 to Baseline [Time Frame: week 3 and week 12 vs baseline]

Changes in Vaginal Dryness [Time Frame: week 3 and week 12 vs baseline]

Variation in Serum Levels of Luteinizing Hormone (LH) [Time Frame: Change from baseline to week 1, week 3, week 8 and week 12]

Changes in Fragility of the Mucosa [Time Frame: Week 3 and Week 12 vs Baseline] [Time Frame: from baseline to week 3 and 12]

Changes in Vaginal Mucosa With Flattening of Folds or Thinning [Time Frame: week 3 and week 12 vs baseline]

Changes in Vaginal pH Between Baseline and Week 3 and Week 12 [Time Frame: week 3 and week 12 vs baseline]

Changes in Dyspareunia [Time Frame: week 3 and week 12 vs baseline]

Change in Pruritus or Itching From Baseline to Week 3 and Week 12 [Time Frame: Change from baseline to week 3 and week 12]

Changes in Total Score of Symptoms of Vaginal Atrophy [Time Frame: week 3 and week 12 vs baseline]

Variation in Serum Levels of FSH at Week 1, Week 3 and Week 8 [Time Frame: Change from baseline to week 1, week 3 and week 8]

Variation in Plasma Levels of Estriol [Time Frame: Change from baseline to week 1, week 3, week 8 and week 12]

Changes in Dryness of the Mucosa [Time Frame: week 3 and week 12 vs baseline]

Variation in Plasma Levels of Estradiol [Time Frame: Change from baseline to week 1, week 3, week 8 and week 12]

Changes in Vaginal Maturation Value [Time Frame: week 3 and week 12 vs baseline]

Variation in Plasma Levels of Estrona [Time Frame: Change from baseline to week 1, week 3, week 8 and week 12]

Secondary ID(s)

ITFE-2026-C10

2014-004517-84

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Spanish Breast Cancer Research Group

Results

• Results available: Yes
• Date Posted: 05/08/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02413008