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
Condition: Vaginal Atrophy
MeSH terms: Atrophy
Intervention: estriol; Placebo
Intervention description: 0.005% estriol vaginal gel; placebo vaginal gel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 61.0
Sex: Female
Healthy volunteers: No
Keywords: vaginal atrophy; breast cancer; vaginal dryness; aromatase inhibitor

Summary:

      This is a phase II, prospective, randomized, double-blind, placebo-controlled, international
      (Spain and Sweden) and multicentre study to explore the safety of 0.005% estriol vaginal gel
      in women with early stage breast cancer in treatment with Non-Steroidal Aromatase Inhibitors
      (NSAIs) in the adjuvant setting and symptoms of vaginal atrophy.
    

Eligibility 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.