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Vaginal AtrophyPhase 2BLISSAFENCT02413008

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

A Phase 2 study testing estriol in people with Vaginal Atrophy, run by ITF Research Pharma, S.L.U. at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Any age, women only
Conditions the study is for
Vaginal Atrophy
What is being tested?
estriol
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
61 participants
Where
6 sitesin 2 countries
Study dates
16 Oct 2015to 10 Feb 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Written informed consent prior to beginning specific protocol procedures.
  • Patients must have histological confirmation of breast adenocarcinoma with stage I-IIIA, documented at a local pathology department.
  • 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.
  • 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.
  • 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.
  • 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.
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  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  • Adequate bone marrow as defined by the following laboratory values:
  • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L.
  • Platelets (plt) ≥ 100 x 109/L.
  • Hemoglobin (Hgb) ≥ 10 g/dl.
  • Patient has adequate organ function as defined by the following laboratory values:
  • Serum creatinine ≤ 1.5 x Upper Limit of Normal (ULN).
  • Bilirubin ≤ 1.5 × ULN.
  • Alkaline phosphatase ≤ 2 × ULN.
  • Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2 × ULN.
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Who cannot join

  • Stage IIIB-IV breast cancer or bilateral breast cancer.
  • Treatment with any other current anti-tumoral therapy (chemotherapy, anti-Her2…etc) besides the NSAI. Pamidronate or Alendronate are permitted.
  • 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.
  • Postmenopausal uterine bleeding. Vaginal bleeding of unknown etiology.
  • Patients with endometrial thickness equal to or greater than 4 mm measured by transvaginal ultrasound.
  • Patients who have received any type of vulvovaginal treatment in the 15 days prior to the start of the study.
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  • Use of any hormone, natural (phytoestrogens) or herbal products for the treatment of menopausal symptoms within the last 3 months.
  • Current or previous history of thromboembolic disease or coagulopathies.
  • Severe cardiovascular or respiratory diseases in the previous 6 months.
  • Renal Impairment.
  • Hepatitis B and/or hepatitis C carriers (unless with normal hepatic function).
  • Known human immunodeficiency virus infection.
  • Known hypersensitivity to NSAI.
  • 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.
  • Previous investigational treatment for any condition or participation in any clinical trial within 4 weeks of inclusion date.

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

Spain5 sites
  • For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.

    A Coruña, 15006

  • For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.

    Jaén, 23007

  • For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.

    L'Hospitalet de Llobregat, Barcelona, 08908

  • For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.

    Madrid, 28050

  • For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.

    Valencia, 46010

Other trials in Spain

Sweden1 site
  • For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.

    Stockholm, 171 77

Other trials in Sweden

About this study

Official 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

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.

Read the detailed description

This is a phase II, prospective, randomized, double-blind, placebo-controlled, international (Spain and Sweden) and multicentre study.

In the setting of postmenopausal hormone receptor positive breast cancer, treatment with aromatase inhibitors (AIs) is the most effective and well-studied therapy. Vaginal dryness is one of the most frequently reported symptom caused by this adjuvant therapy which may lead to a reduced adherence in breast cancer women.

This study will explore the safety of 0.005% estriol vaginal gel in this oncological context, to demonstrate that this medicinal product is a safe option to treat the vaginal atrophy caused by AIs, without a clinically relevant influence in gonadotropins or systemic estrogen levels.

The main objective is to evaluate the levels of Follicle Stimulating Hormone (FSH) after treatment with 0.005% estriol vaginal gel in hormone receptor-positive postmenopausal women with early stage breast cancer in treatment with Non-Steroidal Aromatase Inhibitors (NSAIs) in the adjuvant setting and symptoms of vaginal atrophy.

Conditions
Vaginal Atrophy
Being tested
estriol, Placebo
Keywords
vaginal atrophy, breast cancer, vaginal dryness, aromatase inhibitor
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • estriolDrug

    Also called Blissel (estriol), Gelistrol (estriol)

    0.005% estriol vaginal gel

  • PlaceboDrug

    placebo vaginal gel

Study groups in NCT02413008
Study groupRoleWhat they receive
0.005% estriol vaginal gelExperimentalRoute: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration
Receives: Drug: estriol
placebo vaginal gelPlacebo comparatorRoute: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel. Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Variation in Serum Levels of Follicle Stimulating Hormone (FSH)

    Change from Baseline (mean screening-baseline) to Week 12 in Serum Levels of Follicle Stimulating Hormone (FSH) compare to natural physiological variability (screening-baseline variation)

    Measured: from baseline to 12 weeks of treatment

Secondary outcomes (15)
  1. Variation in Serum Levels of FSH at Week 1, Week 3 and Week 8

    Change from Baseline (mean screening-baseline) to Week 1, Week 3 and Week 8 in Serum Levels of Follicle Stimulating Hormone (FSH) compare to natural physiological variability ( screening-baseline variation)

    Measured: Change from baseline to week 1, week 3 and week 8

  2. Variation in Serum Levels of Luteinizing Hormone (LH)

    Change from (mean screening-baseline) in plasma levels of LH to Week 1, Week 3, Week 8 and Week 12 in Serum Levels of LH compare to natural physiological variability ( screening-baseline variation)

    Measured: Change from baseline to week 1, week 3, week 8 and week 12

  3. Variation in Plasma Levels of Estriol

    Change in plasma levels of estriol at weeks 1, 3, 8 and 12 compared to baseline

    Measured: Change from baseline to week 1, week 3, week 8 and week 12

  4. Variation in Plasma Levels of Estradiol

    Change in plasma levels of estradiol at weeks 1, 3, 8 and 12 compared to baseline.

    Measured: Change from baseline to week 1, week 3, week 8 and week 12

  5. Variation in Plasma Levels of Estrona

    Change in plasma levels of estrona at weeks 1, 3, 8 and 12 compared to baseline.

    Measured: Change from baseline to week 1, week 3, week 8 and week 12

  6. Changes in Vaginal pH Between Baseline and Week 3 and Week 12

    Measurement of vaginal pH on the vaginal secretion using a reactive strip and compare pH value between baseline and the diferent timepoints

    Measured: week 3 and week 12 vs baseline

  7. Changes in Dyspareunia

    Changes in dyspareunia from baseline to week 3 and week 12 Each symptom will be scored in a numeric scale from 0 to 3, as shown 0 Absence. The symptom is not present

    1. The symptom is of mild intensity, without interfering in the patient's activity
    2. The symptom is of moderate intensity, causing obvious discomfort to the patient
    3. The symptom is stated as very irritating and severe in intensity

    Measured: week 3 and week 12 vs baseline

  8. Change in Pruritus or Itching From Baseline to Week 3 and Week 12

    Change in pruritus or itching from baseline to week 3 and week 12

    Each symptom will be scored in a numeric scale from 0 to 3, as shown below:

    0 Absence. The symptom is not present

    1. The symptom is of mild intensity, without interfering in the patient's activity
    2. The symptom is of moderate intensity, causing obvious discomfort to the patient
    3. The symptom is stated as very irritating and severe in intensity

    Measured: Change from baseline to week 3 and week 12

  9. Changes in Vaginal Dryness

    Change in vaginal dryness puntuation score from baseline to w3 and w12

    Each symptom will be scored in a numeric scale from 0 to 3, as shown below:

    0 Absence. The symptom is not present

    1. The symptom is of mild intensity, without interfering in the patient's activity
    2. The symptom is of moderate intensity, causing obvious discomfort to the patient
    3. The symptom is stated as very irritating and severe in intensity

    Measured: week 3 and week 12 vs baseline

  10. Changes in Total Score of Symptoms of Vaginal Atrophy

    Changes in Symptoms of vaginal atrophy (vaginal dryness, dyspareunia and pruritus) at week 3 and week 12 vs baseline.

    Each symptom will be scored in a numeric scale from 0 to 3, as shown below:

    0 Absence. The symptom is not present

    1. The symptom is of mild intensity, without interfering in the patient's activity
    2. The symptom is of moderate intensity, causing obvious discomfort to the patient
    3. The symptom is stated as very irritating and severe in intensity A Global Symptoms Score will be calculated by summing the intensities of all the three symptoms of vaginal atrophy in a certain time point, thus ranging between 0 and 9.

    Measured: week 3 and week 12 vs baseline

  11. Changes in Dryness of the Mucosa

    It will be scored by the investigator on a numerical scale in accordance with their presence and degree of severity as follows:

    0 Absence. The sign is not present.

    1. The sign is present and is considered a mild alteration
    2. The sign is present and is considered a moderate alteration
    3. The sign is present and is considered a severe alteration

    Measured: week 3 and week 12 vs baseline

  12. Changes in Fragility of the Mucosa [Time Frame: Week 3 and Week 12 vs Baseline]

    It will be scored by the investigator on a numerical scale in accordance with their presence and degree of severity as follows:

    0 Absence. The sign is not present.

    1. The sign is present and is considered a mild alteration
    2. The sign is present and is considered a moderate alteration
    3. The sign is present and is considered a severe alteration

    Measured: from baseline to week 3 and 12

  13. Changes in Vaginal Mucosa With Flattening of Folds or Thinning

    It will be scored by the investigator on a numerical scale in accordance with their presence and degree of severity as follows:

    0 Absence. The sign is not present.

    1. The sign is present and is considered a mild alteration
    2. The sign is present and is considered a moderate alteration
    3. The sign is present and is considered a severe alteration

    Measured: week 3 and week 12 vs baseline

  14. Changes in Total Score of Signs of Vaginal Atrophy Between Week 3 and Week 12 to Baseline

    The signs evaluated Will be the following: vaginal mucosa with flattening of folds or thinning, dryness of the mucosa and Fragility of the mucosa.

    It will be scored by the investigator on a numerical scale in accordance with their presence and degree of severity as follows:

    0 Absence. The sign is not present.

    1. The sign is present and is considered a mild alteration
    2. The sign is present and is considered a moderate alteration
    3. The sign is present and is considered a severe alteration A Total Signs Score will be calculated by summing the intensities of all the three signs of vaginal atrophy in a certain time point, thus ranging between 0 and 9.

    Measured: week 3 and week 12 vs baseline

  15. Changes in Vaginal Maturation Value

    Vaginal cytology sample to evaluate the vaginal Maturation Value. For the cytologic evaluation, the number of parabasal, intermediate and superficial cells will be calculated in duplicate on 100 consecutive cells of vaginal cytology. The average of the two percentages obtained for each cell type will be calculated, which will serve to determine the maturation value (MV) based on the following formula:

    0.2 x (% parabasal) + 0.6 x (% intermediate) + 1.0 x (% superficial).

    Measured: week 3 and week 12 vs baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Apr 2015 (estimated)
  2. Study start16 Oct 2015
  3. Primary completion10 Feb 2017
  4. Study completion10 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02413008
Sponsor's protocol ID
ITFE-2026-C10
Other IDs
2014-004517-84, 2014
Acronym
BLISSAFE
Status last verified
Jun 2019
First submitted
1 Apr 2015
Last updated
5 Aug 2019
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Sanchez-Rovira P, Hirschberg AL, Gil-Gil M, Bermejo-De Las Heras B, Nieto-Magro C. A Phase II Prospective, Randomized, Double-Blind, Placebo-Controlled and Multicenter 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. Oncologist. 2020 Dec;25(12):e1846-1854. doi: 10.1634/theoncologist.2020-0417. Epub 2020 Jun 9.

    PubMed 32459035

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing estriol in people with Vaginal Atrophy, run by ITF Research Pharma, S.L.U. at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Spain, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Variation in Serum Levels of Follicle Stimulating Hormone (FSH) (time frame: from baseline to 12 weeks of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02413008, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2019.

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