Estrogen vs Moisturizer for Vaginal Dryness in Breast Cancer Patients

(REVIVE Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Polly Niravath, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Polly A. Niravath, MD

Must be taking: Adjuvant AI therapy

Must not be taking: Exogenous estrogen

Disqualifiers: Current vaginal infection, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial compares a hormone-releasing ring and a moisturizing cream for treating vaginal dryness in breast cancer patients. It focuses on post-menopausal women undergoing specific cancer treatments who suffer from vaginal dryness. The hormone ring works by adding estrogen locally, while the cream provides moisture without hormones.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you must not use any additional estrogen during the study. You can continue using non-estrogen lubricants.

What data supports the effectiveness of the treatment for vaginal dryness in breast cancer patients?

Research shows that both local estrogen therapy and non-hormonal vaginal moisturizers like Replens can effectively increase vaginal moisture and improve symptoms of vaginal dryness. However, while estrogen treatments provide more sustained benefits, non-hormonal moisturizers may only offer temporary relief. ^{1 2 3 4 5}

Is the treatment for vaginal dryness in breast cancer patients safe?

Research shows that both nonhormonal moisturizers like Replens and low-dose estrogen treatments have been found to be safe for treating vaginal dryness. Studies indicate that these treatments are well-tolerated, with low systemic absorption of estrogen, meaning they don't significantly affect the rest of the body. ^{1 2 5 6 7}

How does the treatment for vaginal dryness in breast cancer patients differ from other options?

The treatment using ESTRING and Replens is unique because it offers both hormonal and non-hormonal options for managing vaginal dryness. ESTRING provides localized estrogen therapy, which can be effective but may not be suitable for all breast cancer patients due to potential hormone sensitivity. Replens, on the other hand, is a non-hormonal moisturizer that can be a safe alternative for those who wish to avoid hormones, although its effects may be more temporary. ^{1 2 3 4 8}

Research Team

Polly Niravath, MD

Principal Investigator

Houston Methodist Cancer Center

Eligibility Criteria

This trial is for post-menopausal women aged 18 or older with stage I-III ER+ breast cancer, currently on adjuvant AI therapy, and suffering from vaginal dryness or related symptoms since starting the therapy. Participants must not use additional estrogen during the study and should have no current vaginal infections.

Inclusion Criteria

I have been diagnosed with early-stage, estrogen-receptor positive breast cancer.

I am post-menopausal based on age, surgery, or hormone levels.

I agree not to use any estrogen products for five years.

Exclusion Criteria

I have a current vaginal infection.

I have not used any estrogen products in the last 4 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either vaginal estrogen or Replens for the treatment of atrophic vaginitis

6 months

Visits at baseline, 4 weeks, 12 weeks, and 24 weeks

Follow-up

Participants are monitored for compliance with aromatase inhibitor therapy and changes in serum estrogen levels

4.5 years

Every 6 months

Long-term follow-up

Evaluation of breast cancer recurrence and vaginal dryness by vaginal pH

5 years

Treatment Details

Interventions

• ESTRING (Estrogen)
• Replens (Behavioural Intervention)

Trial Overview The REVIVE study compares two treatments for vaginal dryness in breast cancer patients on anti-estrogen treatment: a vaginal estrogen product called ESTRING and a non-hormonal moisturizer known as Replens.

Participant Groups

Group I: Estring Experimental Treatment 1 Intervention

ESTRING

Group II: REPLENS Active Control 1 Intervention

Replens

ESTRING is already approved in Canada for the following indications:

Approved in Canada as Estring for:

• Moderate to severe symptoms of vulvar and vaginal atrophy due to menopause

Who Is Running the Clinical Trial?

Polly A. Niravath, MD

Lead Sponsor

Trials

2

Recruited

80+

Findings from Research

In a clinical trial involving 45 breast cancer survivors, both the nonhormonal lubricant Replens and a placebo significantly reduced vaginal dryness and dyspareunia, with Replens showing a 60% improvement in dyspareunia scores (P = .05).

The beneficial effects of Replens were mostly observed within the first two weeks of treatment, indicating that it can provide quick relief for symptoms related to estrogen depletion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer. Loprinzi, CL., Abu-Ghazaleh, S., Sloan, JA., et al.[2022]

In a 12-week study involving 30 women, a nonhormonal bioadhesive vaginal moisturizer was found to be a safe and effective alternative to local estrogen therapy for treating vaginal dryness.

Both treatments significantly improved vaginal moisture, fluid volume, and elasticity, restoring the vaginal pH to premenopausal levels, indicating their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study: Replens versus local estrogen in menopausal women. Nachtigall, LE.[2022]

Up to 50% of postmenopausal women experience vulvovaginal atrophy-related symptoms, negatively affecting their quality of life, and many avoid standard topical vaginal estrogen due to safety concerns, especially breast cancer survivors.

Vaginal moisturizers may offer similar efficacy to topical vaginal estrogen and should be considered as a safe alternative for women seeking non-hormonal treatments, while lubricants provide temporary relief but lack long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-hormonal topical treatment of vulvovaginal atrophy: an up-to-date overview. Sinha, A., Ewies, AA.[2018]

Both low-dose vaginal estrogen treatments (estriol cream and estradiol tablets) significantly improved symptoms of urogenital atrophy in postmenopausal breast cancer survivors over 12 weeks, with effects measured by subjective and objective assessments.

The non-hormonal vaginal moisturizer provided only a temporary improvement in symptoms, highlighting that while both estrogen treatments are effective, the moisturizer's benefits do not last beyond the initial weeks of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study. Biglia, N., Peano, E., Sgandurra, P., et al.[2016]

The study involved 61 women with hormone receptor-positive early breast cancer, showing that the ultra-low dose 0.005% estriol vaginal gel significantly improved symptoms of vulvovaginal atrophy, including vaginal dryness and overall symptom scores after 12 weeks of treatment.

The treatment was safe, with minimal changes in hormone levels, indicating that it can be a suitable option for women with breast cancer experiencing vulvovaginal symptoms while on nonsteroidal aromatase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial. Hirschberg, AL., Sánchez-Rovira, P., Presa-Lorite, J., et al.[2022]

In a pilot study involving 28 female breast cancer patients, a 12-week treatment with a water-based cellulose gel significantly reduced the severity of vulvovaginal atrophy (VVA) symptoms, with the most bothersome symptom scores decreasing from an average of 2.71 to 1.33.

The gel was found to be safe, with 39% of participants reporting adverse events, and it is recommended as a suitable nonhormonal treatment option for VVA symptoms in breast cancer patients undergoing aromatase-inhibitor therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open, Uncontrolled Pilot Study on 12-Week Use of VagiVital for Treatment of Vulvovaginal Atrophy in Breast Cancer Patients Undergoing Adjuvant Aromatase-Inhibitor Therapy. Jonasson, AF., Åstrom, M.[2022]

TX-004HR, a low-dose vaginal estradiol softgel capsule, significantly improved symptoms of vulvar and vaginal atrophy in postmenopausal women, including vaginal dryness and dyspareunia, based on results from phase 2 and phase 3 studies.

The safety profile of TX-004HR was comparable to placebo, with negligible systemic absorption of estradiol, indicating it may be a safe treatment option that does not increase systemic estradiol levels above postmenopausal ranges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A vaginal estradiol softgel capsule, TX-004HR, has negligible to very low systemic absorption of estradiol: Efficacy and pharmacokinetic data review. Simon, JA., Archer, DF., Constantine, GD., et al.[2018]

Estriol (E3) can stimulate the growth of estrogen receptor-positive breast cancer cells, similar to estradiol (E2), at concentrations as low as 10(-10)M, indicating that it has a potent estrogenic effect.

The study suggests that breast cancer survivors should be cautious when using E3 for vulvovaginal atrophy, as it can activate genes associated with cell proliferation and growth in breast cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of estriol on growth, gene expression and estrogen response element activation in human breast cancer cell lines. Diller, M., Schüler, S., Buchholz, S., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Comparative study: Replens versus local estrogen in menopausal women. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Non-hormonal topical treatment of vulvovaginal atrophy: an up-to-date overview. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

An Open, Uncontrolled Pilot Study on 12-Week Use of VagiVital for Treatment of Vulvovaginal Atrophy in Breast Cancer Patients Undergoing Adjuvant Aromatase-Inhibitor Therapy. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

A vaginal estradiol softgel capsule, TX-004HR, has negligible to very low systemic absorption of estradiol: Efficacy and pharmacokinetic data review. [2018]

8. Ireland pubmed.ncbi.nlm.nih.gov

Effects of estriol on growth, gene expression and estrogen response element activation in human breast cancer cell lines. [2021]