Provera for Endometrial Cancer Risk Reduction

(RESToRE Trial)

Overseen By Rachel Woima, BSc

Age: Any Age

Sex: Female

Trial Phase: Phase 4

Sponsor: University of British Columbia

Must be taking: Medroxyprogesterone acetate

Must not be taking: Hormone therapy, Male hormones, Tamoxifen, Aromatase inhibitors

Disqualifiers: Abnormal uterine bleeding, IUD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to lower the risk of endometrial cancer, focusing on individuals at higher risk. Participants will take Provera (a hormone therapy) for 10 days to determine if it causes withdrawal bleeding, which helps identify those who might benefit from further care, such as hormone therapy or biopsy. Researchers are also exploring easy, self-collection methods to study DNA changes and the body's bacteria, potentially allowing some to avoid a biopsy in the future. The study seeks postmenopausal women with a BMI over 34.9 or a 2% or greater risk of developing endometrial cancer. Participants should not be on hormone therapies or have experienced abnormal uterine bleeding. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Do I need to stop my current medications to join the trial?

The trial requires that you are not taking hormone therapy for menopause, male hormones, anti-endocrine therapy, or aromatase inhibitors. If you are on any of these medications, you would need to stop them to participate.

What is the safety track record for Provera?

Research has shown that Provera (medroxyprogesterone acetate), tested in this trial, has been used for other health conditions and is generally considered safe. Studies have found that Provera can lower the risk of endometrial hyperplasia, a condition that can lead to endometrial cancer. Some people have reported side effects like weight gain, liver problems, and changes in blood tests related to blood clotting. It is important to know that taking Provera might increase the risk of heart problems, strokes, or certain types of cancer, such as breast or uterine cancer.

In this trial, Provera is administered for a short period of 10 days. The FDA has already approved the treatment for other uses, indicating it is well-understood. However, individual reactions may vary, so it is important to consider these possible risks when deciding to join a trial. Always consult a healthcare provider about any concerns. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Provera is unique because it uses medroxyprogesterone acetate, a synthetic form of the hormone progesterone, to potentially reduce the risk of endometrial cancer. Unlike many current treatments that often focus on surgery or chemotherapy, Provera offers a non-invasive approach by targeting the hormonal pathways involved in cancer development. Researchers are excited about this treatment because it could provide a preventive option, potentially reducing the need for more aggressive treatments later on.

What evidence suggests that Provera might be an effective treatment for reducing endometrial cancer risk?

Research has shown that medroxyprogesterone acetate, also known as Provera, can help treat certain types of endometrial cancer. In patients with early-stage endometrial cancer, Provera has demonstrated potential benefits, allowing some to avoid more aggressive treatments. Studies have found that about 30% of patients respond to this hormone therapy, with even better results in specific situations. Specifically, for patients with endometrial cancer that has positive progesterone receptors, the response rate was 55%. This trial will evaluate the effectiveness of a 10-day course of Provera in reducing the risk of endometrial cancer in high-risk individuals, based on this promising evidence. ^{1 2 3 6 7}

Who Is on the Research Team?

Aline Talhouk, PhD

Principal Investigator

University of British Columbia, Department of Obstetrics and Gynecology

Jessica McAlpine, MD

Principal Investigator

University of British Columbia, Department of Obstetrics and Gynecology

Are You a Good Fit for This Trial?

This trial is for postmenopausal individuals at least three years past their last menstrual period, who still have an intact uterus. It's not open to those on hormone therapy for menopause, taking male hormones or anti-endocrine drugs like tamoxifen, using aromatase inhibitors, experiencing abnormal uterine bleeding, or with an IUD.

Inclusion Criteria

I have not had a menstrual period for at least three years.

I have not had a hysterectomy.

Exclusion Criteria

I am currently taking hormone therapy for cancer.

I am currently on hormone therapy for menopause.

I am currently taking male hormones.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (virtual)

Progesterone Challenge Test

Participants undergo a 10-day course of medroxyprogesterone acetate to identify endometrial proliferation

2 weeks

1 visit (in-person or virtual)

At-home Vaginal Sampling

Participants collect vaginal samples at home for DNA and microbiome analysis

1 week

No visits required

Lifestyle Intervention

Participants engage in a personalized diet and exercise program over four weeks

4 weeks

6 virtual sessions

Follow-up

Participants are monitored for adherence and progress in the lifestyle intervention

3 months

1 check-in (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Provera

Trial Overview The study tests the feasibility of a screening method and risk-reducing treatments in people at high risk for endometrial cancer. Participants will take Provera (medroxyprogesterone acetate) for ten days; if they bleed afterwards, it indicates potential endometrial proliferation and leads to standard care including possible biopsy and hormone therapy.

How Is the Trial Designed?

Group I: Progesterone Challenge Test Experimental Treatment 1 Intervention

10-day course of medroxyprogesterone acetate (Provera) 10 mg per os (po) daily.

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Canadian Cancer Society (CCS)

Collaborator

Trials

84

Recruited

42,100+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10450383/

Efficacy and prognosis of adjuvant treatment of endometrial ... Adjuvant treatment with medroxyprogesterone acetate may have potential long-term prognostic benefits for patients with early-stage high-risk endometrial cancer.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S074879832401638X

Oncologic and pregnancy outcomes of fertility-sparing ... The study evaluates the effectiveness of medroxyprogesterone acetate therapy in patients with early-stage endometrial cancer, atypical endometrial hyperplasia ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10100186/

The effect of progestin therapy in advanced and recurrent ... The ORR of progestin therapy was 30% (95% CI 25–36), the clinical benefit rate was 52% (95% CI 42–61). In PR‐positive EC, the ORR was 55%, compared with 12% in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05651282

NCT05651282 | Risk Evaluation and Screening to Tailor ... This study proposes to assess feasibility and acceptability of screening and risk reducing interventions in individuals at increased for endometrial cancer ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/011839s083lbl.pdf

PROVERA® (medroxyprogesterone acetate tablets, USP ... In a 3-year, double-blind, placebo-controlled study of 356 nonhysterectomized, postmenopausal women between 45 and 64 years of age randomized to receive placebo.

6. mayoclinic.org mayoclinic.org/drugs-supplements/medroxyprogesterone-oral-route/description/drg-20146771

Medroxyprogesterone (oral route) - Side effects & dosage Using this medicine may increase your risk of heart attack, stroke, blood clots, dementia, breast cancer, or uterine cancer. Talk with your ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24021911

Oral Progestin Treatment for Early-Stage Endometrial Cancer The main recorded adverse effects included body weight gain (79.2%), liver dysfunction (13.2%), and abnormal blood coagulation test results (1.9%). Similar ...