Acolbifene vs. Tamoxifen for Breast Cancer Prevention

Recruiting at 3 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticoagulants, Aspirin, Progestins, Immunosuppressives

Disqualifiers: Pregnancy, Breastfeeding, Diabetes, Liver disease, 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: 2

Duration: 6 months

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, acolbifene (acolbifene hydrochloride) and low-dose tamoxifen, to evaluate their effectiveness in preventing breast cancer in premenopausal women at high risk. Researchers aim to determine which treatment better reduces breast cancer risk, as indicated by mammogram images, breast tissue, and blood samples. Women with a higher likelihood of developing breast cancer due to factors like certain genetic mutations or family history of early-onset breast cancer may be suitable candidates. Participants will take one of the treatments for six months and undergo regular health check-ups. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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

The trial requires that you stop using aspirin and aspirin-containing products at least 3 weeks before certain procedures, and you must not use certain hormonal contraceptives or prescription anticoagulants. If you are on these medications, you may need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that acolbifene causes very few side effects in premenopausal women. It was linked to positive changes in breast cell growth and certain gene activities without major problems, suggesting that acolbifene is generally well-tolerated.

Tamoxifen, even at a low dose like in this study, is well-known and often used to reduce breast cancer risk. While it can have side effects, the low dose here should lower the chance of serious issues. Overall, both treatments have a history of being safe for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about acolbifene for breast cancer prevention because it offers a novel approach compared to the standard hormone therapies like tamoxifen. Acolbifene is a selective estrogen receptor modulator (SERM) that targets estrogen receptors differently, potentially offering similar preventive benefits with fewer side effects. This could be particularly beneficial for patients who are at high risk but have concerns about the side effects associated with current options. The possibility of reducing side effects while maintaining effectiveness is a significant step forward in preventive cancer care.

What evidence suggests that this trial's treatments could be effective for breast cancer prevention?

This trial will compare Acolbifene and Tamoxifen for breast cancer prevention. Research shows that Acolbifene, which participants in this trial may receive, might help lower breast cancer risk by influencing breast cell growth in response to estrogen. Earlier studies have found that Acolbifene leads to positive changes in breast cells and their genetic activity. Tamoxifen, another treatment option in this trial, has reduced breast cancer risk by 49% in women at higher risk, making it a common preventive choice. Both Acolbifene and Tamoxifen block estrogen, which can help stop cancer cells from growing. Although researchers continue to study Acolbifene, its mechanism appears promising for those at high risk of breast cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Carol J Fabian, MD

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

This trial is for premenopausal women aged 35 or older at high risk for breast cancer, with regular menstrual cycles or using certain contraceptives. Participants must have normal liver function tests, not be considering pregnancy for a year, and willing to use birth control. Exclusions include breastfeeding mothers, those with diabetes on medication, chronic liver disease history, prior invasive cancers within 5 years (except non-melanoma skin), current anticoagulant or hormonal treatments users.

Inclusion Criteria

I am 35 years old or older.

I am considered to be before menopause.

I agree to use birth control during and 8 weeks before and after the study due to risks from tamoxifen.

Exclusion Criteria

I am being treated for diabetes with prescription medication.

I am currently taking prescription drugs that suppress my immune system.

I am currently taking prescription blood thinners like Coumadin, Xarelto, or Eliquis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either acolbifene or tamoxifen orally once daily for 6 months. They also undergo 3D mammography and collection of blood samples during screening and at the end of treatment. RPFNA is performed during screening and on day 1-10 of their menstrual cycle.

6 months

Multiple visits (in-person) for mammography and RPFNA

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3-5 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Acolbifene Hydrochloride
• Tamoxifen

Trial Overview The study compares acolbifene against low dose tamoxifen in preventing breast cancer. It involves yearly mammograms plus MRI or ultrasound and may include preventive mastectomy consideration. The trial aims to measure the effects of both drugs on breast tissue markers and blood samples related to cancer risk.

How Is the Trial Designed?

Group I: Group 1 (acolbifene) Experimental Treatment 4 Interventions

Patients receive acolbifene PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo 3D mammography and collection of blood samples during screening and at the end of acolbifene treatment. In addition, patients undergo RPFNA during screening and during day 1-10 of their menstrual cycle, or if not menstruating, at the convenience of the patient and study staff.

Group II: Group 2 (tamoxifen) Active Control 5 Interventions

Patients receive tamoxifen PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo 3D mammography and collection of blood samples during screening and at the end of tamoxifen treatment. In addition, patients undergo RPFNA during screening and day 1-10 of their menstrual cycle, or if not menstruating, at the convenience of the patient and study staff.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Tamoxifen has been shown to reduce the incidence of breast cancer in women at increased risk, although some European studies did not confirm this benefit, and it is associated with an increased risk of endometrial cancer.

Raloxifene is a potential alternative for breast cancer prevention, but it has not yet been proven effective in reducing breast cancer incidence and should only be considered in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoprevention of breast cancer. Dalton, RR., Kallab, AM.[2017]

The P-1 trial demonstrated that tamoxifen is effective for breast cancer prevention in high-risk women, leading to its approval in 1998 as a safer alternative to more invasive procedures like mastectomy.

Raloxifene has been approved by the FDA for breast cancer prevention in postmenopausal women, showing a more favorable safety profile compared to tamoxifen, making it a viable option for women concerned about the side effects of tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized clinical trials of raloxifene: reducing the risk of osteoporosis and breast cancer in postmenopausal women. Olevsky, OM., Martino, S.[2015]

Tamoxifen has shown significant efficacy in reducing the risk of invasive breast cancer by 49% in one clinical trial, supporting its use for breast cancer prevention in women with a higher risk, as determined by the Gail model.

While tamoxifen is generally well tolerated, it carries risks such as increased chances of thromboembolic events and endometrial cancer; raloxifene also shows potential for breast cancer prevention but requires further research to understand its long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of antiestrogens for prevention of breast cancer. Reddy, P., Chow, MS.[2019]

After women with a higher risk of breast cancer read a decision aid about tamoxifen and raloxifene, only 1.8% discussed these medications with their doctor, indicating low interest in using them as preventive measures.

The majority of participants (54.7%) chose not to take either drug, with many not perceiving significant benefits or a change in their breast cancer risk from these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Women's interest in taking tamoxifen and raloxifene for breast cancer prevention: response to a tailored decision aid. Fagerlin, A., Dillard, AJ., Smith, DM., et al.[2022]

In a study of 22,235 older women, raloxifene use for breast cancer risk reduction was low overall, with only 1.8% to 4.0% usage depending on the estimated risk level, and it significantly decreased from 2010 to 2014.

Tamoxifen use was even lower, ranging from 0.36% to 0.85% across different risk categories, indicating that both medications are underutilized for breast cancer prevention in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of raloxifene and tamoxifen by breast cancer risk level in a Medicare-eligible cohort. Pinsky, PF., Miller, E., Heckman-Stoddard, B., et al.[2023]

Tamoxifen has been established as the gold standard for breast cancer prevention, demonstrating a significant 49% reduction in breast cancer incidence among women at increased risk.

Raloxifene shows even greater potential, with a suggested 74% reduction in breast cancer incidence from the MORE trial, leading to further investigation in the ongoing STAR study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast cancer chemoprevention: current clinical practice and future direction. Bevers, TB.[2019]

Tamoxifen has been shown to significantly reduce the risk of invasive breast cancer by 49% in high-risk women, according to the National Surgical Adjuvant Breast and Bowel Project P-1 trial, although some smaller European trials did not find a similar effect.

Due to potential side effects like endometrial cancer and thromboembolism, other agents such as raloxifene, which reduced breast cancer risk by 76% in a separate trial, are being investigated alongside tamoxifen for breast cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on breast cancer prevention. Rastogi, P., Vogel, VG.[2013]

Tamoxifen is being evaluated in ongoing clinical trials involving over 24,000 healthy women to determine its effectiveness in preventing breast cancer, with results expected by the year 2000.

While tamoxifen may provide significant benefits in breast cancer prevention, it is associated with adverse effects such as transient bone loss in premenopausal women and potential uterine complications in postmenopausal women, leading to investigations of alternative drugs like raloxifene and toremifene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Status of antiestrogen breast cancer prevention trials. Powles, TJ.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4670810/

Clinical Trial of Acolbifene in Premenopausal Women at ... In summary, acolbifene was associated with favorable changes in benign breast epithelial cell proliferation and estrogen inducible gene expression but minimal ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00853996

Acolbifene in Preventing Cancer in Premenopausal ... This phase II trial is studying how well acolbifene works in preventing cancer in premenopausal women at high risk of breast cancer.

3. withpower.com withpower.com/trial/phase-2-breast-neoplasms-11-2023-b29fd

Acolbifene vs. Tamoxifen for Breast Cancer Prevention Tamoxifen, a drug similar to Acolbifene, has been shown to reduce the risk of breast cancer by 49% in women at increased risk, making it a standard for breast ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05941520

Acolbifene Versus Low Dose Tamoxifen for the Prevention ... This phase IIA trial compares the effect of acolbifene versus low dose tamoxifen in preventing breast cancer in premenopausal women at high risk for ...

5. researchgate.net researchgate.net/publication/282127083_Clinical_Trial_of_Acolbifene_in_Premenopausal_Women_at_High_Risk_for_Breast_Cancer

Clinical Trial of Acolbifene in Premenopausal Women at ... The purpose of this study was to assess the feasibility of using the selective estrogen receptor modulator (SERM) acolbifene as a breast ...

6. prevention.cancer.gov prevention.cancer.gov/clinical-trials/clinical-trials-search/nct05941520

Acolbifene Versus Low Dose Tamoxifen for the Prevention of ... This study may help researchers measure the effects of acolbifene and low dose tamoxifen on markers of breast cancer risk in mammogram imaging, breast tissue, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26391916/

Clinical Trial of Acolbifene in Premenopausal Women at High ... In summary, acolbifene was associated with favorable changes in benign breast epithelial cell proliferation and estrogen-inducible gene expression but minimal ...