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

Trial Summary

What is the purpose of this trial?

This trial is testing two pills, acolbifene and low dose tamoxifen, to prevent breast cancer in premenopausal women at high risk. These women are chosen because they have a much higher chance of developing breast cancer. The drugs work by blocking estrogen, which can help stop the growth of cancer cells. Acolbifene is being assessed for breast cancer prevention, while tamoxifen has been widely studied and used for reducing breast cancer risk.

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.

What data supports the effectiveness of the drug Acolbifene Hydrochloride 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 cancer prevention. Raloxifene, another similar drug, showed a 74% reduction in breast cancer incidence in a trial, suggesting that drugs in this category can be effective for prevention. ^{1 2 3 4 5}

Is Acolbifene or Tamoxifen safe for breast cancer prevention?

Tamoxifen is generally well tolerated but may increase the risk of blood clots and endometrial cancer (cancer of the lining of the uterus), and it has been linked to eye problems. Raloxifene, another similar drug, has a more favorable safety profile than Tamoxifen, but more research is needed to fully understand its long-term safety. ^{1 3 5 6 7}

How does Acolbifene differ from Tamoxifen for breast cancer prevention?

Acolbifene is being compared to Tamoxifen, which is a well-known drug for reducing breast cancer risk but has side effects like an increased risk of endometrial cancer. Acolbifene may offer a different side effect profile or effectiveness, making it a potentially novel option for breast cancer prevention. ^{1 2 5 7 8}

Research Team

Carol J Fabian, MD

Principal Investigator

University of Kansas Medical Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

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

Chemoprevention of breast cancer. [2017]

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

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

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

Status of antiestrogen breast cancer prevention trials. [2016]

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

Update on breast cancer prevention. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of antiestrogens for prevention of breast cancer. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Women's interest in taking tamoxifen and raloxifene for breast cancer prevention: response to a tailored decision aid. [2022]

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

Use of raloxifene and tamoxifen by breast cancer risk level in a Medicare-eligible cohort. [2023]