What is the mechanism of action of this treatment?

Estrogen receptor antagonists, like acolbifene, and selective estrogen receptor modulators (SERMs), like tamoxifen, are crucial in the treatment of breast cancer because they interfere with the cancer cells' ability to use estrogen, which is often necessary for their growth and proliferation. Acolbifene blocks estrogen receptors on breast cells, preventing estrogen from binding and stimulating cancer cell growth. Tamoxifen, a SERM, binds to estrogen receptors and either blocks or activates estrogen's effects depending on the tissue type. In breast tissue, tamoxifen acts as an antagonist, inhibiting cancer cell growth. These mechanisms are vital for patients as they help reduce the risk of cancer progression and recurrence by targeting the hormonal pathways that many breast cancers depend on.

What side effects are associated with this type of intervention?

Common side effects of breast cancer treatments similar to acolbifene and low dose tamoxifen, which are estrogen receptor antagonists and selective estrogen receptor modulators (SERMs), include hot flashes, vaginal dryness or discharge, and an increased risk of blood clots. Tamoxifen specifically has been associated with a risk of endometrial cancer and cataracts. Both treatments may also cause mild alopecia (hair thinning) and other menopausal symptoms.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of breast cancer that modulate estrogen receptors. Tamoxifen, a selective estrogen receptor modulator (SERM), was one of the first and remains a cornerstone in the treatment of estrogen receptor-positive breast cancer. It works by blocking estrogen receptors on breast cancer cells, thereby inhibiting their growth. Another class of drugs, aromatase inhibitors (e.g., anastrozole, letrozole), reduces estrogen levels in postmenopausal women by inhibiting the enzyme aromatase, which converts androgens to estrogen. Fulvestrant, an estrogen receptor antagonist, is also FDA-approved and works by degrading the estrogen receptor. These treatments are crucial for managing hormone receptor-positive breast cancer and are similar in function to the drugs being studied in the trial involving acolbifene and low dose tamoxifen.

What other types of research exist?

Promising novel alternatives for breast cancer treatment in 2024 include: 1) CDK4/6 inhibitors (e.g., Palbociclib, Ribociclib) which target cell cycle regulation, 2) PARP inhibitors (e.g., Olaparib, Talazoparib) for patients with BRCA mutations, 3) Immune checkpoint inhibitors (e.g., Pembrolizumab) for triple-negative breast cancer, and 4) PI3K inhibitors (e.g., Alpelisib) for patients with PIK3CA mutations. These therapies offer targeted approaches and have shown significant efficacy in recent clinical trials.

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Selective Estrogen Receptor Modulator

Acolbifene vs. Tamoxifen for Breast Cancer Prevention

Phase 2

Recruiting

Led By Carol J Fabian

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age >= 35 years

Eastern Cooperative Oncology Group (ECOG) current performance status ≤2 as documented within 3 months prior to randomization (Karnofsky score >= 60%)

Must not have

Type I or Type II diabetes mellitus requiring treatment with prescription medication

Current use of prescription immunosuppressive drugs

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to 6 months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects of acolbifene and tamoxifen can include hot flashes, vaginal dryness or discharge, mood swings, changes in menstruation patterns, leg cramps, headache and an increased risk of blood clots.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 35 years old or older.

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My current health allows me to do daily activities with little or no help.

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I am on long-term antiviral treatment for herpes simplex virus.

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My hepatitis B virus load is undetectable with treatment.

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I had hepatitis C but am cured, or if currently treated, my viral load is undetectable.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am being treated for diabetes with prescription medication.

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

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

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I haven't used progesterone/progestin birth control in the last 8 weeks.

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I am allergic to tamoxifen, acolbifene, or similar drugs.

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I can stop taking aspirin or aspirin products three weeks before each test.

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I have a history of chronic liver disease, such as NASH or hepatitis C.

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I have been treated with tamoxifen for over 2 months.

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I have been treated with acolbifene for over 2 months.

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I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

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I am not currently breastfeeding nor have I breastfed in the last 12 months.

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I have implants in both breasts.

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I haven't had a cancer more serious than T1 stage, except for non-melanoma skin cancer, in the last 5 years.

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I am currently pregnant.

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I had breast cancer within the last 5 years.

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I have had a deep vein thrombosis, pulmonary embolus, or stroke before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline up to 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline up to 6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline up to 6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in the relative abundance of the specific sequence of messenger ribonucleic acid (mRNA) that codes for AGR2

Secondary study objectives

Change in Estrogen Response Gene Index (ERGI)

Change in Hot Flash Score

Change in Menopause-Specific Quality of Life (MENQOL)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Group 1 (acolbifene)Experimental Treatment3 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 Control4 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2020

0 / 21Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Estrogen receptor antagonists, like acolbifene, and selective estrogen receptor modulators (SERMs), like tamoxifen, are crucial in the treatment of breast cancer because they interfere with the cancer cells' ability to use estrogen, which is often necessary for their growth and proliferation. Acolbifene blocks estrogen receptors on breast cells, preventing estrogen from binding and stimulating cancer cell growth. Tamoxifen, a SERM, binds to estrogen receptors and either blocks or activates estrogen's effects depending on the tissue type. In breast tissue, tamoxifen acts as an antagonist, inhibiting cancer cell growth. These mechanisms are vital for patients as they help reduce the risk of cancer progression and recurrence by targeting the hormonal pathways that many breast cancers depend on.