Low Dose Tamoxifen for Breast Cancer

(LoTam Trial)

Recruiting at 112 trial locations

Overseen By Jack Beranek

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: Endocrine therapy

Must not be taking: Hormone replacement

Disqualifiers: Premenopausal, Endometrial pathology, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years

1156 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effect of low dose tamoxifen to usual hormonal therapy, including aromatase inhibitors, in treating post-menopausal women with hormone positive, HER2 negative early stage breast cancer. Tamoxifen is in a class of medications known as antiestrogens. It blocks the activity of estrogen (a female hormone) in the breast. This may stop the growth of some breast tumors that need estrogen to grow. Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, prevent the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibitors are used as a type of hormone therapy to treat postmenopausal women with hormone-dependent breast cancer. Giving low dose tamoxifen may be more effective compared to usual hormone therapy in treating post-menopausal women with hormone-positive, HER2 negative early stage breast cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any endocrine therapy for breast cancer prevention or osteoporosis, including tamoxifen or hormone replacement therapy, when you start the trial.

What data supports the effectiveness of the drug Tamoxifen for breast cancer?

Research shows that low-dose Tamoxifen can reduce the recurrence of breast cancer after surgery and lower the risk of developing breast cancer in women at risk by about 50%, without increasing side effects. ^{1 2 3 4 5}

Is low-dose tamoxifen safe for humans?

Low-dose tamoxifen is generally considered safe for humans, with fewer side effects than the standard 20 mg dose. While it can increase the risk of endometrial cancer and blood clots, these risks are lower at reduced doses. ^{3 4 6 7 8}

How is low-dose tamoxifen different from other breast cancer drugs?

Low-dose tamoxifen is unique because it uses a smaller dose (5 mg/day) compared to the standard 20 mg/day, which helps reduce side effects like endometrial cancer and blood clots while still effectively preventing breast cancer recurrence. ^{1 2 6 7 9}

Eligibility Criteria

This trial is for post-menopausal women with hormone-positive, HER2 negative early stage breast cancer. Participants must have a specific type of invasive breast cancer that's estrogen receptor positive and not spread to lymph nodes. Tumors should be small (≤3cm) and surgically removed with clear margins. Women who've had certain high-risk scores on cancer recurrence tests or evidence of lymph node involvement can't join.

Inclusion Criteria

My breast cancer is classified as low risk by the MammaPrint test.

My breast cancer recurrence risk score is 40 or less.

My breast cancer is estrogen receptor positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either low-dose tamoxifen or standard-of-care endocrine therapy for up to 5 years

5 years

Regular visits for mammogram or MRI, DEXA, and blood sample collection

Follow-up

Participants are monitored for recurrence-free interval, adverse events, and overall survival

10 years

Treatment Details

Interventions

• Tamoxifen

Trial Overview The LoTam Trial is testing the effectiveness of low dose tamoxifen against usual hormonal therapies like anastrozole, letrozole, and exemestane in treating early stage breast cancer. The study aims to see if tamoxifen, which blocks estrogen in the breast, could be more effective than aromatase inhibitors that prevent formation of estradiol.

Participant Groups

Group I: Arm II (low dose tamoxifen) Experimental Treatment 6 Interventions

Patients receive low-dose tamoxifen PO QOD for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients may also undergo mammogram or MRI, DEXA, and blood sample collection on study.

Group II: Arm I (anastrozole, letrozole, exemestane, tamoxifen) Active Control 9 Interventions

Patients receive standard of care endocrine therapy per physician choice with either anastrozole PO, letrozole PO, exemestane PO or standard dose tamoxifen PO QD for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients may also undergo mammogram or MRI, DEXA, and blood sample collection on study.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 282 prostate cancer patients, tamoxifen at a dose of 20 mg daily significantly reduced the incidence of breast events caused by bicalutamide treatment, with only 8.8% of patients experiencing these events compared to 96.7% in the placebo group at 6 months.

The use of tamoxifen did not negatively impact prostate-specific antigen (PSA) suppression, indicating that it effectively manages breast side effects without compromising cancer control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen as prophylaxis for prevention of gynaecomastia and breast pain associated with bicalutamide 150 mg monotherapy in patients with prostate cancer: a randomised, placebo-controlled, dose-response study. Fradet, Y., Egerdie, B., Andersen, M., et al.[2014]

Tamoxifen is widely used by 7 million women for breast cancer treatment and has been shown to significantly improve patient survival with minimal adverse effects.

While there is a slightly increased risk of endometrial cancer at the 20 mg/d dosage, this risk is considered minimal, and routine monitoring primarily involves clinical examinations rather than systematic endometrial testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Monitoring women on tamoxifen ]. Lansac, J., Diouf, A.[2013]

References

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

Effect Modifiers of Low-Dose Tamoxifen in a Randomized Trial in Breast Noninvasive Disease. [2022]

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

Biologic activity of tamoxifen at low doses in healthy women. [2019]

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

A Randomized Phase IIb Study of Low-dose Tamoxifen in Chest-irradiated Cancer Survivors at Risk for Breast Cancer. [2022]

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

Effect of blood tamoxifen concentrations on surrogate biomarkers in a trial of dose reduction in healthy women. [2017]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Tamoxifen as prophylaxis for prevention of gynaecomastia and breast pain associated with bicalutamide 150 mg monotherapy in patients with prostate cancer: a randomised, placebo-controlled, dose-response study. [2014]

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

A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers. [2022]

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

Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia. [2020]

8. France pubmed.ncbi.nlm.nih.gov

[Monitoring women on tamoxifen ]. [2013]

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

Benefit of low-dose tamoxifen in a large observational cohort of high risk ER positive breast DCIS. [2017]