Testing Low Dose Tamoxifen for Invasive Breast Cancer, the (LoTam) Trial
Purpose
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.
Conditions
- Anatomic Stage 0 Breast Cancer AJCC v8
- Anatomic Stage 1 Breast Cancer AJCC v8
- Anatomic Stage IIA Breast Cancer AJCC v8
- Estrogen Receptor-Positive Breast Carcinoma
- HER2-Negative Breast Carcinoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- Unilateral invasive adenocarcinoma of the breast that is histologically confirmed
- Invasive breast cancer is estrogen receptor positive in ≥ 10% of cells
- HER2 negative by current American Society of Clinical Oncology (ASCO)/College
of American Pathologists (CAP) guidelines
- The patient must have a multigene assay with a low-risk score, including any of the
following (if more than one genomic assay was obtained, both are required to be
low-risk):
- Oncotype DX recurrence score ≤ 25
- Mamma Print low risk
- Prosigna risk of recurrence ≤ 40
- Tumor size must be ≤ 3 cm by pathologic evaluation
- Adequate surgical removal of all clinically evident disease in the breast with
either breast conserving surgery or mastectomy. Negative margins on final pathology
are required. Additional excisions may be performed to obtain clear margins before
registration
- No clinical (cN1, cN2, cN3) or pathologic (pN1mi, pN1, pN2, or pN3) evidence of
lymph node involvement on either needle biopsy or surgical lymph node assessment.
Patients with pN0(i+) or pN0 (mol+) are eligible
- Surgical axillary staging (sentinel lymph node biopsy ± axillary lymph node
dissection) is completed according to physician discretion
- For patients with negative preoperative axillary ultrasonography, clinicians
may selectively choose to forego surgical axillary staging. Ipsilateral
axillary ultrasound showing no lymph node involvement with no evidence of
lymphadenopathy or suspicious thickening is required in this scenario
- No pathological tumor size > 3 cm or pT4
- No definitive clinical or radiologic evidence of metastatic disease
- No palpable or radiographically suspicious axillary, supraclavicular,
infraclavicular, or internal mammary lymph nodes, unless there is histologic
confirmation that these lymph nodes are negative for tumor
- No suspicious microcalcifications, densities, or palpable abnormalities in the
ipsilateral or contralateral breast, unless biopsied and found to be benign
- An interval of no more than 20 weeks between the date of surgery and the date of
registration
- Must have had a bilateral mammogram or MRI within 6 months prior to registration
- Must be intending to take endocrine therapy for at least 5 years duration
- No prior treatment with endocrine therapy or chemotherapy for the currently
diagnosed breast cancer prior to registration. (Short course endocrine therapy of ≤
6 weeks duration is acceptable after core biopsy and before surgery, if genomic
testing is assessed on the biopsy core and meets eligibility requirements for a
low-risk score.)
- No use of oral hormone replacement therapy within 7 days prior to registration
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Postmenopausal status confirmed as:
- No spontaneous menses ≥ 1 year
- No menses for < 1 year with follicle stimulating hormone (FSH) and estradiol
levels within a postmenopausal range according to institutional standards
- Previous bilateral surgical oophorectomy
- None of the following conditions:
- Abnormal or dysfunctional uterine bleeding within 1 year prior to study
enrollment
- Any patient with known atypia or endometrial pathology that the opinion of the
treating investigator would place the patient at undue risk of endometrial
cancer with tamoxifen.
- Any patient with a known hypercoagulable state that in the opinion of the
treating investigator would put the patient at undue risk of venous
thromboembolism with tamoxifen
- No history of breast or thoracic radiotherapy for any previous condition. Patients
may complete radiotherapy for the currently diagnosed breast cancer prior to
registering for the study. In this scenario, registration must be completed within
12 weeks of completing breast radiotherapy
- No previous history of ipsilateral invasive breast cancer or ipsilateral ductal
carcinoma in situ (DCIS), regardless of the disease-free interval
- No synchronous or previous contralateral invasive or non-invasive breast cancer
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial
- No patients with premenopausal status
- No current treatment with any endocrine therapy for breast cancer prevention or
osteoporosis, including raloxifene, tamoxifen, or other selective estrogen receptor
modulator. Patients intending to continue oral hormone replacement are not eligible
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months are eligible for this trial
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Arm I (anastrozole, letrozole, exemestane, tamoxifen) |
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. |
|
|
Experimental Arm II (low dose tamoxifen) |
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. |
|
Recruiting Locations
Galveston, Texas 77555-0565
More Details
- Status
- Recruiting
- Sponsor
- Alliance for Clinical Trials in Oncology
Detailed Description
The primary and secondary objectives of the study: PRIMARY OBJECTIVE: I. To evaluate whether the recurrence-free interval (RFI) with low-dose tamoxifen is non-inferior to standard-of-care endocrine therapy among post-menopausal women with early-stage, low molecular risk breast cancer. SECONDARY OBJECTIVES: I. To compare endocrine therapy nonadherence rates between treatment arms. II. To compare the incidence of adverse events between treatment arms, including osteoporosis, fracture, endometrial carcinoma, stroke, and deep vein thrombosis. III. To compare endocrine therapy-related patient reported symptoms between treatment arms. IV. To compare the invasive disease-free survival between treatment arms. V. To compare the locoregional breast cancer recurrence between treatment arms. VI. To compare distant recurrence free survival between treatment arms. VII. To compare overall survival between treatment arms. VIII. To compare ductal carcinoma in situ (DCIS) incidence (ipsilateral and contralateral) between treatment arms. IX. To evaluate the association between radiotherapy modality (no radiation, partial breast radiation, and whole breast radiation) and RFI in each arm. X. To explore important measures of quality of life that would reasonably be expected to vary by study arm, including global quality of life and reasons for nonadherence. XI. To compare change in mammographic density at two years between treatment arms. XII. To conduct a within patient comparison of automated versus (vs) semi-automated mammographic density determination. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive standard of care endocrine therapy per physician choice with either anastrozole orally (PO), letrozole PO, exemestane PO or standard dose tamoxifen PO once daily (QD) for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients may also undergo mammogram or magnetic resonance imaging (MRI), dual X-ray absorptiometry (DEXA), and blood sample collection on study. ARM II: Patients receive low-dose tamoxifen PO every other day (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. After completion of study treatment, patients are followed up for 10 years after registration.