Testing Low Dose Tamoxifen for Invasive Breast Cancer, the (LoTam) Trial
- Conditions
- Interventions
- Registration Number
- NCT06671912
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
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...
- 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:
...
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 1156
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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
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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
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Tumor size must be ≤ 3 cm by pathologic evaluation
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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
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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
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No pathological tumor size > 3 cm or pT4
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No definitive clinical or radiologic evidence of metastatic disease
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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
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No suspicious microcalcifications, densities, or palpable abnormalities in the ipsilateral or contralateral breast, unless biopsied and found to be benign
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An interval of no more than 20 weeks between the date of surgery and the date of registration
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Must have had a bilateral mammogram or MRI within 6 months prior to registration
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Must be intending to take endocrine therapy for at least 5 years duration
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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.)
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No use of oral hormone replacement therapy within 7 days prior to registration
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Age ≥ 18 years
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Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
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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
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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
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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
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No previous history of ipsilateral invasive breast cancer or ipsilateral ductal carcinoma in situ (DCIS), regardless of the disease-free interval
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No synchronous or previous contralateral invasive or non-invasive breast cancer
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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
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No patients with premenopausal status
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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
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HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (anastrozole, letrozole, exemestane, tamoxifen) Questionnaire Administration 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. Arm II (low dose tamoxifen) 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. Arm II (low dose tamoxifen) Mammogram 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. Arm I (anastrozole, letrozole, exemestane, tamoxifen) Anastrozole 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. Arm I (anastrozole, letrozole, exemestane, tamoxifen) Letrozole 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. Arm I (anastrozole, letrozole, exemestane, tamoxifen) Exemestane 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. Arm I (anastrozole, letrozole, exemestane, tamoxifen) 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. Arm I (anastrozole, letrozole, exemestane, tamoxifen) Mammogram 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. Arm I (anastrozole, letrozole, exemestane, tamoxifen) Magnetic Resonance Imaging 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. Arm I (anastrozole, letrozole, exemestane, tamoxifen) Dual X-ray Absorptiometry 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. Arm I (anastrozole, letrozole, exemestane, tamoxifen) Biospecimen Collection 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. Arm II (low dose tamoxifen) Magnetic Resonance Imaging 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. Arm II (low dose tamoxifen) Dual X-ray Absorptiometry 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. Arm II (low dose tamoxifen) Biospecimen Collection 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. Arm II (low dose tamoxifen) Questionnaire Administration 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.
- Primary Outcome Measures
Name Time Method Recurrence-free interval (RFI) From randomization to the first of the following breast cancer events: invasive ipsilateral breast or chest wall recurrence, regional recurrence, distant recurrence, and death from breast cancer up to 5 years The Kaplan-Meier method will be used to estimate the distribution of RFI times and a stratified log-rank test for non-inferiority will be used to assess whether RFI with low-dose tamoxifen is non-inferior to standard-of-care endocrine therapy in this patient population. Stratified Cox modeling will be used to estimate the hazard ratio and corresponding one-s...
- Secondary Outcome Measures
Name Time Method Endocrine therapy extent of nonadherence Up to 5 years The proportion of patients who stopped treatment early will be compared between the two treatment arms with a chi-square test. Additional analyses will be performed with respect to nonadherence. The proportion of patients who report any nonadherence will be compared between the two treatment arms using generalized estimating equations for logistic regression
Physician reported incidence of adverse events (AEs) Up to 10 years AEs will be evaluated and graded using the Common Terminology Criteria for Adverse Events version 5.0 with special focus on the incidence of fracture, osteoporosis, stroke and thromboembolic events.
Patient reported toxicities At baseline and up to 10 years Patient reported symptoms assessed using Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE). The proportion of patients with a maximum post-baseline score greater than 0 will be compared between arms using Fisher's exact test. The proportion of patients with a maximum post-baseline score greater than or equal to 3 will be co...
Invasive disease-free survival (iDFS) Up to 10 years IDFS will be defined as local, regional or distant recurrences, or contralateral invasive breast cancer, second non-breast primary cancer, and death from any cause. IDFS will be compared between the treatment arms with a stratified log rank test and a stratified Cox model will be used to generate the hazard ratio estimates (both a point estimate and a 95% CI...
Locoregional recurrence free-survival (LRFS) From randomization until invasive tumor recurs in the ipsilateral breast or chest wall, axillary, supraclavicular, or internal mammary nodes up to 10 years LRFS will be defined as the time from randomization until invasive tumor recurs in the ipsilateral breast or chest wall, axillary, supraclavicular, or internal mammary nodes (if before or synchronous with a systemic recurrence), whichever comes first. LRFS will be compared between the treatment arms with a stratified log rank test and a stratified Cox model ...
Distant disease-free survival (DDFS) From randomization until the tumor recurs distantly or death up to 10 years DDFS will be defined as the time from randomization until the tumor recurs distantly, or the patient dies, whichever comes first. DDFS will be compared between the treatment arms with a stratified log rank test and a stratified Cox model will be used to generate the hazard ratio estimates (both a point estimate and a 95% CI).
Overall survival (OS) From randomization until death up to 10 years OS will be defined as the time from randomization until death due to any cause. OS will be compared between the treatment arms with a stratified log rank test and a stratified Cox model will be used to generate the hazard ratio estimates (both a point estimate and a 95% CI).
Cumulative incidence rate of ductal carcinoma in situ (DCIS) From randomization until the occurrence of an ipsilateral or contralateral DCIS diagnosis up to 10 years Cumulative incidence rate of DCIS will be measured as the time from randomization until the occurrence of an ipsilateral or contralateral DCIS diagnosis. The cumulative incidence of DCIS will be analyzed with Kaplan-Meier estimates (curve starting at 0 rather than 1) and compared with a log rank test.