Clinical trial NCT06671912: Testing Low Dose Tamoxifen for Invasive Breast Cancer, the (LoTam) Trial
Official title: LoTam: A Randomized, Phase III Clinical Trial of Low-Dose Tamoxifen for Selected Patients With Molecular Low-Risk Early-Stage Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
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
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2024-11-04
Enrollment: 1156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

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.

Eligibility 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

Primary outcomes:
measure: Recurrence-free interval (RFI)
timeFrame: 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
Secondary outcomes:
measure: Endocrine therapy extent of nonadherence
timeFrame: Up to 5 years
measure: Physician reported incidence of adverse events (AEs)
timeFrame: Up to 10 years
measure: Patient reported toxicities
timeFrame: At baseline and up to 10 years
measure: Invasive disease-free survival (iDFS)
timeFrame: Up to 10 years
measure: Locoregional recurrence free-survival (LRFS)
timeFrame: From randomization until invasive tumor recurs in the ipsilateral breast or chest wall, axillary, supraclavicular, or internal mammary nodes up to 10 years
measure: Distant disease-free survival (DDFS)
timeFrame: From randomization until the tumor recurs distantly or death up to 10 years
measure: Overall survival (OS)
timeFrame: From randomization until death up to 10 years
measure: Cumulative incidence rate of ductal carcinoma in situ (DCIS)
timeFrame: From randomization until the occurrence of an ipsilateral or contralateral DCIS diagnosis up to 10 years
Other outcomes:
Locations:
city: Buena Park
country: United States
facility: Keck Medicine of USC Buena Park
state: California
city: Chico
country: United States
facility: Enloe Medical Center
state: California
city: Dublin
country: United States
facility: Kaiser Permanente Dublin
state: California
city: Fremont
country: United States
facility: Kaiser Permanente-Fremont
state: California
city: Fresno
country: United States
facility: Kaiser Permanente-Fresno
state: California
city: Los Angeles
country: United States
facility: Los Angeles General Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Modesto
country: United States
facility: Kaiser Permanente-Modesto
state: California
city: Newport Beach
country: United States
facility: USC Norris Oncology/Hematology-Newport Beach
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: Roseville
country: United States
facility: Kaiser Permanente-Roseville
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Downtown Commons
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente-South Sacramento
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente-San Francisco
state: California
city: San Jose
country: United States
facility: Kaiser Permanente-Santa Teresa-San Jose
state: California
city: San Leandro
country: United States
facility: Kaiser Permanente San Leandro
state: California
city: San Rafael
country: United States
facility: Kaiser San Rafael-Gallinas
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Medical Center - Santa Clara
state: California
city: Santa Rosa
country: United States
facility: Kaiser Permanente-Santa Rosa
state: California
city: South San Francisco
country: United States
facility: Kaiser Permanente-South San Francisco
state: California
city: Truckee
country: United States
facility: Gene Upshaw Memorial Tahoe Forest Cancer Center
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente-Vallejo
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente-Walnut Creek
state: California
city: Stamford
country: United States
facility: Stamford Hospital/Bennett Cancer Center
state: Connecticut
city: Millville
country: United States
facility: Beebe South Coastal Health Campus
state: Delaware
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants PA
state: Delaware
city: Rehoboth Beach
country: United States
facility: Beebe Health Campus
state: Delaware
city: Washington
country: United States
facility: Kaiser Permanente-Capitol Hill Medical Center
state: District of Columbia
city: Honolulu
country: United States
facility: Kaiser Permanente Moanalua Medical Center
state: Hawaii
city: Coeur d'Alene
country: United States
facility: Kootenai Health - Coeur d'Alene
state: Idaho
city: Post Falls
country: United States
facility: Kootenai Clinic Cancer Services - Post Falls
state: Idaho
city: Sandpoint
country: United States
facility: Kootenai Clinic Cancer Services - Sandpoint
state: Idaho
city: Bloomington
country: United States
facility: Illinois CancerCare-Bloomington
state: Illinois
city: Canton
country: United States
facility: Illinois CancerCare-Canton
state: Illinois
city: Carthage
country: United States
facility: Illinois CancerCare-Carthage
state: Illinois
city: Danville
country: United States
facility: Carle at The Riverfront
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Illinois - Decatur
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Dixon
country: United States
facility: Illinois CancerCare-Dixon
state: Illinois
city: Effingham
country: United States
facility: Carle Physician Group-Effingham
state: Illinois
city: Effingham
country: United States
facility: Crossroads Cancer Center
state: Illinois
city: Eureka
country: United States
facility: Illinois CancerCare-Eureka
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare-Galesburg
state: Illinois
city: Kewanee
country: United States
facility: Illinois CancerCare-Kewanee Clinic
state: Illinois
city: Macomb
country: United States
facility: Illinois CancerCare-Macomb
state: Illinois
city: Mattoon
country: United States
facility: Carle Physician Group-Mattoon/Charleston
state: Illinois
city: Ottawa
country: United States
facility: Illinois CancerCare-Ottawa Clinic
state: Illinois
city: Pekin
country: United States
facility: Illinois CancerCare-Pekin
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peru
country: United States
facility: Illinois CancerCare-Peru
state: Illinois
city: Princeton
country: United States
facility: Illinois CancerCare-Princeton
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Springfield
country: United States
facility: Springfield Memorial Hospital
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Washington
country: United States
facility: Illinois CancerCare - Washington
state: Illinois
city: Ames
country: United States
facility: Mary Greeley Medical Center
state: Iowa
city: Ames
country: United States
facility: McFarland Clinic - Ames
state: Iowa
city: Boone
country: United States
facility: McFarland Clinic - Boone
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Oncology Associates at Mercy Medical Center
state: Iowa
city: Fort Dodge
country: United States
facility: McFarland Clinic - Trinity Cancer Center
state: Iowa
city: Jefferson
country: United States
facility: McFarland Clinic - Jefferson
state: Iowa
city: Marshalltown
country: United States
facility: McFarland Clinic - Marshalltown
state: Iowa
city: New Orleans
country: United States
facility: Ochsner Medical Center Jefferson
state: Louisiana
city: Baltimore
country: United States
facility: Kaiser Permanente-Woodlawn Medical Center
state: Maryland
city: Gaithersburg
country: United States
facility: Kaiser Permanente-Gaithersburg Medical Center
state: Maryland
city: Largo
country: United States
facility: Kaiser Permanente - Largo Medical Center
state: Maryland
city: Lutherville
country: United States
facility: Kaiser Permanente Lutherville - Timonium Medical Center
state: Maryland
city: Escanaba
country: United States
facility: OSF Saint Francis Hospital and Medical Group
state: Michigan
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Farmington
country: United States
facility: Parkland Health Center - Farmington
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Sainte Genevieve
country: United States
facility: Sainte Genevieve County Memorial Hospital
state: Missouri
city: Sullivan
country: United States
facility: Missouri Baptist Sullivan Hospital
state: Missouri
city: Sunset Hills
country: United States
facility: BJC Outpatient Center at Sunset Hills
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Health Deaconess Hospital
state: Montana
city: Great Falls
country: United States
facility: Benefis Sletten Cancer Institute
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: East Syracuse
country: United States
facility: Hematology Oncology Associates of Central New York-East Syracuse
state: New York
city: Cincinnati
country: United States
facility: Good Samaritan Hospital - Cincinnati
state: Ohio
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Conroe
country: United States
facility: MD Anderson in The Woodlands
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson West Houston
state: Texas
city: League City
country: United States
facility: MD Anderson League City
state: Texas
city: Sugar Land
country: United States
facility: MD Anderson in Sugar Land
state: Texas
city: McLean
country: United States
facility: Kaiser Permanente Tysons Corner Medical Center
state: Virginia
city: Mechanicsville
country: United States
facility: Bon Secours Memorial Regional Medical Center
state: Virginia
city: Midlothian
country: United States
facility: Bon Secours Saint Francis Medical Center
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Saint Mary's Hospital
state: Virginia
city: Woodbridge
country: United States
facility: Kaiser Permanente-Caton Hill Medical Center
state: Virginia
city: Antigo
country: United States
facility: Langlade Hospital and Cancer Center
state: Wisconsin
city: Appleton
country: United States
facility: ThedaCare Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital Cancer Center Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital Cancer Center at Saint Mary's
state: Wisconsin
city: Medford
country: United States
facility: Aspirus Medford Hospital
state: Wisconsin
city: Oconto Falls
country: United States
facility: Saint Vincent Hospital Cancer Center at Oconto Falls
state: Wisconsin
city: Rhinelander
country: United States
facility: Aspirus Cancer Care - James Beck Cancer Center
state: Wisconsin
city: Sheboygan
country: United States
facility: Saint Vincent Hospital Cancer Center at Sheboygan
state: Wisconsin
city: Sheboygan
country: United States
facility: Sheboygan Phyisicans Group
state: Wisconsin
city: Stevens Point
country: United States
facility: Aspirus Cancer Care - Stevens Point
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Saint Vincent Hospital Cancer Center at Sturgeon Bay
state: Wisconsin
city: Wausau
country: United States
facility: Aspirus Regional Cancer Center
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Aspirus Cancer Care - Wisconsin Rapids
state: Wisconsin
city: Manati
country: Puerto Rico
facility: Doctors Cancer Center
city: San Juan
country: Puerto Rico
facility: Centro Comprensivo de Cancer de UPR
city: San Juan
country: Puerto Rico
facility: PROncology
city: San Juan
country: Puerto Rico
facility: San Juan City Hospital
Study officials:
References: