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Clinical Trial NCT07499999 (BabyTEARS) for Breast Cancer, Ductal Carcinoma, Estrogen-receptor-positive Breast Cancer, Atypical Lobular Hyperplasia, BRCA2 Mutation, CHEK2 Gene Mutation, Ataxia Telangiectasia Mutated Gene Mutation is not yet recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here. | ||
Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer (BabyTEARS) Phase 2 140 Randomized Double-Blind
The goal of this research study is to evaluate the efficacy and safety of low-dose exemestane versus low-dose tamoxifen in post-menopausal women at high risk for breast cancer.
The names of the study drugs involved in this study are:
- Exemestane (a type of steroidal aromatase inhibitor)
- Tamoxifen (a type of selective estrogen receptor modulator)
Participants will be r...
Show MoreRandomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer (BabyTEARS)
- BabyTEARS
- 25-550
High Risk Breast Cancer
Cancer Prevention
Ductual Carcinoma in Site
Estrogen Receptor Positive
High Risk Lesions
HRL
Atypical Lobular Hyperplasia
BRCA2
CHEK2
ATM
| Participant Group/Arm | Intervention/Treatment |
|---|---|
ExperimentalLow-Dose Exemestane Participants will be randomized 1:1 with a permuted-block technique and stratified by center and will complete:
* Baseline visit with assessments
* Predetermined dose of Exemestane 1x on every odd day for 12 months
* 3 month in-clinic visit
* 6 month in-clinic visit
* 9 month in-clinic visit
* 12 month end of intervention in-clinic visit
* Follow up for 12 months | Exemestane A steroidal aromatase inhibitor, blinded capsules taken orally, per protocol. |
ExperimentalLow-Dose Tamoxifen Participants will be randomized 1:1 with a permuted-block technique and stratified by center and will complete:
* Baseline visit with assessments
* Predetermined dose of Tamoxifen 1x on every odd day for 12 months
* 3 month in-clinic visit
* 6 month in-clinic visit
* 9 month in-clinic visit
* 12 month end of intervention in-clinic visit
* Follow up for 12 months | Tamoxifen A selective estrogen receptor modulator, blinded capsules taken orally, per protocol. |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Difference in Overall Domain Score Change From Baseline in Menopause-Specific Quality of Life Questionnaire (MENQOL) Between the Two Arms at 12 Months | The MENQOL assesses the degree to which menopausal symptoms are troublesome in four domains: vasomotor (three items), sexual (three items), physical (seven items), and psychosocial (16 items). Each item is answered with Yes or No. If the response is Yes, the participant rates how bothersome the symptom was on a scale from 0 to 6, where 0 indicates "not at all bothered" and 6 indicates "extremely bothered." For each participant, the difference between the baseline and 12-month overall MENQOL score will be calculated and defined as the "change." | 12 Months |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Difference of Free Estradiol Levels between Two Arms at 12 Months | Free estradiol concentration in blood will be measured to compare the hormonal effects of babyexe versus babytam. | 12 Months |
Difference of Estradiol/Sex Hormone Binding Globulin (SHBG) Levels between Two Arms at 12 Months | The estradiol/SHBG ratio will be calculated as total estradiol divided by SHBG to evaluate differences in hormonal effects between babyexe and babytam. | 12 Months |
Difference of Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Levels Between Two Arms at 12 Months | Blood levels of IGF-I will be measured to compare the effects of babyexe and babytam on IGF-I. | 12 Months |
Insulin-like Growth Factor I (IGF-I)/Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Ratio Between Two Arms at 12 Months | The ratio of IGF-I to IGFBP-3 in blood will be calculated to compare the effects of babyexe and babytam on IGF system balance. | 12 Months |
Overall Domain Score Change From Baseline in Menopause-Specific Quality of Life Questionnaire (MENQOL) at 6 Months | The MENQOL assesses the degree to which menopausal symptoms are troublesome in four domains: vasomotor (three items), sexual (three items), physical (seven items), and psychosocial (16 items). Each item is answered with Yes or No. If the response is Yes, the participant rates how bothersome the symptom was on a scale from 0 to 6, where 0 indicates "not at all bothered" and 6 indicates "extremely bothered." For each participant, the difference between the baseline and 6-month overall MENQOL score will be calculated and defined as the "change." | 6 months |
Free Estradiol Levels | Free estradiol concentration in blood will be measured to compare the hormonal effects of babyexe versus babytam. | 6 Months |
Estradiol/Sex Hormone Binding Globulin (SHBG) Levels | The estradiol/SHBG ratio will be calculated as total estradiol divided by SHBG to evaluate differences in hormonal effects between babyexe and babytam. | 6 months |
Insulin-like Growth Factor I (IGF-I) Levels | Blood levels of IGF-I will be measured to compare the effects of babyexe and babytam on IGF-I. | 6 months |
Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Levels | Blood levels of IGFBP-3 will be measured to compare the effects of babyexe and babytam on IGFBP-3. | 6 months |
Insulin-like Growth Factor I (IGF-I)/Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Ratio | The ratio of IGF-I to IGFBP-3 in blood will be calculated to compare the effects of babyexe and babytam on IGF system balance. | 6 months |
Physical Domain Score Change From Baseline in Menopause-Specific Quality of Life Questionnaire (MENQOL) Between the Two Arms at 6 Months and 12 months | The MENQOL physical domain, which includes seven items, assesses the degree to which physical menopausal symptoms are troublesome. Each item is answered with Yes or No. If the response is Yes, the participant rates how bothersome the symptom was on a scale from 0 ("not at all bothered") to 6 ("extremely bothered"). For each participant, the difference between the baseline and 6-month physical domain MENQOL score will be calculated and defined as the "change." | 6 months and 12 months |
Sexual Domain Score Change From Baseline in Menopause-Specific Quality of Life Questionnaire (MENQOL) | The MENQOL sexual domain, which includes three items, assesses the degree to which sexual menopausal symptoms are troublesome. Each item is answered with Yes or No. If the response is Yes, the participant rates how bothersome the symptom was on a scale from 0 ("not at all bothered") to 6 ("extremely bothered"). For each participant, the difference between the baseline and 6-month sexual domain MENQOL score will be calculated and defined as the "change." | 6 months and 12 months |
Psychosocial Domain Score Change From Baseline in Menopause-Specific Quality of Life Questionnaire (MENQOL) | The MENQOL psychosocial domain, which includes sixteen items, assesses the degree to which psychosocial menopausal symptoms are troublesome. Each item is answered with Yes or No. If the response is Yes, the participant rates how bothersome the symptom was on a scale from 0 ("not at all bothered") to 6 ("extremely bothered"). For each participant, the difference between the baseline and 6-month psychosocial domain MENQOL score will be calculated and defined as the "change." | 6 months and 12 months |
Vasomotor Domain Score Change From Baseline in Menopause-Specific Quality of Life Questionnaire (MENQOL) | The MENQOL vasomotor domain, which includes three items, assesses the degree to which vasomotor menopausal symptoms are troublesome. Each item is answered with Yes or No. If the response is Yes, the participant rates how bothersome the symptom was on a scale from 0 ("not at all bothered") to 6 ("extremely bothered"). For each participant, the difference between the baseline and 6-month vasomotor domain MENQOL score will be calculated and defined as the "change." | 6 months and 12 months |
Global Adverse Event (AE) Rate | Global AE rate is defined as the proportion of participants who experience any AE. AE is summarized and graded based on CTCAE v 5.0. | 12 Months |
Grade 2 or Higher Adverse Event (AE) Rate | Grade 2 or higher AE rate is defined as the proportion of participants who experience grade 2 or higher AE. AE is summarized and graded based on CTCAE v 5.0. | 12 months |
Grade 3 or Higher Adverse Event (AE) Rate | Grade 3 or higher AE rate is defined as the proportion of participants who experience grade 2 or higher AE. AE is summarized and graded based on CTCAE v 5.0. | 12 months |
Distribution of Maximum Adverse Event Grade per Participant | The maximum adverse event (AE) grade experienced by each participant during the treatment period will be summarized to characterize the overall toxicity profile. Adverse events will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. For each participant, the highest AE grade observed at any time during the treatment period will be identified, and the distribution of these maximum grades across participants will be reported, in accordance with the statistical considerations for toxicity evaluation described in Section 16.15 of the protocol. | 12 months |
Medication Adherence Assessed by PMAS | Medication adherence will be assessed using the PMAS instrument, as specified in Appendix H of the protocol. PMAS is a validated wording-based adherence scale and does not generate a continuous numeric summary score. Therefore, adherence will be operationalized categorically, consistent with its original validation methodology. Participants will be classified into predefined adherence categories based on their item responses (e.g., high adherence versus non-high adherence). Adherence will be summarized as the proportion of participants meeting the definition of "high adherence" within each treatment arm. Between-arm comparisons will be based on categorical distributions rather than mean or continuous scores, in accordance with Sections 9.10-9.11 of the protocol. | 6 months and 12 months |
BPI (Brief Pain Inventory) Score Change from Baseline | Pain will be assessed using BPI, a validated questionnaire that measures both pain intensity and the degree to which pain interferes with daily activities. Each item is scored from 0 to 10, with higher scores indicating worse pain or greater interference. | 6 months and 12 months |
C-Telopeptide Levels | Blood levels of C-telopeptide, a marker of bone resorption, will be measured assess changes in bone turnover. | 6 months and 12 months |
Postmenopausal state is defined⁸ as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy.
Any of the following criteria must be met:
- Recent (within 12 months from date of consent form signature) histologic diagnosis of ER+ve (>5%) DCIS (patients with DCIS should have undergone breast-conserving therapy i.e. lumpectomy to remove the tumor with negative surgical margins followed by radiotherapy (see footnote 1 below)) diagnosis within 3 years of HRL (ADH, LCIS, ALH), or;
- At least 3% breast cancer risk at 5 years (or 5% risk at 10yrs) per one of the following risk models: the Breast Cancer Surveillance Consortium risk calculator V3 or Tyrer-Cuzick model V8 or;
- Known carriers of a germline pathogenic/likely pathogenetic variant in the following moderate penetrance genes (CHEK2 or ATM), or women with chest wall irradiation before age of 30 years
Eastern Cooperative Oncology Group - Performance Status (ECOG-PS) 0-1
Able to swallow oral medications
Participants 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. Specifically, all cancers diagnosed since 3 years or longer except for breast and endometrial are eligible.
Ability to understand and the willingness to sign a written informed consent document
Mammography performed up to 6 months before the trial consent form signature
DEXA performed up to 12 months before the trial consent form signature
Life expectancy ≥ 10 years
Normal liver function tests and blood cell count
Negative gynecological examination performed up to 6 months before the trial consent form signature.
ᶥ While DCIS and ADH are routinely excised, and treatment of DCIS often includes radiotherapy, lobular neoplasia (ALH and classic LCIS) are not routinely excised in most US centers unless radiologic-pathologic findings are discordant given the very low risk of an associated cancer.11,12 Participants with DCIS should have undergone breast-conserving therapy i.e. lumpectomy to remove the tumor with negative surgical margins followed by radiotherapy. All DCIS will require excision to clear margins per the SSO/ASCO/ASTRO margin guidelines for DCIS.88 In selected cases, the decision to omit RT might be taken according to low risk clinical-pathological factors (e.g., age>70, low grade, size < 1 cm, and genomic assays if available) as well as patient preference after full discussion of the risks and benefits.
- Pre/perimenopausal women: exemestane is only effective in post-menopausal women
- History of DVT or PE: tamoxifen can increase tendency to blood clot
- Endometrial cancer: full-dose tamoxifen is associated with increased risk of endometrial cancers
- Macular disorders: tamoxifen is associated with retinal damage
- Inability to comply with study procedures: standard
- Prior use of antiestrogens within 12 months from the date of the trial consent form signature: there can be long duration effects from antiestrogens that could influence trial drug effects
- Use of hormone replacement therapy (HRT) within 3 months from the date of the trial consent form signature: similarly, wish to avoid any long lasting effect before alternate effect from study drugs
- Severe osteoporosis (T score ≤ 2.5 at either spine or hip), or recent vertebral fracture (within 6 months) not treated with zoledronic acid or denosumab: Exemestane is an aromatase inhibitor which can worsen bone loss (osteoporosis)
- Current use of terbinafine, quinidine, cinacalcet, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort, warfarin, erythromycin, cyclosporin, nifedipine and any concomitant coumarin-type anti-coagulant therapy: these drugs compete for the Cytochrome P450 metabolic pathways of tamoxifen and exemestane
- Moderate or severe renal impairment: Exemestane is eliminated equally by liver and renal metabolism
- Known hypersensitivity to study drugs: standard
Screening Eligibility Criteria
To register a participant to the screening phase, the following documents should be provided by the participating site:
Signed participant consent form
Postmenopausal status, and any of the following:
- Histological report of ER-positive DCIS within 12 months, or HRL of the breast within 3 years from date of consent form signature, or;
- Report of risk assessment ≥3% in 5 years or 5% in 10 years of breast cancer according to the selected risk model(s) different criteria within 6 months from screening, or;
- Documentation of women carriers of a germline pathogenic/likely pathogenetic variant in a moderate penetrance gene (CHEK2 or ATM), or;
- Documented history of chest wall radiotherapy before age 30.
Inclusion of Women and Minorities
Only women will be recruited in the study given that breast cancer is much more frequent in women than men and because exemestane is contraindicated in men because of risk of uncontrolled gonadal stimulation. Women of all races and ethnic groups are eligible for this trial. At participating sites, efforts will be made to enroll women from diverse ethnic and socio-economic backgrounds, including recruitment of non-white women in a selected New York city area.
NIH policy requires that women and members of minority groups and their subpopulations be included in all NIH-supported biomedical and behavioral research projects involving NIH-defined clinical research unless a clear and compelling rationale and justification establishes to the satisfaction of the funding Institute & Center (IC) Director that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. Exclusion under other circumstances designated by the Director, NIH, upon the recommendation of an IC Director based on a compelling rationale and justification. Cost is not an acceptable reason for exclusion except when the study would duplicate data from other sources. Women of childbearing potential should not be routinely excluded from participation in clinical research.
Dana-Farber Cancer InstituteBreast Cancer Research FoundationMassachusetts