Clinical trial NCT06364267: Low Dose Exemestane vs Low Dose Tamoxifen in Post-menopausal Women at High Risk for Breast Cancer.
Official title: Randomized Double Blind Phase II Trial of Baby Exemestane vs Baby Tamoxifen in Post-menopausal Women at High Risk for Breast Cancer.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast cancer, menopause, exemestane, tamoxifen, MenQol, Low dose
babytam, babyexe
Lead sponsor: Ente Ospedaliero Ospedali Galliera
Sponsor class: OTHER
Collaborators: name: Dana-Farber/Brigham and Women's Cancer Center
name: Herbert Irving Comprehensive Cancer Center
name: Istituto Europeo di Oncologia
name: Breast Cancer Research Foundation
First posted: 2024-04-15
Enrollment: 140
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to to compare low dose of exemestane (babyexe) versus low dose of tamoxifen (babytam) in terms of change of quality of life from baseline to 12 months.

Detailed description: This is a multicenter, randomized, double blind phase II trial.

Eligible patients will be randomized in a 1:1 ratio to:

ARM 1: BabyEXE Arm, 25 mg eod, typically every odd day of the monthly calendar for 12 monthsor unless progression, SAE, medical decision, patient withdrawal occur.

ARM 2: BabyTAM Arm, 10 mg eod, typically every odd day of the monthly calendar for 12 months or unless progression, SAE, medical decision, patient withdrawal occur.

Blinding will be guaranteed by over-encapsulation of active tablet agents with an AA capsule in a 6-month bottle.

In both arms, treatment should begin within 30 days from randomization. Exemstane and Tamoxifen will be provided for free by the Study Sponsor.

After study completion, participants will be unblinded and treated according to local guidelines. Clinical visit will be performed every 6 months (±14 days) with physical examination vital signs and weight and girth measurement, ECOG PS, MENQOL questionnaire (0, 6, 12 months), review of self-reported compliance, concomitant medications, AEs assessment, and physical exam. Telephone/video contact may be allowed at 3 and 9 months, whereas baseline, 6 months and 12 months visits are necessary for blood collection and biomarker assessment. Blood serum for centralized storage at IEO, Milan, Italy, will be collected at different time points.

Eligibility criteria: Inclusion Criteria:

1. Postmenopausal state is defined 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. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

   Any of the following criteria must be met:
   1. 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) or diagnosis within 3 years of HRL (ADH, LCIS, ALH), or:
   2. 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:
   3. 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.
2. Eastern Cooperative Oncology Group - Performance Status (ECOG-PS) 0-1.
3. Able to swallow oral medications.
4. 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.
5. Ability to understand and the willingness to sign a written informed consent document.
6. Mammography performed up to 6 months before the trial consent form signature.
7. DEXA performed up to 12 months before the trial consent form signature.
8. Patients with life expectancy ≥ 10 years.
9. Patients with normal liver function tests and blood cell count.
10. Negative gynaecological examination performed up to 6 months before the trial consent form signature.

Exclusion Criteria:

1. Pre/perimenopausal women
2. History of DVT or PE.
3. Endometrial cancer.
4. Macular disorders.
5. Inability to comply with study procedures.
6. Prior use of antiestrogens within 12 months from the date of the trial consent form signature.
7. Use of hormone replacement therapy (HRT) within 3 months from the date of the trial consent form signature.
8. Severe osteoporosis (T score ≤ 2.5 at either spine or hip), or recent vertebral fracture (within 6 months) not treated with zolendronic acid or denosumab.
9. Use of terbinafine, quinidine, cinacalcet, rifampicin, phenytonin, carbamazepine, phenobarbital, and St. John's wort, warfarin, erythromycin, cyclosporin, nifepidine and any concomitant coumarin-type anticoagulant therapy.
10. Patients with moderate or severe renal impairment.
11. Patients with a known hypersensitivity to study drugs.

Primary outcomes:
measure: Quality of life MEnQol
timeFrame: 12 months
Secondary outcomes:
measure: Sex hormones
timeFrame: 12 months
measure: MenQol score domain
timeFrame: 6 months
measure: Sex hormones
timeFrame: 6 months
measure: Other domains of MenQol
timeFrame: 6 and 12 months
measure: Safety profile
timeFrame: 6 and 12 months
measure: PMAS
timeFrame: 6 and 12 months
measure: BPI
timeFrame: 6 and 12 months
measure: Bone biomarker
timeFrame: 6 and 12 months
measure: Customer satisfatcion
timeFrame: Screening
measure: Exemestane toxicity
timeFrame: 12 months
Other outcomes:
measure: MMG risk score
timeFrame: 12 months
measure: MMG density
timeFrame: 12 months
measure: HOMA
timeFrame: 6 and 12 months
measure: Hs-CRP
timeFrame: 6 and 12 months
measure: Adipokines
timeFrame: 6 and 12 months
measure: Bone density
timeFrame: 12 months
measure: BMI
timeFrame: 6 and 12 months
measure: Other biomarkers
timeFrame: 6 and 12 months
Locations:
city: Genova
country: Italy
facility: E.O. Ospedali Galliera
Study officials:
affiliation: Ente Ospedaliero Ospedali Galliera
name: Andrea U De Censi, MD
role: STUDY_CHAIR
References: