Babytam vs Babyexe in Post-menopausal Women at High Risk for Breast Cancer. (BabyTears)

Randomized Double Blind Phase 2 Trial of Baby Tamoxifen Versus Baby Exemestane in Post-menopausal Women at High Risk for Breast Cancer. BabyTEARS (Baby Tamoxifen or Exemestane Assessment Randomized Study)

The purpose of the study is to determine if 6 and 12 months of treatment with Tamoxifen at lower dose is superior to Exemestane at lower dose on quality of life.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tamoxifen 10 MG; Drug: Exemestane 25 MG

Detailed Description

It is a multicenter, randomized, double blind, superiority phase IIb trial. Eligible patients will be randomized with a 1:1 ratio into:

ARM 1: 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.

ARM 2: BabyEXE Arm, 25 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. Tamoxifen and Exemestane will be provided for free by the Study Sponsor. After study completion, participants will be unblinded and treated according to local study 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 and stool collection and biomarker assessment. Blood serum and stool samples for centralized storage at IEO, Milan, Italy, will be collected at different time points.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andrea U De Censi, MD; Phone Number: +39.010.563.4501; Email: andrea.decensi@galliera.it
• Study Contact Backup: Name: Davide S Corradengo, SC; Phone Number: +39010.563.4580; Email: davide.corradengo@galliera.it

Study Locations

• Italy
  • Genova, Italy, 16128
    • E.O. Ospedali Galliera

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Postmenopausal women, defined as amenorrhea for 6-12 months and FSH> 45 mU/mL, or amenorrhea for at least 12 months, and any of the following criteria:

   • Recent (within 12 months from date of consent form signature) histologic diagnosis of ER+ve (>5%) DCIS or 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, the BCRAT model (https://tools.bcsc-scc.ucdavis.edu/BC5yearRisk/#/), or the CANRISK model (https://www.canrisk.org/), or Tyrer-CuzickmodelV8 (https://ibis-risk-calculator.magview.com/), 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.
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. Women of all races and ethnic groups are eligible for this trial.
7. Mammography performed up to 6 months before the trial consent form signature.
8. DEXA performed up to 12 months before the trial consent form signature.

9. Adequate bone marrow, hepatic and renal functions within 12 months from the date of trial consent form signature as defined below:

   1. Absolute neutrophil count (ANC) ≥ 1500/mm3
   2. Platelets ≥ 100,000/ mm3
   3. Hemoglobin ≥ 10.0 g/ dL
   4. Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN)
   5. ALT and AST ≤ 3.0 x ULN
   6. Serum creatinine ≤ 1.5 x ULN or eGFR ≥ 60 mL/ min/ 1.73 m2.

Exclusion Criteria:

• 1. Pre/perimenopausal women (amenorrhea < 6 months and FSH<45 mU/mL) are not eligible because of risk of uncontrolled ovarian stimulation with exemestane.

  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. Participants receiving any medications or substances that are inhibitors or inducers of CYP450 2D6 should be carefully assessed. Selective serotonin reuptake inhibitors (SSRIs) are allowed although should be carefully registered and discouraged in de novo users, particularly fluoxetine, paroxetine, bupropion.

  10. Certain anti-antimicrobials such as terbinafine and quinidine; and other medications like cinacalcet may reduce the effectiveness of tamoxifen.

  11. Concomitant use of CYP3A4 inducer medication (rifampicin, phenytonin, carbamazepine, phenobarbital, and St. John's wort) is contraindicated.

  12. Current use of warfarin. Antiaggregants and new oral anticoagulants are allowed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARM 1; BabyTAM Arm, 10 mg eod, typically every odd day of the monthly calendar for 12 months	Drug: Tamoxifen 10 MG; Blinded tamoxifen 10 mg every other day
Experimental: ARM 2; BabyEXE Arm, 25 mg eod, typically every odd day of the monthly calendar for 12 months.	Drug: Exemestane 25 MG; Blinded exemestane 25 mg every other day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life MEnQol	The primary endpoint is the change after 12 months of treatment between arms in the physical domain, including musculoskeletal/joint pain, of the Menopause-Specific Quality of Life Questionnaire (MENQOL), a validated tool to measure symptoms related to menopause or estrogen depletion potentially worsened by babyexe or babytam. Questionnaire scale setup: no, if yes the scale is from 0 (Not at all bothered) to 6 (extremely bothered).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other domains	Assessment of other domains of MENQOL such as vasomotor symptoms, sexual and psychological disturbances. Questionnaire scale setup: no, if yes the scale is from 0 (Not at all bothered) to 6 (extremely bothered).	12 months
PMAS questionnaire	Pill adherence through PMAS - which is the Promise Medication Adherence Scale. Questionnaire setup: scale from 1 (Strongly disagree - Never - Not at all) to 5 (Strongly agree - Always - very much)	12 months
Customer Satisfaction questionnaire	Factors related to study participation or refusal before study entry, including breast cancer-related worry and presence of life style risk factors, and participant satisfaction of study explanation. Questionnaire setup: questions about accepting/refusing the trial, and satisfaction scale from 1 (Strongly agree) to 5 (strongly disagree).	12 months
BPI	The BPI Brief Pain Inventory short form questionnaire. Querstionnaire setup: pain is evaluated from 0 (best result) to 10 (worst result).	12 months
Sex hormones biomarkers	estradiol, estrone, testosterone, androstenedione, sex hormone binding globulin	12 months
Insulin biomarker	Insulin growth factor I	12 months
Bone biomarker	C-terminal telopeptide	12 months

Collaborators and Investigators

• Sponsor: Andrea DeCensi
• Collaborators: Herbert Irving Comprehensive Cancer Center; Breast Cancer Research Foundation; Istituto Europeo di Oncologia; Dana-Farber/Brigham and Women's Cancer Center
• Investigators: Study Chair: Andrea U De Censi, MD, Ente Ospedaliero Ospedali Galliera

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: April 8, 2024
• First Submitted That Met QC Criteria: April 12, 2024
• First Posted (Actual): April 15, 2024

Study Record Updates

• Last Update Posted (Actual): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen; Exemestane
• Other Study ID Numbers: BabyTears

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No