Aging Mammary Stem Cells and Breast Cancer Prevention

NCT ID: NCT02642094

Last Updated: 2023-12-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2022-05-01

Brief Summary

To examine whether rapamycin can reduce malignant markers and aberrant mammary stem/progenitor cells (MaSCs) number in surgical specimens

Detailed Description

A non-randomized, open-label, phase II, window of opportunity trial will be carried out to see if a 5-7 day rapamycin treatment can reduce malignant markers and aberrant MaSC number

Conditions

Cancer of Breast

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

The effect of short-term rapamycin treatment

Subjects will be given a low dose of rapamycin at 2 mg/day for 5-7 days of treatment. A surgical specimen will be taken 3-7 days after the last dose of rapamycin. The specimens will be evaluated for lesion size, nuclear grade, presence of necrosis in each patient's core biopsy and surgical specimens, as well as IHC (ImmunoHistoChemistry) for biomarkers including p16, COX2 (cyclooxygenase-2), and Ki-67. Specimens will also be tested for rapamycin treatment on the properties of mammary stem/progenitor cells as another biomarker for gauging the efficacy of rapamycin treatment.

Group Type: EXPERIMENTAL

Rapamycin

Intervention Type: DRUG

Low dose of rapamycin at 2 mg/day for -5-7 days of treatment

Interventions

Rapamycin

Low dose of rapamycin at 2 mg/day for -5-7 days of treatment

Intervention Type: DRUG

Other Intervention Names

Sirolimus

Eligibility Criteria

Inclusion Criteria

• Women with confirmed menopausal status. All patients who have NOT had a prior bilateral oophorectomy and/or are younger than age 60, will require menopausal status verified by FSH and estradiol local labs.
• Women diagnosed with DCIS/LCIS, Atypical lobular hyperplasia (ALH) or ADH lesions detected by pathology
• Women scheduled for mastectomy or lumpectomy after DCIS/LCIS, ALH or ADH diagnosis
• Women consented to the UT Health Cancer Center MD Anderson Cancer Center tissue biorepository (HSC20070684H)
• Women of child-bearing potential willing to practice 2 forms of contraception, one of which must be a barrier method until at least 30 days after the last dose of rapamycin.
• Women of child-bearing potential must have a negative serum pregnancy test at time of enrollment.
• Patients must be able to swallow and retain oral medication.
• All patients must have given signed informed consent prior to registration on study.
• Patients must have normal organ and marrow function as defined below:

1. Leukocytes ≥ 3,000/uL

2. Absolute neutrophil count ≥ 1,500/uL

3. Platelets ≥ 100,000/uL

4. AST ≤ 2.5 X ULN

5. ALT ≤ 2.5 X ULN

6. Total bili ≤ 1.5 X ULN or Direct bili ≤ 1 X ULN

Exclusion Criteria

• Women who are pregnant.
• Women who are receiving any other concomitant treatment for their DCIS/LCIS, ALH or ADH
• Women who are taking rapamycin for another diagnosis.
• Women with an allergy to rapamycin or its derivatives.
• Active infection requiring systemic therapy.
• Patients who are taking any pills containing herbal (alternative) medicines are NOT eligible for participation. Patients must be off any such medications by the time of registration.
• Immunocompromised subjects, including patients with human immunodeficiency virus
• Women currently taking strong CYP3A4 inducers or inhibitors. Drugs that cannot be coadministered with rapamycin include but are not limited to: Calcium channel blockers: nicardipine, Antifungal agents: clotrimazole, fluconazole, Antibiotics: troleandomycin, Gastrointestinal prokinetic agents: cisapride, metoclopramide, Other drugs: bromocriptine, cimetidine, danazol, HIV-protease inhibitors (e.g., ritonavir, indinavir), Anticonvulsants: carbamazepine, phenobarbital, phenytoin, Antibiotics: rifapentine. The research team can provide a full list of these medications.
• Patients with any of the following conditions or complications are NOT eligible for participation:

1. GI tract disease resulting in an inability to take oral medication

2. Malabsorption syndrome

3. Require IV alimentation

4. History of prior surgical procedures affecting absorption

5. Uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

LuZhe Sun

OTHER

Sponsor Role: lead

Responsible Party

LuZhe Sun

Co-Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

LuZhe Sun, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Health Science Center San Antonio, Co-PI

Ismail Jatoi, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Health Science Center San Antonio

Locations

University of Texas Health Science Center San Antonio

San Antonio, Texas, United States

Countries

United States

References

Bouamar H, Broome LE, Lathrop KI, Jatoi I, Brenner AJ, Nazarullah A, Gorena KM, Garcia M, Chen Y, Kaklamani V, Sun LZ. mTOR inhibition abrogates human mammary stem cells and early breast cancer progression markers. Breast Cancer Res. 2023 Oct 30;25(1):131. doi: 10.1186/s13058-023-01727-z.

Reference Type: DERIVED

PMID: 37904250 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R01CA192564-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CTMS 15-2096

Identifier Type: -

Identifier Source: org_study_id