Aging Mammary Stem Cells and Breast Cancer Prevention

• ClinicalTrials.gov Identifier: NCT02642094
• Recruitment Status: Active, not recruiting
• First Posted: December 30, 2015
• Last Update Posted: March 8, 2022
• Sponsor: LuZhe Sun
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): LuZhe Sun, The University of Texas Health Science Center at San Antonio

Tracking Information

• First Submitted Date: November 25, 2015
• First Posted Date: December 30, 2015
• Last Update Posted Date: March 8, 2022
• Actual Study Start Date: July 2016
• Actual Primary Completion Date: February 28, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 5, 2016): The effect of short-term rapamycin treatment on tumor grade and biomarkers associated with progression to invasive breast cancer [ Time Frame: Tissue samples will be collected 10 days after rapamycin dose for analysis. ]
• Original Primary Outcome Measures (submitted: December 29, 2015): Luminal-to-basal epithelial ratio - The number of luminal cells divided by the number of basal cells in breast tissue specimens to address whether this ratio will change during aging. [ Time Frame: Tissue samples will be collected over a 5 year period and analysed. ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: October 5, 2016)

• The effect of short-term rapamycin treatment on the presence or absence of necrosis [ Time Frame: A tissue sample will be collected 10 days after rapamycin dose for analysis. ]
• The effect of short-term rapamycin treatment on luminal-to-basal epithelial ratio [ Time Frame: A tissue sample will be collected 10 days after rapamycin dose for analysis. ]
• The effect of short-term rapamycin treatment on basal and luminal stem/progenitor cell frequency [ Time Frame: A tissue sample will be collected 10 days after rapamycin dose for analysis. ]
• The effect of short-term rapamycin treatment on sphere regeneration frequency in serial passages [ Time Frame: A tissue sample will be collected 10 days after rapamycin dose for analysis. ]

Original Other Pre-specified Outcome Measures (submitted: December 29, 2015)

• Basal and luminal stem/progenitor cell frequency, which will examine the percentage of luminal or basal cells that are capable of forming spheres in culture, and whether these frequencies will change during aging. [ Time Frame: Tissue samples will be collected over a 5 year period for analysis. ]
• Sphere regeneration frequency in serial passages - will examine the self-renewal capacity of the stem and progenitor cells that are capable of forming spheres in suspension culture and in Matrigel culture, and can re-form the spheres. [ Time Frame: Tissue samples will be collected over a 5 year period for analysis. ]
• The effect of short-term rapamycin treatment on the number of mammary gland ducts with DCIS or ADH. [ Time Frame: A tissue sample will be collected 10 days after rapamycin dose for analysis. ]
• The effect of short-term rapamycin treatment on tumor grade [ Time Frame: A tissue sample will be collected 10 days after rapamycin dose for analysis. ]
• The effect of short-term rapamycin treatment on the presence or absence of necrosis [ Time Frame: A tissue sample will be collected 10 days after rapamycin dose for analysis. ]
• The effect of short-term rapamycin treatment on luminal-to-basal epithelial ratio [ Time Frame: A tissue sample will be collected 10 days after rapamycin dose for analysis. ]
• The effect of short-term rapamycin treatment on basal and luminal stem/progenitor cell frequency [ Time Frame: A tissue sample will be collected 10 days after rapamycin dose for analysis. ]
• The effect of short-term rapamycin treatment on sphere regeneration frequency in serial passages [ Time Frame: A tissue sample will be collected 10 days after rapamycin dose for analysis. ]

Descriptive Information

• Brief Title: Aging Mammary Stem Cells and Breast Cancer Prevention
• Official Title: Aging Mammary Stem Cells and Breast Cancer Prevention
• 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
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Cancer of Breast

Intervention

Drug: Rapamycin

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

Other Name: Sirolimus

Study Arms

Experimental: 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.

Intervention: Drug: Rapamycin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 6, 2022): 40
• Original Estimated Enrollment (submitted: December 29, 2015): 60
• Estimated Study Completion Date: August 2022
• Actual Primary Completion Date: February 28, 2022 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02642094
• Other Study ID Numbers: CTMS 15-2096; 1R01CA192564-01A1 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: LuZhe Sun, The University of Texas Health Science Center at San Antonio
• Original Responsible Party: LuZhe Sun, The University of Texas Health Science Center at San Antonio, Principal Investigator
• Current Study Sponsor: LuZhe Sun
• Original Study Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: LuZhe Sun, PhD; University of Texas Health Science Center San Antonio, Co-PI
• Principal Investigator: Ismail Jatoi, MD; University of Texas Health Science Center San Antonio

• PRS Account: The University of Texas Health Science Center at San Antonio
• Verification Date: March 2022