Clinical trial NCT02642094: Aging Mammary Stem Cells and Breast Cancer Prevention
Official title: Aging Mammary Stem Cells and Breast Cancer Prevention
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cancer of Breast
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2015-12-30
Enrollment: 58
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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

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)

Primary outcomes:
measure: The Effect of Short-term Rapamycin Treatment on Biomarker Ki67 Associated With Progression to Invasive Breast Cancer
timeFrame: Baseline to 5-7 day rapamycin plus 3-7 day washout
measure: The Effect of Short-term Rapamycin Treatment on the Frequency of Luminal Progenitor Epithelial Cells
timeFrame: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.
measure: The Effect of Short-term Rapamycin Treatment on Sphere Formation Efficiency of Mammary Stem Cells
timeFrame: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.
measure: The Effect of Short-term Rapamycin Treatment on the Frequency of Mature Luminal Epithelial Cells
timeFrame: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.
measure: The Effect of Short-term Rapamycin Treatment on Sphere Formation Efficiency of Luminal Progenitor Cells
timeFrame: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.
Secondary outcomes:
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: University of Texas Health Science Center San Antonio
state: Texas
Study officials:
affiliation: University of Texas Health Science Center San Antonio, Co-PI
name: LuZhe Sun, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas Health Science Center San Antonio
name: Ismail Jatoi, MD
role: PRINCIPAL_INVESTIGATOR
References: