Cancer of BreastPhase 2NCT02642094

Aging Mammary Stem Cells and Breast Cancer Prevention

A Phase 2 study testing Rapamycin in people with Cancer of Breast, run by LuZhe Sun at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial summary

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

Who is it for?: Ages 18 to 80 years, women only
Conditions the study is for: Cancer of Breast
What is being tested?: Rapamycin
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 58 participants
Where: 1 siteUnited States
Study dates: Jul 2016to 1 May 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 15Show fewer

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:
Leukocytes ≥ 3,000/uL
Absolute neutrophil count ≥ 1,500/uL
Platelets ≥ 100,000/uL
AST ≤ 2.5 X ULN
ALT ≤ 2.5 X ULN
Total bili ≤ 1.5 X ULN or Direct bili ≤ 1 X ULN

Who cannot join

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.

Show all 14Show fewer

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:
GI tract disease resulting in an inability to take oral medication
Malabsorption syndrome
Require IV alimentation
History of prior surgical procedures affecting absorption
Uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Texas Health Science Center San Antonio
San Antonio, Texas, 78229

Other trials in United States

About this study

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

Read the 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
Being tested: Rapamycin
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RapamycinDrug
Also called Sirolimus
Low dose of rapamycin at 2 mg/day for -5-7 days of treatment

Study groups in NCT02642094
Study group	Role	What they receive
The effect of short-term rapamycin treatment	Experimental	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. Receives: Drug: Rapamycin

What is being measured

The primary outcome is the main question the study is designed to answer.

The Effect of Short-term Rapamycin Treatment on Biomarker Ki67 Associated With Progression to Invasive Breast Cancer
Comparing biopsy tissues before the treatment with surgical samples after rapamycin treatment in the same individuals to determine percentage nuclei with positive staining for Ki67 in the CCIS lesions.
Measured: Baseline to 5-7 day rapamycin plus 3-7 day washout
The Effect of Short-term Rapamycin Treatment on the Frequency of Luminal Progenitor Epithelial Cells
Assessment will be used to measure changes in luminal progenitor cell population between controls and treated patients.
Measured: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.
The Effect of Short-term Rapamycin Treatment on Sphere Formation Efficiency of Mammary Stem Cells
Measurement of difference in sphere formation efficiency (SFE) by mammary stem cells (MaSCs) in the basal myoepithelial cell population between the control and treatment groups. SFE is an in vitro method by quantifying the number of spheres formed divided by the number of cells seeded. Higher SFE indicates higher frequency of MaSCs.
Measured: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.
The Effect of Short-term Rapamycin Treatment on the Frequency of Mature Luminal Epithelial Cells
Measurement of Mature luminal cell populations in the treatment group compared to the control group.
Measured: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.
The Effect of Short-term Rapamycin Treatment on Sphere Formation Efficiency of Luminal Progenitor Cells
The measurement of sphere formation efficiency (SFE) between luminal progenitor (LP) cells from the control group and those from the treatment group. SFE is an in vitro method by quantifying the number of spheres formed divided by the number of cells seeded. Higher SFE indicates higher frequency of LP cells.
Measured: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 20161 May 2022

First posted30 Dec 2015 (estimated)
Study startJul 2016
Primary completion1 Mar 2022
Study completion1 May 2022

Why it stopped: The study was terminated early according to the protocol due to efficacy.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Cancer of BreastStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 58 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02642094
Sponsor's protocol ID: CTMS 15-2096
Other IDs: 1R01CA192564-01A1
Status last verified: Dec 2023
First submitted: 25 Nov 2015
Last updated: 5 Dec 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes

Publications

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.
PubMed 37904250

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

All Cancer of Breast trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Aging Mammary Stem Cells and Breast Cancer Prevention
ClinicalTrials.gov ID: NCT02642094
Acronym / sponsor ID: CTMS 15-2096
Conditions: Cancer of Breast
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated early according to the protocol due to efficacy.
Enrolment: 58 participants (actual)
Lead sponsor: LuZhe SunUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: Jul 2016 (actual)
Primary completion: 1 Mar 2022 (actual)
Study completion: 1 May 2022 (actual)
First posted: 30 Dec 2015 (estimated)
Results: Posted 5 Dec 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
The effect of short-term rapamycin treatment	Experimental	Drug: RapamycinSubjects 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.

Who may qualify

Ages: 18 to 80 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

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.

Key exclusion criteria (14 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RapamycinAlso: SirolimusLow dose of rapamycin at 2 mg/day for -5-7 days of treatment	Drug	The effect of short-term rapamycin treatment

Primary outcome

The Effect of Short-term Rapamycin Treatment on Biomarker Ki67 Associated With Progression to Invasive Breast Cancer
Time frame: Baseline to 5-7 day rapamycin plus 3-7 day washout
Comparing biopsy tissues before the treatment with surgical samples after rapamycin treatment in the same individuals to determine percentage nuclei with positive staining for Ki67 in the CCIS lesions.
The Effect of Short-term Rapamycin Treatment on the Frequency of Luminal Progenitor Epithelial Cells
Time frame: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.
Assessment will be used to measure changes in luminal progenitor cell population between controls and treated patients.
The Effect of Short-term Rapamycin Treatment on Sphere Formation Efficiency of Mammary Stem Cells
Time frame: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.
Measurement of difference in sphere formation efficiency (SFE) by mammary stem cells (MaSCs) in the basal myoepithelial cell population between the control and treatment groups. SFE is an in vitro method by quantifying the number of spheres formed divided by the number of cells seeded. Higher SFE indicates higher frequency of MaSCs.
The Effect of Short-term Rapamycin Treatment on the Frequency of Mature Luminal Epithelial Cells
Time frame: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.
Measurement of Mature luminal cell populations in the treatment group compared to the control group.
The Effect of Short-term Rapamycin Treatment on Sphere Formation Efficiency of Luminal Progenitor Cells
Time frame: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.
The measurement of sphere formation efficiency (SFE) between luminal progenitor (LP) cells from the control group and those from the treatment group. SFE is an in vitro method by quantifying the number of spheres formed divided by the number of cells seeded. Higher SFE indicates higher frequency of LP cells.

Results and safety

Results posted to the registry on 5 Dec 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Rapamycin Treatment Group	40	38
Un-treated Control Group	18	18

Primary outcome: The Effect of Short-term Rapamycin Treatment on Biomarker Ki67 Associated With Progression to Invasive Breast Cancer

Time frame: Baseline to 5-7 day rapamycin plus 3-7 day washout. Mean (Standard Deviation). Unit: percentage of Ki67+ cells

Measure	Effect of Short-term Rapamycin Treatment on Biomarker Ki67 n = 12
Pre-treatment	8.235 (5.848)
Post-treatment	3.666 (3.176)

Effect of Short-term Rapamycin Treatment on Biomarker Ki67: p = 0.0020, t-test, 2 sided

Population analysed: Tissue samples were randomly selected from 12 patients with DCIS who participated in the treatment study

Primary outcome: The Effect of Short-term Rapamycin Treatment on the Frequency of Luminal Progenitor Epithelial Cells

Time frame: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.. Mean (Standard Deviation). Unit: percentage of total lineage neg. cells

Measure	Control n = 18	Treatment Group n = 27
Value	11.82 (9.221)	6.178 (5.525)

Control vs Treatment Group: p = 0.0137, t-test, 2 sided

Population analysed: We were only able to obtain fresh surgical tissues and mammary epithelial cell profiles by flowcytometry from 27 patients in the treatment group. The mean data of luminal progenitor cells were compared between the control and treatment groups with unpaired t test.

Primary outcome: The Effect of Short-term Rapamycin Treatment on Sphere Formation Efficiency of Mammary Stem Cells

Time frame: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.. Mean (Standard Deviation). Unit: spheres formed per 1,000 cells

Measure	Control n = 18	Treatment Group n = 22
Value	3.681 (2.303)	0.717 (1.414)

Control vs Treatment Group: p <0.0001, t-test, 2 sided

Population analysed: We were only able to obtain fresh surgical tissues and mammary epithelial cell profiles by flowcytometry from 27 patients in the treatment group. Out of the 27, only 22 samples yielded enough basal myoepithelial cells for the quantification of the SFE. Comparison between control group and treatment group.

Primary outcome: The Effect of Short-term Rapamycin Treatment on the Frequency of Mature Luminal Epithelial Cells

Time frame: 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group.. Mean (Standard Deviation). Unit: percentage of total lineage neg. cells

Measure	Control n = 18	Treatment Group n = 27
Value	11.82 (9.221)	6.178 (5.525)

Control vs Treatment Group: p = 0.0072, t-test, 2 sided

Population analysed: We were only able to obtain fresh surgical tissues and mammary epithelial cell profiles by flowcytometry from 27 patients in the treatment group.

Adverse events

Time frame: 1 month. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Rapamycin Treatment	0 of 40 (0%)	24 of 40 (60%)	0 of 40

Limitations and caveats (from the sponsor): Our hypothesis was that a low dose and short term treatment with rapamycin in patients with early stage breast cancer would show significantly attenuation of mammary stem and progenitor cell activity and tumor progression biomarkers in a non-randomized study.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37904250Bouamar 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.

Related trials for Cancer of Breast

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

LuZhe Sun, PhD principal investigator

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

Ismail Jatoi, MD principal investigator

The University of Texas Health Science Center at San Antonio

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rapamycin in people with Cancer of Breast, run by LuZhe Sun at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Effect of Short-term Rapamycin Treatment on Biomarker Ki67 Associated With Progression to Invasive Breast Cancer (time frame: Baseline to 5-7 day rapamycin plus 3-7 day washout). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02642094, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2023.