Breast Neoplasm FemalePhase 4NCT03096418
Neoadjuvant Weekly Paclitaxel and Biomarkers of Therapy Response
A Phase 4 study testing Paclitaxel in people with Breast Neoplasm Female, run by University of Wisconsin, Madison at 2 sites in United States.
Trial summary
The hypothesis of this study is that paclitaxel levels increase chromosomal instability (CIN) in tumors and this is lethal to tumors that have pre-existing CIN. Treatment will be administered on an outpatient basis. Paclitaxel will be initiated as standard infusions on days 1, 8, and 15 of a 21-day cycle. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasm Female
- What is being tested?
- Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Mar 2017to Jun 2027
- Phase
- Phase 4
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women with pathologically demonstrated breast cancer
- Patients must be candidates for neoadjuvant paclitaxel chemotherapy by their treating oncologist. No other investigational or commercial therapeutic agents may be given concurrently with the paclitaxel.
- Patients must not have metastatic disease on staging work-up per institutional guidelines.
- A formalin-fixed paraffin embedded tumor block (preferred) or unstained slides must be available from a prior biopsy of the primary tumor (preferred) or lymph node. A minimum of 8 slides must be available.
- The primary tumor or lymph node must be readily biopsied by surgery or radiology teams.
- The primary tumor must be measurable by an imaging modality prior to treatment. This imaging modality is to be repeated after completion of 4 cycles of paclitaxel and prior to surgery. Such imaging modalities may include ultrasound, CT, mammography, or MRI. MRI will be the preferred imaging modality if available because it has the highest accuracy and positive predictive value for predicting pathologic complete response.All imaging will be performed per standard of care at the discretion of the treating physicians.
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- Subjects may not have had prior systemic chemotherapy regimens administered for treatment of their current breast cancer. However, studies (window studies, for example) that are deemed non-therapeutic, including those that utilize agents that are not FDA approved for the treatment of the patient's current breast cancer, are permitted.
- Patients must have adequate organ and marrow function as determined by the treating oncologist.
- Patient must be willing to undergo additional biopsy of breast tumor or lymph node.
- Patient must have the ability and willingness to sign a written informed consent document.
- Women of childbearing potential (per institutional policy) must agree to use effective contraception as discussed with treating oncologist for the duration of the study.
Who cannot join
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel including to other drugs formulated in Cremophor(R) EL (polyoxyethylated castor oil).
- Patients with known HIV due to concern that chemotherapy may cause further immunosuppression and potential infectious complications.
- Patients on non-aspirin anti-coagulation (Coumadin, heparins, or clopidogrel) or with documented bleeding disorders will be excluded due to risk of bleeding with biopsy.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active severe infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, other malignancies requiring therapy or psychiatric illness/social situations that would limit compliance with study requirements as determined by treatment physician.
- Pregnant women are excluded from this study because paclitaxel is a pregnancy category D drug and may cause deleterious effects to the fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with paclitaxel, breastfeeding should be discontinued if the mother is enrolled in the trial.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University of Iowa Health Care/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Mark Burkard, MD, PhD
- Recruiting
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
Cancer Connect, 800-622-8922, clinicaltrials@cancer.wisc.edu
About this study
The hypothesis of this study is that paclitaxel levels increase chromosomal instability (CIN) in tumors and this is lethal to tumors that have pre-existing CIN. Treatment will be administered on an outpatient basis. Paclitaxel will be initiated as standard infusions on days 1, 8, and 15 of a 21-day cycle. Participants will continue with paclitaxel for cycles 2-4 prior to surgery.
Read the detailed description
Primary Objectives
- To test if cancers with high chromosomal instability (CIN) respond to paclitaxel better than low CIN cancers.
Secondary Objectives
- To identify patient-specific differences in tumor levels and distribution of paclitaxel at 20 hours after first dose and patient-specific differences in peripheral non-tumor tissue (skin or plasma) paclitaxel levels 20 ± 4 hours after first dose.
- To determine if paclitaxel levels are higher at 20h after the 3rd dose than after the first dose, and if levels are higher at 20h after the 10th, 11th, or 12th dose than the 1st and 3rd dose.
- Compare pre-existing versus post-treatment antimitotic effects at 20h after the 1st dose, 20h after the 3rd dose, and 20h after the 10th, 11th, or 12th dose.
- Correlate drug levels and distribution with biomarkers including mitotic index, aneuploidy, chromosomal instability, and Ki67.
- Correlate pathologic response and clinical response with biomarkers including mitotic index, aneuploidy, CIN and Ki67.
- To test if CIN increases in patient tumors in response to paclitaxel and to evaluate the feasibility of these measurements by genomic analysis.
Initial Actual Primary and Study Completion Date registered as 8/16/2022 with 24 participants enrolled.
Per a Protocol Amendment dated 5/7/24, this study will re-open to enroll up to 50 participants. NCI funding and data sharing information added.
- Conditions
- Breast Neoplasm Female
- Being tested
- Paclitaxel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Also called Taxol
Paclitaxel is an FDA approved medication for treatment of curable breast cancer and is available by prescription at pharmacies throughout the United States.
| Study group | Role | What they receive |
|---|---|---|
| Weekly Paclitaxel | Experimental | Paclitaxel 80 mg/m2 will be initiated as standard infusion on days 1, 8, 15 of a 21-day cycle.
Participants will continue with paclitaxel 80 mg/m2 for cycles 2-4 prior to surgery. Receives: Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to Paclitaxel
To test if high cancers with high chromosomal instability (CIN) respond to paclitaxel better than low CIN cancers. Response determined by the percent decrease in linear measurement of tumor size on the greatest dimension per RECIST-like criteria
Measured: Up to 3 months
Secondary outcomes (9)
Tumor Level Difference of Paclitaxel
Identify patient-specific differences in tumor levels of paclitaxel at 20 hours after first dose.
This is measured by high-performance liquid chromatography of tumor and plasma samples and comparing variability between patients with descriptive statistics.
Measured: Up to 1 day
Non-Tumor Level Difference of Paclitaxel
Identify patient-specific differences in non-tumor (plasma) levels of paclitaxel at 20 hours after first dose.
This is measured by high-performance liquid chromatography of tumor and plasma samples and comparing variability between patients with descriptive statistics.
Measured: Up to 1 day
Paclitaxel Levels
Paclitaxel levels at the first dose, 20 hours after the 3rd dose, and 20 hours after the 12th dose. This is measured by high-performance liquid chromatography of tumor and plasma samples and comparing difference at two time points within the same patient with paired statistics.
Measured: Up to 79 days
Antimitotic Effects
Compare pre-existing versus post-treatment antimitotic effects at 20 hours after the 1st dose, 20 hours after the 3rd dose, and 20 hours after the 12th dose.
This is measured by tissue analysis of tumor samples with phospho-histone H3 and stains for spindle morphology to quantify mitotic index and mitotic characteristics at two time points using paired statistical analysis.
Measured: Up to 79 days
Mitotic Index
The mitotic index is a measure of cells arresting in mitosis, previously thought to be the major mechanism of taxol action. It is defined as the percentage of cells undergoing mitosis in a given population of cells. An elevated mitotic index indicates more cells are at this phase of the cell cycle at the time of sampling.
Measured: Baseline and 20 hours post-first dose
Correlate Drug Levels With Aneuploidy of Tumor
Correlate pathologic response and clinical response with biomarkers including aneuploidy
Measured: Up to 3 months
Correlate Drug Levels With Chromosomal Instability of Tumor
Correlate pathologic response and clinical response with biomarkers including CIN
Measured: Up to 3 months
Ki67 of Tumor
The Ki-67 protein is a cellular marker for proliferation. Ki-67 is an excellent marker to determine the growth fraction of a given cell population. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer.
Measured: Up to 3 months
Change in CIN Levels
There are many proposed ways to measure CIN. Here, we used # of multipolar spindles as a surrogate of CIN measures.
Measured: Baseline and 20 hours post-first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2017
- Study start13 Mar 2017
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
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 Breast Neoplasm FemaleStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Marina Sharifi, MD, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03096418
- Sponsor's protocol ID
- 2016-1489
- Other IDs
- NCI-2017-00338, UW16106, A534260, SMPH\MEDICINE\HEM-ONC, Protocol Version 10/10/2025, 1R01CA284747-01A1
- Status last verified
- Jun 2026
- First submitted
- 16 Mar 2017
- Last updated
- 16 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Scribano CM, Wan J, Esbona K, Tucker JB, Lasek A, Zhou AS, Zasadil LM, Molini R, Fitzgerald J, Lager AM, Laffin JJ, Correia-Staudt K, Wisinski KB, Tevaarwerk AJ, O'Regan R, McGregor SM, Fowler AM, Chappell RJ, Bugni TS, Burkard ME, Weaver BA. Chromosomal instability sensitizes patient breast tumors to multipolar divisions induced by paclitaxel. Sci Transl Med. 2021 Sep 8;13(610):eabd4811. doi: 10.1126/scitranslmed.abd4811. Epub 2021 Sep 8.
PubMed 34516829
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Weekly Paclitaxel and Biomarkers of Therapy Response
- ClinicalTrials.gov ID
- NCT03096418
- Acronym / sponsor ID
- 2016-1489
- Conditions
- Breast Neoplasm Female
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 13 Mar 2017 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 30 Mar 2017 (actual)
- Results
- Posted 13 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The hypothesis of this study is that paclitaxel levels increase chromosomal instability (CIN) in tumors and this is lethal to tumors that have pre-existing CIN. Treatment will be administered on an outpatient basis. Paclitaxel will be initiated as standard infusions on days 1, 8, and 15 of a 21-day cycle. Participants will continue with paclitaxel for cycles 2-4 prior to surgery.
Detailed description
Primary Objectives
- To test if cancers with high chromosomal instability (CIN) respond to paclitaxel better than low CIN cancers.
Secondary Objectives
- To identify patient-specific differences in tumor levels and distribution of paclitaxel at 20 hours after first dose and patient-specific differences in peripheral non-tumor tissue (skin or plasma) paclitaxel levels 20 ± 4 hours after first dose.
- To determine if paclitaxel levels are higher at 20h after the 3rd dose than after the first dose, and if levels are higher at 20h after the 10th, 11th, or 12th dose than the 1st and 3rd dose.
- Compare pre-existing versus post-treatment antimitotic effects at 20h after the 1st dose, 20h after the 3rd dose, and 20h after the 10th, 11th, or 12th dose.
- Correlate drug levels and distribution with biomarkers including mitotic index, aneuploidy, chromosomal instability, and Ki67.
- Correlate pathologic response and clinical response with biomarkers including mitotic index, aneuploidy, CIN and Ki67.
- To test if CIN increases in patient tumors in response to paclitaxel and to evaluate the feasibility of these measurements by genomic analysis.
Initial Actual Primary and Study Completion Date registered as 8/16/2022 with 24 participants enrolled.
Per a Protocol Amendment dated 5/7/24, this study will re-open to enroll up to 50 participants. NCI funding and data sharing information added.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Weekly Paclitaxel | Experimental | Drug: PaclitaxelPaclitaxel 80 mg/m2 will be initiated as standard infusion on days 1, 8, 15 of a 21-day cycle. Participants will continue with paclitaxel 80 mg/m2 for cycles 2-4 prior to surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Women with pathologically demonstrated breast cancer
- Patients must be candidates for neoadjuvant paclitaxel chemotherapy by their treating oncologist. No other investigational or commercial therapeutic agents may be given concurrently with the paclitaxel.
- Patients must not have metastatic disease on staging work-up per institutional guidelines.
- A formalin-fixed paraffin embedded tumor block (preferred) or unstained slides must be available from a prior biopsy of the primary tumor (preferred) or lymph node. A minimum of 8 slides must be available.
- The primary tumor or lymph node must be readily biopsied by surgery or radiology teams.
Key exclusion criteria (5 listed)
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel including to other drugs formulated in Cremophor(R) EL (polyoxyethylated castor oil).
- Patients with known HIV due to concern that chemotherapy may cause further immunosuppression and potential infectious complications.
- Patients on non-aspirin anti-coagulation (Coumadin, heparins, or clopidogrel) or with documented bleeding disorders will be excluded due to risk of bleeding with biopsy.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active severe infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, other malignancies requiring therapy or psychiatric illness/social situations that would limit compliance with study requirements as determined by treatment physician.
- Pregnant women are excluded from this study because paclitaxel is a pregnancy category D drug and may cause deleterious effects to the fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with paclitaxel, breastfeeding should be discontinued if the mother is enrolled in the trial.
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 |
|---|---|---|
| PaclitaxelAlso: TaxolPaclitaxel is an FDA approved medication for treatment of curable breast cancer and is available by prescription at pharmacies throughout the United States. | Drug | Weekly Paclitaxel |
Primary outcome
Response to Paclitaxel
Time frame: Up to 3 months
To test if high cancers with high chromosomal instability (CIN) respond to paclitaxel better than low CIN cancers. Response determined by the percent decrease in linear measurement of tumor size on the greatest dimension per RECIST-like criteria
9 secondary outcomes
Tumor Level Difference of Paclitaxel
Time frame: Up to 1 day
Non-Tumor Level Difference of Paclitaxel
Time frame: Up to 1 day
Paclitaxel Levels
Time frame: Up to 79 days
Antimitotic Effects
Time frame: Up to 79 days
Mitotic Index
Time frame: Baseline and 20 hours post-first dose
Correlate Drug Levels With Aneuploidy of Tumor
Time frame: Up to 3 months
Correlate Drug Levels With Chromosomal Instability of Tumor
Time frame: Up to 3 months
Ki67 of Tumor
Time frame: Up to 3 months
Change in CIN Levels
Time frame: Baseline and 20 hours post-first dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34516829Scribano CM, Wan J, Esbona K, Tucker JB, Lasek A, Zhou AS, Zasadil LM, Molini R, Fitzgerald J, Lager AM, Laffin JJ, Correia-Staudt K, Wisinski KB, Tevaarwerk AJ, O'Regan R, McGregor SM, Fowler AM, Chappell RJ, Bugni TS, Burkard ME, Weaver BA. Chromosomal instability sensitizes patient breast tumors to multipolar divisions induced by paclitaxel. Sci Transl Med. 2021 Sep 8;13(610):eabd4811. doi: 10.1126/scitranslmed.abd4811. Epub 2021 Sep 8.
- UW Carbone Cancer Center Home PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes
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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.
Marina Sharifi, MD, PhD principal investigator
University of Wisconsin, Madison
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Paclitaxel in people with Breast Neoplasm Female, run by University of Wisconsin, Madison at 2 sites 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 11 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 13 Oct 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?
Contact Cancer Connect (800-622-8922, clinicaltrials@cancer.wisc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response to Paclitaxel (time frame: Up to 3 months). 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 NCT03096418, 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 16 Jun 2026.