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Neoadjuvant Weekly Paclitaxel and Biomarkers of Therapy Response

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ClinicalTrials.gov Identifier: NCT03096418
Recruitment Status : Recruiting
First Posted : March 30, 2017
Last Update Posted : September 26, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief 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 1-day cycle. Participants will continue with paclitaxel for cycles 2-4 prior to surgery.


Condition or disease Intervention/treatment Phase
Breast Neoplasm Female Drug: Paclitaxel Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Weekly Paclitaxel and Biomarkers of Therapy Response
Actual Study Start Date : March 13, 2017
Estimated Primary Completion Date : September 15, 2020
Estimated Study Completion Date : October 15, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel

Arm Intervention/treatment
Experimental: Weekly Paclitaxel

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.

Drug: Paclitaxel
Paclitaxel is an FDA approved medication for treatment of curable breast cancer and is available by prescription at pharmacies throughout the United States.
Other Name: Taxol




Primary Outcome Measures :
  1. Response to paclitaxel [ Time Frame: Up to 3 months ]

    To test is 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



Secondary Outcome Measures :
  1. Tumor level difference [ Time Frame: Up to 1 day ]

    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.


  2. Paclitaxel levels at 3rd dose [ Time Frame: Up to 16 days ]

    Determine if paclitaxel levels are higher at 20 hours after the 3rd dose than after the first 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.


  3. Antimitotic effects [ Time Frame: Up to 16 days ]

    Compare pre-existing versus post-treatment antimitotic effects at 20 hours after the 1st dose and 2 hours after the 3rd 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.


  4. Correlate drug levels with mitotic index [ Time Frame: Up to 3 months ]
    Correlate pathologic response and clinical response with biomarkers including mitotic index

  5. Correlate drug levels with aneuploidy of tumor [ Time Frame: Up to 3 months ]
    Correlate pathologic response and clinical response with biomarkers including aneuploidy

  6. Correlate drug levels with chromosomal instability of tumor [ Time Frame: Up to 3 months ]
    Correlate pathologic response and clinical response with biomarkers including CIN

  7. Correlate drug levels with Ki67 of tumor [ Time Frame: Up to 3 months ]
    Correlate pathologic response and clinical response with biomarkers including Ki67.

  8. Correlate drug levels and biomarkers [ Time Frame: Up to 3 months ]
    Correlate pathologic response and clinical response with other biomarkers of tumor.

  9. Pathologic response and clinical response to mitotic index of tumor [ Time Frame: Up to 3 months ]

    Correlate pathologic response and clinical response with biomarkers including mitotic index.

    These correlations will be considered preliminary and results will be interpreted in the context of other studies being performed in metastatic breast cancer.


  10. Pathologic response and clinical response to aneuploidy of tumor [ Time Frame: Up to 3 months ]

    Correlate pathologic response and clinical response with biomarkers including aneuploidy.

    These correlations will be considered preliminary and results will be interpreted in the context of other studies being performed in metastatic breast cancer.


  11. Pathologic response and clinical response to chromosomal instability of tumor [ Time Frame: Up to 3 months ]

    Correlate pathologic response and clinical response with biomarkers including CIN.

    These correlations will be considered preliminary and results will be interpreted in the context of other studies being performed in metastatic breast cancer.


  12. Pathologic response and clinical response to Ki67 of tumor [ Time Frame: Up to 3 months ]

    Correlate pathologic response and clinical response with biomarkers including Ki67.

    These correlations will be considered preliminary and results will be interpreted in the context of other studies being performed in metastatic breast cancer.


  13. Pathologic and clinical responses and biomarkers [ Time Frame: Up to 3 months ]

    Correlate pathologic response and clinical response with other biomarkers of tumor.

    These correlations will be considered preliminary and results will be interpreted in the context of other studies being performed in metastatic breast cancer.


  14. Change in CIN levels [ Time Frame: Up to 3 months ]

    Test if CIN increases in patient tumors in response to paclitaxel and to evaluate the feasibility of these measurements by genomic analysis.

    Multiple genomic analyses have been proposed to measure CIN and aneuploidy in tumors. These include whole genome sequencing with high depth, SNP-array analysis, Comparative Genomic Hybridization and others. However, this is rapidly changing field with new technologies and analytic methods emerging weekly. We anticipate performing high-depth whole genome sequencing from three independent core samples per biopsy as a pilot analysis. Based on our experience with initial samples, and on available technologies and analytic methods available at the time of analysis, we may select another genomic sequencing and/or hybridization methods to optimally determine the changes in CIN. Fluorescence-in-situ hybridization will be used as a companion method.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 with CBC and liver function studies.
  • A formalin-fixed paraffin embedded tumor block (preferred) or unstained slides must be available from a prior biopsy of the primary tumor 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.
  • 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 UWCCC policy definition) must agree to use effective contraception as discussed with treating oncologist for the duration of the study.

Exclusion Criteria:

  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03096418


Contacts
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Contact: Cancer Connect 800-622-8922 skotila@wisc.edu

Locations
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United States, Wisconsin
University of Wisconsin Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53792
Contact: Cancer Connect    800-622-8922    skotila@wisc.edu   
Principal Investigator: Mark Burkard         
Sponsors and Collaborators
University of Wisconsin, Madison
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Mark Burkard University of Wisconsin, Madison

Additional Information:
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Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT03096418     History of Changes
Other Study ID Numbers: UW16106
P30CA014520 ( U.S. NIH Grant/Contract )
NCI-2017-00338 ( Registry Identifier: NCI CTRP )
2016-1489 ( Other Identifier: Institutional Review Board )
A534260 ( Other Identifier: UW Madison )
SMPH/MEDICINE/MEDICINE*H ( Other Identifier: UW Madison )
First Posted: March 30, 2017    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action