Neoadjuvant Weekly Paclitaxel and Biomarkers of Therapy Response

Sponsor
University of Wisconsin, Madison (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03096418
Collaborator
(none)
24
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Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
N/A

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
N/A
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 :
Mar 13, 2017
Anticipated Primary Completion Date :
Jul 1, 2022
Anticipated Study Completion Date :
Jul 1, 2022

Arms and Interventions

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 Names:
  • Taxol
  • Outcome Measures

    Primary Outcome Measures

    1. Response to paclitaxel [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

    Secondary Outcome Measures

    1. Tumor Level Difference of Paclitaxel [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. Non-Tumor Level Difference of Paclitaxel [Up to 1 day]

      Identify patient-specific differences in non-tumor (skin or 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.

    3. Tumor Level Tissue Distribution of Paclitaxel [Up to 1 day]

      Identify patient-specific tissue distribution in tumor levels of paclitaxel at 20 hours after first dose. This is measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to compare variability in distribution patterns between patients with descriptive statistics.

    4. Non-Tumor Level Tissue Distribution of Paclitaxel [Up to 1 day]

      Identify patient-specific tissue distribution in non-tumor (skin or plasma) levels of paclitaxel at 20 hours after first dose. This is measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to compare variability in distribution patterns between patients with descriptive statistics.

    5. Paclitaxel Levels [Up to 79 days]

      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.

    6. Antimitotic effects [Up to 79 days]

      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.

    7. Correlate drug levels with mitotic index [Up to 3 months]

      Correlate pathologic response and clinical response with biomarkers including mitotic index

    8. Correlate drug levels with aneuploidy of tumor [Up to 3 months]

      Correlate pathologic response and clinical response with biomarkers including aneuploidy

    9. Correlate drug levels with chromosomal instability of tumor [Up to 3 months]

      Correlate pathologic response and clinical response with biomarkers including CIN

    10. Correlate drug levels with Ki67 of tumor [Up to 3 months]

      Correlate pathologic response and clinical response with biomarkers including Ki67.

    11. Correlate drug levels and biomarkers [Up to 3 months]

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

    12. Pathologic response and clinical response to mitotic index of tumor [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.

    13. Pathologic response and clinical response to aneuploidy of tumor [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.

    14. Pathologic response and clinical response to chromosomal instability of tumor [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.

    15. Pathologic response and clinical response to Ki67 of tumor [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.

    16. Pathologic and clinical responses and biomarkers [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.

    17. Change in CIN levels [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Wisconsin Carbone Cancer Center Madison Wisconsin United States 53792

    Sponsors and Collaborators

    • University of Wisconsin, Madison

    Investigators

    • Principal Investigator: Mark Burkard, University of Wisconsin, Madison

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    University of Wisconsin, Madison
    ClinicalTrials.gov Identifier:
    NCT03096418
    Other Study ID Numbers:
    • UW16106
    • NCI-2017-00338
    • 2016-1489
    • A534260
    • SMPH\MEDICINE\HEM-ONC
    • Protocol Version 8/23/2019
    First Posted:
    Mar 30, 2017
    Last Update Posted:
    Apr 18, 2022
    Last Verified:
    Apr 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 18, 2022