Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy

NCT03393741 | Terminated DMC FDA Drug

• 8 other identifiers: UW16151P30CA014520NCI-2017-016142017-0668A534260SMPH\MEDICINE\HEM-ONC1R01CA234904-01Protocol version: 1, 1/6/2017
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Eligible subjects will be assigned to study treatment arms by their treating oncologist, rather than by the study. The drug, dose, and schedule of administration will be determined by the treating physician per NCCN guidelines for standard of care chemotherapy regimens for recurrent or metastatic breast cancer. Study treatment arms include: Taxane (nab-paclitaxel or paclitaxel), Eribulin, Vinorelbine, Ixabepilone, or the control arm (non-microtubule targeted chemotherapies such as doxorubicin, carboplatin, or gemcitabine).

Conditions

Breast Cancer; Breast Neoplasms

Keywords

Metastatic breast cancer

Outcome Measures

Primary Outcomes (1)

• Feasibility of measuring biomarkers in advanced breast tumors at 20 +/- 2 hours after chemotherapy

  Advanced breast tumors safely sampled and analyzed from 35 subjects. In order to successfully test the hypothesis that chromosomal instability in part governs the effect of antimitotic therapies, advanced breast tumors samples must be collected, preserved, and analyzed at 20+/- 2 hours after chemotherapy in order to characterize the effect of the drug on the tumor. A primary question becomes is this process safe and feasible within these time constraints in our clinical setting.

  Up to 22 hours

Secondary Outcomes (9)

• Measure intratumoral drug levels at 20 +/- 2 hours after chemotherapy

  Up to 22 hours

• Measure serum drug levels at 20 +/- 2 hours after chemotherapy

  Up to 22 hours

• Measure PBMC pharmacodynamics at 20 +/- 2 hours after chemotherapy

  Up to 22 hours

• Assess effects of mitosis and DNA damage response at 20 +/- 2 hours after chemotherapy

  Up to 22 hours

• Correlate drug levels and cellular effects with response by RECIST 1:1 to chemotherapy

  Up to 2 months following completion of study treatment OR upon the systemic imaging following therapy completion (whichever is later)

Study Arms (5)

Taxane (nab-paclitaxel or paclitaxel)

Up to 10 participants will be enrolled on the Taxane arm. The dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed. Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression. Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.

Drug: Taxane; Drug: Chemotherapy

Eribulin

Up to 5 participants will be enrolled on the Eribulin arm. The dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed. Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression. Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.

Drug: Eribulin; Drug: Chemotherapy

Vinorelbine

Up to 5 participants will be enrolled on the Vinorelbine arm. TThe dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed. Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression. Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.

Drug: Vinorelbine; Drug: Chemotherapy

Ixabepilone

Up to 5 participants will be enrolled on the Ixabepilone arm. The dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed. Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression. Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.

Drug: Ixabepilone; Drug: Chemotherapy

Control Arm

Up to 10 participants will be enrolled on the control arm. The dose and schedule of administration is determined by the treating physician. The first dose will be coordinated in conjunction with research staff who will schedule a research biopsy to be completed on Day 2 of the first planned chemotherapy treatment cycle (C1D2). Participants are not eligible for replacement as long as they are able to have the C1D2 biopsy completed. Two tubes of blood of up to 15ml each drawn prior to chemotherapy and again just before or after research biopsy on C1D2. A 15ml sample of blood drawn at the time subject comes off study or at the time of disease progression. Tumor core biopsy is obtained as close as possible to 20 hours following initiation of the first planned treatment infusions. Between 2 and 4 cores will be obtained for research biopsy.

Drug: Chemotherapy

Interventions

Taxane DRUG

Taxane is a chemotherapeutic agent and a standard drug for treatment in breast cancer targeting microtubules. This drug is typically infused as a single agent for breast cancer therapy.

Also known as: paclitaxel, nab-paclitaxel, docetaxel

Taxane (nab-paclitaxel or paclitaxel)

Vinorelbine DRUG

Vinorelbine is a chemotherapeutic agent and a standard drug for treatment in breast cancer targeting microtubules. This drug is typically infused as a single agent for breast cancer therapy.

Also known as: vinca alkaloid

Vinorelbine

Ixabepilone DRUG

Ixabepilone is a chemotherapeutic agent and a standard drug for treatment in breast cancer targeting microtubules. This drug is typically infused as a single agent for breast cancer therapy.

Also known as: epothilone

Ixabepilone

Eribulin DRUG

Eribulin is a chemotherapeutic agent and a standard drug for treatment in breast cancer targeting microtubules. This drug is typically infused as a single agent for breast cancer therapy.

Also known as: halichondrins

Eribulin

Chemotherapy DRUG

Chemotherapy is used to treat various stages of breast cancer.

Control Arm; Eribulin; Ixabepilone; Taxane (nab-paclitaxel or paclitaxel); Vinorelbine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Men and women with metastatic or incurable breast cancer.

You may qualify if:

• Men and women with histologically or cytologically demonstrated breast cancer that is deemed metastatic or incurable by the treating physician.
• It is medically appropriate to treat the patient with an antimitotic agent or an intravenous control chemotherapeutic agent by IV infusion at standard doses as per the treating physician. Please see NCCN guidelines for standard of care, p58 for standard chemotherapy regimens for recurrent or metastatic breast cancer7.
• The patient has measureable disease as determined by RECIST 1.1.
• Archived tissue is available from either primary, metastatic site or both.
• It is safe and feasible to obtain a research tumor biopsy on cycle 1 day 2 with a biopsy of an accessible lesion such as liver, lung, lymph node, skin, breast, or bone.
• All pre-chemotherapy test results (tests per treating oncologist discretion) have been reviewed and deemed appropriate for planned chemotherapy by the patient's treating oncologist.

You may not qualify if:

• HER2+ breast cancer by standard criteria.
• Pregnant women are excluded from this study because systemic chemotherapy 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 systemic chemotherapy, breastfeeding should be discontinued if the mother is enrolled in the trial.
• Planned treatment with hormonal therapy, or targeted oral therapy during trial enrollment.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Zhou AS, Tucker JB, Scribano CM, Lynch AR, Carlsen CL, Pop-Vicas ST, Pattaswamy SM, Burkard ME, Weaver BA. Diverse microtubule-targeted anticancer agents kill cells by inducing chromosome missegregation on multipolar spindles. PLoS Biol. 2023 Oct 26;21(10):e3002339. doi: 10.1371/journal.pbio.3002339. eCollection 2023 Oct.

  PMID: 37883329 DERIVED

Related Links

• UW Carbone Cancer Center home page

Biospecimen

Retention: SAMPLES WITH DNA

Tissue samples, pre- and post- 20 hr (+/- 2 hrs) chemotherapy Blood samples, pre- and post- 20 hr (+/- 2 hrs) chemotherapy

MeSH Terms

Conditions

Breast Neoplasms

Interventions

taxane; Paclitaxel; 130-nm albumin-bound paclitaxel; Docetaxel; Vinorelbine; Vinca Alkaloids; ixabepilone; Epothilones; eribulin; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Macrolides; Polyketides; Lactones; Therapeutics

Study Officials

• Mark Burkard, MD, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2017
• First Posted: January 8, 2018
• Study Start: January 29, 2018
• Primary Completion: February 11, 2024
• Study Completion: February 11, 2024
• Last Updated: June 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)