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

NCT ID: NCT03393741

Last Updated: 2024-06-25

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 5 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-01-29
• Study Completion Date: 2024-02-11

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).

Detailed Description

During the screening visit, the following will be taken: medical history; physical exam; ECOG performance status; a pregnancy test if indicated per physician (confirmation of the clinical testing result or assessment of the treating physician whether or not the subject is capable of pregnancy); AST, ALT, CBC (per oncologist); 15 mL blood sample for drug level assessment; 15 mL blood sample for circulating tumor DNA (ctDNA); follow up assessments of cancer; RECIST 1.1 response measurements; and an archived FFPE sample (8 slides) will be obtained.

While enrolled on study, subjects will have the following procedures:

• 15 mL blood sample for drug level assessment on C1D2
• 15 mL blood sample for circulating tumor DNA (ctDNA) on C1D2 and at progression or end of study for a total of 30 mL
• Adverse events related to study procedures (research biopsy & blood draws) will be assessed on C1D2 and at progression or end of study
• Toxicity evaluations will occur throughout the study per the treating MD
• Follow-up assessments of cancer will occur throughout the study per the treating MD
• RECIST 1.1 response measurements will be taken at standard of care imaging
• Fresh biopsy or tumor sampling (4 cores) for analysis of intratumoral drug levels and biomarkers including: markers of proliferation (mitotic index), aneuploidy, and sequencing analysis (ctDNA) on C1D2.

The tests being performed on the samples as part of this study are not investigational.

Subjects will be followed with imaging scans and tumor markers as deemed appropriate by the treating physician. Follow-up scans will be recommended every ~3 cycles as per standard of care. Subjects will be followed for the duration of treatment initiated while taking part in this study. Follow-up will discontinue either 2 months following completion of planned breast cancer treatment or upon the systemic imaging following therapy completion (whichever is later).

Conditions

Breast Cancer; Breast Neoplasms

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Taxane

Intervention Type: 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.

Chemotherapy

Intervention Type: DRUG

Chemotherapy is used to treat various stages of breast cancer.

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.

Eribulin

Intervention Type: 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.

Chemotherapy

Intervention Type: DRUG

Chemotherapy is used to treat various stages of breast cancer.

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.

Vinorelbine

Intervention Type: 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.

Chemotherapy

Intervention Type: DRUG

Chemotherapy is used to treat various stages of breast cancer.

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.

Ixabepilone

Intervention Type: 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.

Chemotherapy

Intervention Type: DRUG

Chemotherapy is used to treat various stages of breast cancer.

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.

Chemotherapy

Intervention Type: DRUG

Chemotherapy is used to treat various stages of breast cancer.

Interventions

Taxane

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.

Intervention Type: DRUG

Vinorelbine

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.

Intervention Type: DRUG

Ixabepilone

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.

Intervention Type: DRUG

Eribulin

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.

Intervention Type: DRUG

Chemotherapy

Chemotherapy is used to treat various stages of breast cancer.

Intervention Type: DRUG

Other Intervention Names

paclitaxel; nab-paclitaxel; docetaxel; vinca alkaloid; epothilone; halichondrins

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Burkard, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37883329 (View on PubMed)

Related Links

http://www.uwhealth.org/cancer

UW Carbone Cancer Center home page

Other Identifiers

P30CA014520

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2017-01614

Identifier Type: REGISTRY

Identifier Source: secondary_id

2017-0668

Identifier Type: OTHER

Identifier Source: secondary_id

A534260

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH\MEDICINE\HEM-ONC

Identifier Type: OTHER

Identifier Source: secondary_id

1R01CA234904-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Protocol version: 1, 1/6/2017

Identifier Type: OTHER

Identifier Source: secondary_id

UW16151

Identifier Type: -

Identifier Source: org_study_id