Mathematical Modeling to Predict Response to Neoadjuvant Chemotherapy in Breast Cancer

NCT03983538 | Completed

• 1 other identifier: INST 1411
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a feasibility study evaluating the use of a mathematical model to predict response to standard neoadjuvant anthracycline / taxane based chemotherapy in patients with breast cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Feasibility of using diagnostic needle core biopsy to mathematically predict ƒkill-path in women with breast cancer undergoing neoadjuvant chemotherapy

  To assess the feasibility of using diagnostic needle core biopsy to mathematically predict ƒkill-path (fraction of tumor cells killed calculated using data obtained from histopathology) in 10 women with stage II-III Her2-negative, Estrogen Receptor (ER) positive or negative infiltrating ductal carcinoma (IDC) of the breast undergoing neoadjuvant anthracycline / taxane based chemotherapy. Calculation of patient specific distribution of liver portal radii or characteristic vessel radius (rb), BVF, and the distance that drugs diffuse through tumor tissue (L) and ƒkill-path (using the investigators' mathematical model) will be obtained via analysis of pre-chemotherapy hematoxylin and eosin (H and E) stained section of diagnostic needle core biopsy specimen. Feasibility of the primary objective will be claimed if the necessary minimum samples are collected to calculate these parameters in 60% of patients.

  5 years

• Feasibility of calculating tumor BVF from pre-chemotherapy gadolinium enhanced MRI of the breast in women with breast cancer undergoing neoadjuvant chemotherapy

  To assess the feasibility of calculating patient specific fraction of blood volume within the tumor (tumor BVF) using data obtained from radiographic imaging (ƒkill-rad) from pre-chemotherapy gadolinium enhanced magnetic resonance imaging (MRI) of the breast in 10 women with stage II-III Her2-negative, ER positive or negative infiltrating ductal carcinoma (IDC) of the breast undergoing neoadjuvant anthracycline / taxane based chemotherapy. Calculation of patient specific BVF (using the investigators' mathematical model) will be obtained via analysis of pre-chemotherapy gadolinium enhanced MRI of the breast. Feasibility of the secondary objective will be claimed if the necessary minimum samples are collected to calculate these parameters in 60% of patients.

  5 years

• Feasibility of calculating ƒkill-rad from pre-chemotherapy gadolinium enhanced MRI of the breast in women with breast cancer undergoing neoadjuvant anthracycline / taxane based chemotherapy

  To assess the feasibility of calculating patient specific fraction of tumor cells killed using data obtained from radiographic imaging (ƒkill-rad) from pre-chemotherapy gadolinium enhanced magnetic resonance imaging (MRI) of the breast in 10 women with stage II-III Her2-negative, ER positive or negative infiltrating ductal carcinoma (IDC) of the breast undergoing neoadjuvant anthracycline / taxane based chemotherapy. Calculation of patient specific ƒkill-rad (using the investigators' mathematical model) will be obtained via analysis of pre-chemotherapy gadolinium enhanced MRI of the breast. Feasibility of the secondary objective will be claimed if the necessary minimum samples are collected to calculate these parameters in 60% of patients.

  5 years

Secondary Outcomes (2)

• Association between ƒkill-path and ƒkill-rad as calculated with the investigator's mathematical model and response to neoadjuvant chemotherapy at the time of surgery

  5 years

• Association between ƒkill-path and ƒkill-rad and biomarkers as calculated with a mathematical model

  5 years

Study Arms (1)

Patients receiving chemotherapy

Patients receive a protocol-approved chemotherapy regimen containing Doxorubicin (or Epirubicin), Cyclophosphamide, and Paclitaxel (or Docetaxel) based on the patient and/or physician preference.

Other: Mathematical modeling to predict response to chemotherapy

Interventions

Mathematical modeling to predict response to chemotherapy OTHER

Mathematical modeling using the patient's diagnostic core biopsy and baseline MRI of the breast will be used to predict the response to above therapy.

Patients receiving chemotherapy

Eligibility Criteria

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

Study Population

Women with Stage II-III HER2 negative breast cancer who are candidates for neoadjuvant anthracycline / taxane based chemotherapy

You may qualify if:

• Women with newly diagnosed human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor (ER) positive or negative, progesterone receptor (PR) positive or negative infiltrating ductal carcinoma (IDC) of the breast
• Clinically stage II-III
• Patients with inflammatory, multifocal, multicentric and synchronous bilateral breast cancers are allowed. However, in patients with inflammatory breast cancer, patients must have a measurable, biopsied mass within the breast pre-chemotherapy.
• Willing and able to provide informed consent
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1
• Patients must be able to receive neoadjuvant anthracycline / taxane based chemotherapy in the opinion of the treating physician. Criteria include:
• Adequate bone marrow function, as defined by peripheral granulocyte count of ≥ 1,500/mm3, and platelet count ≥100,000/mm3
• Adequate renal function with creatinine levels ≤ 1.5 X the upper limit of normal and estimated glomerular filtration rate (eGFR) \>30.
• Adequate liver function with a bilirubin, Alkaline phosphatase and transaminases (ALT and AST) of ≤ 1.5 X the institutional upper limit of normal.
• Multigated acquisition (MUGA) or echocardiogram (ECHO) demonstrating a left ventricular ejection fraction (LVEF) within institutional normal limits
• Women of reproductive potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Patients may also co-enroll in trials that compare local therapies, or compare systemic adjuvant therapies.
• Patients must have had (or be scheduled to have) a pre neoadjuvant chemotherapy MRI of the breast with gadolinium contrast as part of their planned routine breast cancer care.

You may not qualify if:

• Patients must not have had surgery or radiation or begun chemotherapy or endocrine therapy for their breast cancer prior to registration.
• Patients must not be pregnant or nursing due to the possibility of harm to a fetus or nursing infant from this treatment regimen.
• Presence of electrically, magnetically, or mechanically activated implants including cardiac pacemakers, cochlear implants, magnetic surgical clips or prosthesis that would preclude MRI.
• History of severe claustrophobia
• History of allergic reaction to gadolinium
• Patients must not have metastatic disease
• Baseline sensory/motor neuropathy \> grade 2
• Clinically significant cardiovascular disease
• Serious intercurrent infection or nonmalignant medical illness
• Creatinine clearance prohibiting the use of gadolinium (eGFR \< 30)

Sponsors & Collaborators

• New Mexico Cancer Research Alliance: lead

Study Sites (1)

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Ursa Brown-Glaberman, MD

  University of New Mexico Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: June 12, 2019
• Study Start: June 2, 2015
• Primary Completion: January 28, 2018
• Study Completion: January 28, 2018
• Last Updated: May 12, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)