Clinical trial NCT03983538: Mathematical Modeling to Predict Response to Neoadjuvant Chemotherapy in Breast Cancer
Official title: A Single Center Pilot Study Evaluating the Use of Mathematical Modeling to Predict Response to Neoadjuvant Anthracycline / Taxane Based Chemotherapy in Women With HER2 Negative Stage II and III Breast Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Lead sponsor: New Mexico Cancer Research Alliance
Sponsor class: OTHER
First posted: 2019-06-12
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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

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.

Detailed description: This is a feasibility study evaluating the use of a mathematical model to predict response to standard neoadjuvant chemotherapy in patients with breast cancer. Chemotherapy will be protocol-approved chemotherapy regimen containing intravenous Doxorubicin (or Epirubicin), Cyclophosphamide, and Paclitaxel (or Docetaxel).

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

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.

Following the completion of neoadjuvant chemotherapy, surgical approach and adjuvant radiation and endocrine therapy are left to the discretion of the treating physicians.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Feasibility of using diagnostic needle core biopsy to mathematically predict ƒkill-path in women with breast cancer undergoing neoadjuvant chemotherapy
timeFrame: 5 years
measure: Feasibility of calculating tumor BVF from pre-chemotherapy gadolinium enhanced MRI of the breast in women with breast cancer undergoing neoadjuvant chemotherapy
timeFrame: 5 years
measure: 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
timeFrame: 5 years
Secondary outcomes:
measure: 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
timeFrame: 5 years
measure: Association between ƒkill-path and ƒkill-rad and biomarkers as calculated with a mathematical model
timeFrame: 5 years
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center
state: New Mexico
Study officials:
affiliation: University of New Mexico Cancer Center
name: Ursa Brown-Glaberman, MD
role: PRINCIPAL_INVESTIGATOR
References: