RESPONSE: Correlation of Clinical Response to Pathologic Response in Patients With Early Breast Cancer

Sponsor

Baylor Breast Care Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05020860

Collaborator

(none)

185

Enrollment

Locations

Arms

66.6

Anticipated Duration (Months)

92.5

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to learn whether clinical response (the amount a tumor shrinks based on imaging or tumor measurements obtained by physical exam) predicts pathologic response (the amount of tumor remaining when surgery is performed) in patients with breast cancer who are receiving chemotherapy prior to surgery.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Breast Neoplasm Breast Cancer Female Breast Cancer Invasive Breast Cancer Stage II Breast Cancer Stage III Triple Negative Breast Cancer Hormone Receptor-positive Breast Cancer HER2-positive Breast Cancer Triple Negative Breast Neoplasms Estrogen Receptor-positive Breast Cancer	Drug: Paclitaxel Drug: Carboplatin Drug: Trastuzumab Drug: Pertuzumab Drug: Doxorubicin Drug: Cyclophosphamide	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

185 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial to Correlate Early Clinical Response to Pathologic Outcome With Neoadjuvant Systemic Therapy in Patients With Early Stage Breast Cancer

Anticipated Study Start Date :

Jun 15, 2022

Anticipated Primary Completion Date :

Oct 15, 2025

Anticipated Study Completion Date :

Jan 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Triple Negative Breast Cancer (for tumors > 5 cm) Paclitaxel IV plus Carboplatin IV (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (4 cycles total)	Drug: Paclitaxel 80 mg/m2 IV administered on days 1, 8, 15 of each 21-day cycle Other Names: Taxol Drug: Carboplatin Carboplatin AUC 1.5 IV administered on days 1, 8, 15 of each 21-day cycle Drug: Doxorubicin 60 mg/m2 IV administered on day 1 of each 14-day cycle Other Names: Adriamycin Drug: Cyclophosphamide 600 mg/m2 IV administered on day 1 of each 14-day cycle Other Names: Cytoxan
Active Comparator: Triple Negative Breast Cancer (for tumors < 5 cm) Paclitaxel IV (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (4 cycles total)	Drug: Paclitaxel 80 mg/m2 IV administered on days 1, 8, 15 of each 21-day cycle Other Names: Taxol Drug: Doxorubicin 60 mg/m2 IV administered on day 1 of each 14-day cycle Other Names: Adriamycin Drug: Cyclophosphamide 600 mg/m2 IV administered on day 1 of each 14-day cycle Other Names: Cytoxan
Active Comparator: HER2-Positive Breast Cancer Paclitaxel IV plus Trastuzumab IV plus Pertuzumab IV (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV administered (4 cycles total)	Drug: Paclitaxel 80 mg/m2 IV administered on days 1, 8, 15 of each 21-day cycle Other Names: Taxol Drug: Trastuzumab Trastuzumab 8 mg/kg loading dose, followed by 6 mg/kg maintenance dose, administered on day 1 of each 21-day cycle Other Names: Herceptin Drug: Pertuzumab Pertuzumab 840 mg loading dose, followed by 420 mg maintenance dose, administered on day 1 of each 21-day cycle Other Names: Perjeta Drug: Doxorubicin 60 mg/m2 IV administered on day 1 of each 14-day cycle Other Names: Adriamycin Drug: Cyclophosphamide 600 mg/m2 IV administered on day 1 of each 14-day cycle Other Names: Cytoxan
Active Comparator: Hormone Receptor Positive Breast Cancer Paclitaxel IV plus Carboplatin IV (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (4 cycles total)	Drug: Paclitaxel 80 mg/m2 IV administered on days 1, 8, 15 of each 21-day cycle Other Names: Taxol Drug: Doxorubicin 60 mg/m2 IV administered on day 1 of each 14-day cycle Other Names: Adriamycin Drug: Cyclophosphamide 600 mg/m2 IV administered on day 1 of each 14-day cycle Other Names: Cytoxan

Outcome Measures

Primary Outcome Measures

Change in Clinical Tumor Measurement vs. Pathologic Response [Baseline and at surgery (after 20 weeks)]
Clinical tumor measurements are tumor measurements obtain via imaging (mammogram or ultrasound) or by physical exam. Pathologic response is the amount of tumor remaining at the time of surgery, as determined by the pathologist.

Secondary Outcome Measures

Pathologic Complete Response Rate in each Breast Cancer Subtype [20 weeks]
A pathologic complete response (pCR) means that there is no residual invasive cancer identified in the tissue removed at surgery. The frequency of pCR will be estimated for each breast cancer subtype (triple negative, hormone receptor positive, and HER2-positive)
Predictive value of clinical response following 1 cycle of chemotherapy to predict pathologic complete response [20 weeks]
This aims to determine whether a 30 percent reduction in tumor size (as measured by physical exam or imaging) following one cycle of chemotherapy can predict whether a patient will have no residual invasive cancer at the time of surgery

Other Outcome Measures

Change in circulating tumor DNA (ctDNA) levels from baseline to surgery [20 weeks]
ctDNA is DNA from a tumor circulating in a patient's bloodstream. The goal of this is to determine whether a decrease in ctDNA levels (as measured from baseline to surgery) correlates to clinical and/or pathologic response

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must be at least 18 years old, and legally able to provide informed consent. Both men and women are eligible.
Participants must have histologically confirmed, invasive breast cancer. Tumor may be triple negative (as defined by ASCO-CAP guidelines), HER2-positive (as defined by ASCO-CAP guidelines), or high-risk estrogen receptor positive (as defined by ASCO-CAP guidelines). High risk is defined as a tumor that meets at least two of the following criteria: 1) histologic grade 3; 2) patient age less than 50 years; 3) Estrogen Receptor (ER) < 6/ or 4) ki-67 ≥ 30%.
Tumors must be at least 2 cm by clinical exam (palpation or ultrasound).
Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Participants must have a left ventricular ejection fraction ≥ the institutional lower limit of normal, as assessed by echocardiogram or Multigated Acquisition (MUGA )scan.
Participants must have adequate organ function, as determined by the following parameters:
Absolute Neutrophil Count (ANC) ≥ 1200/mm3
Platelets ≥ 100,000/mm3
Hemoglobin ≥ 10 g/dL
Total bilirubin ≤ institutional upper limit of normal (ULN), unless the patient has Gilbert's disease or similar syndrome
Alkaline phosphatase (ALP) ≤ 2.5 x institutional ULN
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN
Serum creatinine ≤ institutional ULN
The patient, if of childbearing potential, is willing to use effective, non-hormonal contraception while on treatment.
Participation in a concurrent clinical trial is permitted, with principal investigator approval.

Exclusion Criteria:

Participants must not have definitive clinical or radiologic evidence of Stage IV disease
Participants must not have bilateral invasive breast cancer
Participants must not have inflammatory breast cancer
Patients must not be pregnant or lactating
Participants must not have a history of an excisional biopsy or lumpectomy performed prior to study entry
Participants must not have previously received treatment with anthracyclines for any malignancy.
Participants must not have received any treatment for currently diagnosed breast cancer prior to enrollment - including endocrine therapy, chemotherapy, targeted therapy, or radiation.
Participants must not have a history of cardiac disease that would preclude the use of drugs included in these treatment regimens. This includes, but is not limited to:
Angina pectoris requiring the use of anti-anginal medication
Ventricular arrhythmias except for benign premature ventricular contractions
Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
Conduction abnormality requiring a pacemaker
Valvular disease with documented compromise in cardiac function;
Symptomatic pericarditis
Documented cardiomyopathy
History of documented congestive heart failure
Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities, on assessment of left ventricular function.
Participants must not have HIV, hepatitis B, or hepatitis C infections.
Participants must not have a history of non-breast malignancies (with the exception of in situ cancers treated only by local excision, and basal cell or squamous cell carcinoma of the skin) within 5 years prior to enrollment.
Participants must not have any other non-malignant systemic disease that would preclude treatment with any of the treatment regimens or prevent required follow-up.
Participants must not have any psychiatric or addictive disorders, adverse social situations, or other medical conditions that, in the opinion of the investigator, would preclude the patient from meeting study requirements.