Molecular Triaging of Newly Diagnosed Breast Cancer for Preoperative Therapies
Trial Snapshot
- Phase
- Not Applicable
- Status
- Withdrawn
- Sponsor
- M.D. Anderson Cancer Center
- Primary Endpoint
- Pathological Response Rate in Patients
Study Overview
Brief Summary
The goal of this clinical research study is to learn if using "gene signatures" can be an effective way to decide the best treatment for breast cancer patients. Gene signatures may be able to help researchers predict who will respond to chemotherapy given before surgery.
Detailed Description
At this time, treatment of stage I-III breast cancer for patients who are at high risk for the cancer returning is surgery and chemotherapy. If the cancer is positive for estrogen hormone receptor, patients also have endocrine therapy.
The most common standard chemotherapy treatment regimens for breast cancer at M. D. Anderson are paclitaxel (T), followed by treatments with fluorouracil (F), doxorubicin (A) or epirubicin (E), and cyclophosphamide (C). These chemotherapy combinations are known as T/FAC and T/FEC. However, not all patients respond to these treatments, so researchers at M. D. Anderson have developed tests to predict how much a person's breast cancer might respond to T/FAC or T/FEC chemotherapy.
Fine needle aspiration (FNA) of the tumor are collected after numbing the skin of the breast with local anesthesia, and the genes within the FNA sample are measured to calculate the results of treatment prediction tests before treatment is selected.
In this research study, the gene-based tests will help to select treatment based on the predictions of response to chemotherapy, and to then measure the tumor response from the surgery after the treatment.
Study Drugs:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients 18 years of age or older with histologically confirmed HER2-normal (defined as fluorescence in situ hybridization, FISH < 2.2 or immunohistochemistry, IHC <3+ if FISH result is not available) invasive carcinoma of the breast for whom systemic adjuvant therapy is clinically indicated.
- •Patients must have intact cancer in the breast and intact regional lymph nodes (diagnostic core needle or fine needle biopsies are allowed).
- •Routine estrogen, progesterone and HER-2 receptor determination must be performed before starting therapy.
- •Patients with prior history of breast cancer are eligible.
- •Patients with bilateral breast cancers are eligible.
- •Women of childbearing potential must have a negative serum pregnancy test within 2 weeks of starting chemotherapy. Patients must agree to barrier contraception (condom) while on study.
- •Patients must agree to undergo pretreatment needle biopsy of the primary tumor in the breast for molecular profiling.
- •Patients must agree to undergo surgery at MDACC and if assigned to bevacizumab containing chemotherapy it must be administered at MDACC.
Exclusion Criteria
- •Patients for whom anthracycline or paclitaxel chemotherapies are contraindicated, including: uncompensated congestive heart failure, myocardial infarction within the past 12 months, pre-existing peripheral neuropathy > grade 2, prior doxorubicin therapy with > cumulative dose of 240 mg/m^2
- •Women who had lumpectomy or surgical partial excisional biopsy of the cancer, or sentinel lymph node biopsy of a positive node, before starting preoperative therapy.
- •Exclusion criteria for bevacizumab therapy; inadequately controlled hypertension (defined as systolic blood pressure >/= 140 mmHg and/or diastolic blood pressure >/= 90 mmHg).
- •Exclusion criteria for bevacizumab therapy, prior history of hypertensive crisis or hypertensive encephalopathy, stroke or transient ischemic attacks.
- •Exclusion criteria for bevacizumab therapy, history of myocardial infarction, unstable angina or congestive heart failure within 12 months prior to starting therapy.
- •Exclusion criteria for bevacizumab therapy, aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis within 6 months prior to starting therapy.
- •Exclusion criteria for bevacizumab therapy, history of hemoptysis ( 1/2 teaspoon of bright red blood per episode) within 1 month prior to starting therapy or evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
- •Exclusion criteria for bevacizumab therapy. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting therapy or core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to starting therapy.
- •Exclusion criteria for bevacizumab therapy, history of abdominal fistula or gastrointestinal perforation within 6 months prior to starting therapy.
- •Exclusion criteria for bevacizumab therapy, serious, non-healing wound or fracture or active ulcer.
- •Proteinuria within 1 months of starting therapy as demonstrated by either (a) Urine protein:creatinine (UPC) ratio >/= 1.0 or (b) proteinuria >/= 2+ by urine dipstick test. Patients discovered to have >/=2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate </= 1g of protein in 24 hours to be eligible.
Arms & Interventions
Group 1: ER-Positive
Participants with Estrogen Receptor (ER)-Positive breast cancers receive Standard T/FAC or T/FEC chemotherapy before surgery.
T/FAC or T/FEC: Combination chemotherapy with sequential paclitaxel (80 mg/m2) weekly x 12 weeks followed by 5-fluorouracil (500 mg/m2), cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) or epirubicin (100 mg/m2) (FAC or FEC) once every 3 weeks for 4 treatments.
Intervention: Paclitaxel (Drug)
Group 1: ER-Positive
Participants with Estrogen Receptor (ER)-Positive breast cancers receive Standard T/FAC or T/FEC chemotherapy before surgery.
T/FAC or T/FEC: Combination chemotherapy with sequential paclitaxel (80 mg/m2) weekly x 12 weeks followed by 5-fluorouracil (500 mg/m2), cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) or epirubicin (100 mg/m2) (FAC or FEC) once every 3 weeks for 4 treatments.
Intervention: Fluorouracil (Drug)
Group 1: ER-Positive
Participants with Estrogen Receptor (ER)-Positive breast cancers receive Standard T/FAC or T/FEC chemotherapy before surgery.
T/FAC or T/FEC: Combination chemotherapy with sequential paclitaxel (80 mg/m2) weekly x 12 weeks followed by 5-fluorouracil (500 mg/m2), cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) or epirubicin (100 mg/m2) (FAC or FEC) once every 3 weeks for 4 treatments.
Intervention: Doxorubicin (Drug)
Group 1: ER-Positive
Participants with Estrogen Receptor (ER)-Positive breast cancers receive Standard T/FAC or T/FEC chemotherapy before surgery.
T/FAC or T/FEC: Combination chemotherapy with sequential paclitaxel (80 mg/m2) weekly x 12 weeks followed by 5-fluorouracil (500 mg/m2), cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) or epirubicin (100 mg/m2) (FAC or FEC) once every 3 weeks for 4 treatments.
Intervention: Epirubicin (Drug)
Group 1: ER-Positive
Participants with Estrogen Receptor (ER)-Positive breast cancers receive Standard T/FAC or T/FEC chemotherapy before surgery.
T/FAC or T/FEC: Combination chemotherapy with sequential paclitaxel (80 mg/m2) weekly x 12 weeks followed by 5-fluorouracil (500 mg/m2), cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) or epirubicin (100 mg/m2) (FAC or FEC) once every 3 weeks for 4 treatments.
Intervention: Cyclophosphamide (Drug)
Group 2: ER-Negative
Participants with ER-negative cancers (randomized between Group 2 & Group 3), Standard T/FAC or T/FEC chemotherapy before surgery.
Intervention: Paclitaxel (Drug)
Group 2: ER-Negative
Participants with ER-negative cancers (randomized between Group 2 & Group 3), Standard T/FAC or T/FEC chemotherapy before surgery.
Intervention: Fluorouracil (Drug)
Group 2: ER-Negative
Participants with ER-negative cancers (randomized between Group 2 & Group 3), Standard T/FAC or T/FEC chemotherapy before surgery.
Intervention: Doxorubicin (Drug)
Group 2: ER-Negative
Participants with ER-negative cancers (randomized between Group 2 & Group 3), Standard T/FAC or T/FEC chemotherapy before surgery.
Intervention: Epirubicin (Drug)
Group 2: ER-Negative
Participants with ER-negative cancers (randomized between Group 2 & Group 3), Standard T/FAC or T/FEC chemotherapy before surgery.
Intervention: Cyclophosphamide (Drug)
Group 3: ER-Negative + Bevacizumab
Participants with ER-negative cancers (randomized between Group 2 & Group 3), T/FEC chemotherapy combined with 10 mg Bevacizumab every 2 weeks during first 3 treatments before surgery.
Intervention: Paclitaxel (Drug)
Group 3: ER-Negative + Bevacizumab
Participants with ER-negative cancers (randomized between Group 2 & Group 3), T/FEC chemotherapy combined with 10 mg Bevacizumab every 2 weeks during first 3 treatments before surgery.
Intervention: Fluorouracil (Drug)
Group 3: ER-Negative + Bevacizumab
Participants with ER-negative cancers (randomized between Group 2 & Group 3), T/FEC chemotherapy combined with 10 mg Bevacizumab every 2 weeks during first 3 treatments before surgery.
Intervention: Epirubicin (Drug)
Group 3: ER-Negative + Bevacizumab
Participants with ER-negative cancers (randomized between Group 2 & Group 3), T/FEC chemotherapy combined with 10 mg Bevacizumab every 2 weeks during first 3 treatments before surgery.
Intervention: Cyclophosphamide (Drug)
Group 3: ER-Negative + Bevacizumab
Participants with ER-negative cancers (randomized between Group 2 & Group 3), T/FEC chemotherapy combined with 10 mg Bevacizumab every 2 weeks during first 3 treatments before surgery.
Intervention: Bevacizumab (Drug)
Outcomes
Primary Outcomes
Pathological Response Rate in Patients
Time Frame: Every 3-4 weeks during chemotherapy.
Response is defined as pathologic complete (pCR/RCB-0) or near complete (RCB-I) response pathologic finding after completion of chemotherapy.
Secondary Outcomes
No secondary outcomes reported