Molecular Triaging of Newly Diagnosed Breast Cancer

This study has been withdrawn prior to enrollment.
(Recent developments lead to re-evaluation of study.)
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01159236
First received: July 7, 2010
Last updated: July 27, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention
Breast Cancer
Drug: Paclitaxel
Drug: Fluorouracil
Drug: Doxorubicin
Drug: Epirubicin
Drug: Cyclophosphamide
Drug: Bevacizumab

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Molecular Triaging of Newly Diagnosed Breast Cancer for Preoperative Therapies

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Pathological Response Rate in Patients [ Time Frame: Every 3-4 weeks during chemotherapy. ] [ Designated as safety issue: No ]
    Response is defined as pathologic complete (pCR/RCB-0) or near complete (RCB-I) response pathologic finding after completion of chemotherapy.


Enrollment: 0
Study Start Date: September 2010
Arms Assigned Interventions
Experimental: 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.

Drug: Paclitaxel
80 mg/m2 by vein over about 1-2 hours once every 7 days x 12 courses.
Other Name: Taxol
Drug: Fluorouracil
500 mg/m2 for 4 courses (once every 7 days)
Other Names:
  • 5-FU
  • Adrucil
  • Efudex
Drug: Doxorubicin
50 mg/m2 by vein given on day 1 and repeated once every 21 days for 4 treatments
Other Names:
  • Rubex
  • Adriamycin
Drug: Epirubicin
100 mg/m2 by vein given on day 1 and repeated once every 21 days for 4 treatments, may be given instead of Doxorubicin in Group 1 and 2.
Other Name: Ellence
Drug: Cyclophosphamide
500 mg/m2 by vein given on day 1 and repeated once every 21 days for 4 treatments.
Other Names:
  • Cytoxan
  • Neosar
Experimental: Group 2: ER-Negative
Participants with ER-negative cancers (randomized between Group 2 & Group 3), Standard T/FAC or T/FEC chemotherapy before surgery.
Drug: Paclitaxel
80 mg/m2 by vein over about 1-2 hours once every 7 days x 12 courses.
Other Name: Taxol
Drug: Fluorouracil
500 mg/m2 for 4 courses (once every 7 days)
Other Names:
  • 5-FU
  • Adrucil
  • Efudex
Drug: Doxorubicin
50 mg/m2 by vein given on day 1 and repeated once every 21 days for 4 treatments
Other Names:
  • Rubex
  • Adriamycin
Drug: Epirubicin
100 mg/m2 by vein given on day 1 and repeated once every 21 days for 4 treatments, may be given instead of Doxorubicin in Group 1 and 2.
Other Name: Ellence
Drug: Cyclophosphamide
500 mg/m2 by vein given on day 1 and repeated once every 21 days for 4 treatments.
Other Names:
  • Cytoxan
  • Neosar
Experimental: 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.
Drug: Paclitaxel
80 mg/m2 by vein over about 1-2 hours once every 7 days x 12 courses.
Other Name: Taxol
Drug: Fluorouracil
500 mg/m2 for 4 courses (once every 7 days)
Other Names:
  • 5-FU
  • Adrucil
  • Efudex
Drug: Epirubicin
100 mg/m2 by vein given on day 1 and repeated once every 21 days for 4 treatments, may be given instead of Doxorubicin in Group 1 and 2.
Other Name: Ellence
Drug: Cyclophosphamide
500 mg/m2 by vein given on day 1 and repeated once every 21 days for 4 treatments.
Other Names:
  • Cytoxan
  • Neosar
Drug: Bevacizumab
10 mg/kg intravenously every 2 weeks, discontinued 6 weeks before surgery (i.e. after 3rd course of FEC or FAC)
Other Names:
  • Avastin
  • Anti-VEGF monoclonal
  • rhuMAb-VEGF

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Patients must have intact cancer in the breast and intact regional lymph nodes (diagnostic core needle or fine needle biopsies are allowed).
  3. Routine estrogen, progesterone and HER-2 receptor determination must be performed before starting therapy.
  4. Patients with prior history of breast cancer are eligible.
  5. Patients with bilateral breast cancers are eligible.
  6. 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.
  7. Patients must agree to undergo pretreatment needle biopsy of the primary tumor in the breast for molecular profiling.
  8. Patients must agree to undergo surgery at MDACC and if assigned to bevacizumab containing chemotherapy it must be administered at MDACC.

Exclusion Criteria:

  1. 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
  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.
  3. Exclusion criteria for bevacizumab therapy; inadequately controlled hypertension (defined as systolic blood pressure >/= 140 mmHg and/or diastolic blood pressure >/= 90 mmHg).
  4. Exclusion criteria for bevacizumab therapy, prior history of hypertensive crisis or hypertensive encephalopathy, stroke or transient ischemic attacks.
  5. Exclusion criteria for bevacizumab therapy, history of myocardial infarction, unstable angina or congestive heart failure within 12 months prior to starting therapy.
  6. Exclusion criteria for bevacizumab therapy, aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis within 6 months prior to starting therapy.
  7. 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).
  8. 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.
  9. Exclusion criteria for bevacizumab therapy, history of abdominal fistula or gastrointestinal perforation within 6 months prior to starting therapy.
  10. Exclusion criteria for bevacizumab therapy, serious, non-healing wound or fracture or active ulcer.
  11. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01159236

Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Lajos Pusztai, MD, DPHIL UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01159236     History of Changes
Other Study ID Numbers: 2008-0765
Study First Received: July 7, 2010
Last Updated: July 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Gene signatures
HER-2 normal stage I-III breast cancer
Estrogen Receptor
ER-positive
ER-negative
RCB categories II-III
Neoadjuvant Chemotherapy
adjuvant systemic therapy
molecular testing
Fluorouracil
5-fluorouracil
5-FU
Doxorubicin
Adriamycin
Rubex
Epirubicin
Ellence
Cyclophosphamide
Cytoxan
Neosar
Bevacizumab
Avastin
Anti-VEGF monoclonal
rhu-MAb-VEGF

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Bevacizumab
Cyclophosphamide
Doxorubicin
Epirubicin
Fluorouracil
Liposomal doxorubicin
Paclitaxel
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 29, 2014