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Preoperative Clinical Trial of Sorafenib in Combination With Cisplatin Followed by Paclitaxel for Triple Negative (ER-, PR-, Her2-) Early Stage Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Emory University
Sponsor:
Collaborators:
Onyx Pharmaceuticals
Bayer
Information provided by (Responsible Party):
Amelia Zelnak, Emory University
ClinicalTrials.gov Identifier:
NCT01194869
First received: September 1, 2010
Last updated: November 12, 2014
Last verified: November 2014
  Purpose

The purpose of this study is to identify new treatment regimens with better response rates and to find out if the combination of cisplatin and sorafenib followed by paclitaxel and sorafenib can shrink the size of your breast tumor and allow you to preserve your breast. Sorafenib is a newer drug that targets blood vessel formation and may help the chemotherapy work better. Additionally, by receiving chemotherapy before surgery, we will be able to determine if your cancer is responsive to chemotherapy.


Condition Intervention Phase
Breast Cancer
Drug: Sorafenib
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Neoadjuvant Trial of Sorafenib in Combination With Cisplatin Followed by Dose Dense Paclitaxel for ER-, PR-, Her2- (Triple Negative) Early-Stage Breast Cancer

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Rate of pathologic complete response rate at the time of surgery after preoperative treatment [ Time Frame: at the time of surgery, after 24 weeks of preoperative treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical response rate, safety, disease-free survival, overall survival [ Time Frame: during 24 weeks of therapy and during routine follow-up after study completion ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: June 2010
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: Sorafenib
Sorafenib 400 mg twice daily throughout the study. Patients will receive this as a single-agent for the first four weeks, then in combination with cisplatin followed by paclitaxel.
Other Name: Nexavar

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed invasive breast carcinoma.
  • Early stage breast cancer (Stage I (tumor size ≥ 1cm), II and IIIA).
  • Invasive breast cancer must be ER-negative, PR-negative, Her2-negative. If breast cancer is Her2 2+ by immunohistochemistry (IHC), then FISH must be negative for Her2 gene amplification.
  • No evidence of disease outside the breast or chest wall, except ipsilateral axillary lymph nodes.
  • Patients must have measurable disease as defined by palpable lesion with both diameters ≥ 1cm measurable with caliper and/or a positive mammogram or ultrasound with at least one dimension ≥ 1cm. Screening mammogram of the contralateral breast must be performed within past 12 months per standard practice guidelines. Clip placement is required for study entry. Baseline measurements of the indicator lesions must be recorded on the Patient Registration Form. To be valid for baseline, the measurements on clinical exam must have been made within 14 days if the mass is palpable. If the mass is not palpable, a mammogram or MRI must be done within 14 days. If the mass is palpable, a diagnostic mammogram of the affected breast or MRI must be done within 2 months prior to study entry.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 within 14 days of study entry.
  • Normal (greater than 50%) left ventricular ejection fraction (LVEF) by multigated acquisition (MUGA) scan or echocardiography.
  • Signed informed consent.
  • Adequate organ function within 2 weeks of study entry:

    • Absolute neutrophil count ≥ 1000/mm3, Hgb ≥ 9.0 g/dl and platelet count ≥ 100,000/mm3
    • Total bilirubin ≤ upper limit of normal
    • Creatinine ≤ 1.5 mg/dL or calculated creatinine clearance (CrCL) ≥ 50 mL/min using the Cockroft Gault equation
    • Serum glutamic oxaloacetic transaminase (SGOT)(AST) or serum glutamic pyruvic transaminase (SGPT)(ALT) and alkaline phosphatase must be within the range allowing for eligibility
  • Patients must be ≥ 18 years.
  • International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
  • Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation.
  • Patients with history of breast cancer greater than 5 years from initial diagnosis and are disease free are eligible for the study. Patients with history of ductal carcinoma in situ (DCIS) are eligible if there were treated with surgery alone.

Exclusion Criteria:

  • Prior chemotherapy, hormonal therapy, biologic therapy, investigational agent, targeted therapy or radiation therapy for current breast cancer.
  • Metastatic disease on baseline staging scans.
  • Medical, psychological or surgical condition which the investigator feels might compromise study participation.
  • History of previous or current malignancy at other sites with the exception of adequately treated carcinoma in-situ of the cervix or basal or squamous cell carcinoma of the skin. Patients with a history of other malignancies, who remain disease free for greater than five years are eligible.
  • Evidence of grade 2 or greater sensory and/or peripheral neuropathy.
  • Serious, uncontrolled, concurrent infection(s).
  • Major surgery within 4 weeks of the start of study treatment, without complete recovery.
  • Pregnant or lactating women are not eligible. Women or men of childbearing potential not using a reliable and appropriate contraceptive method are not eligible. (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential).
  • Use of St. John's Wort or rifampin (rifampicin).
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial.
  • Any condition that impairs patient's ability to swallow whole pills.
  • Any malabsorption problem.
  • Evidence or history of bleeding diathesis or coagulopathy.
  • Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug.
  • Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug.
  • Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  • Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
  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: NCT01194869

Contacts
Contact: Amelia Zelnak, MD 404-778-4824 amelia.zelnak@emory.edu

Locations
United States, Georgia
Emory University Hospital Midtown Recruiting
Atlanta, Georgia, United States, 30308
Contact: Regina Mosley    404-778-4824    rmosle3@emory.edu   
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Regina Mosley    404-778-4824    rmosle3@emory.edu   
Grady Memorial Hospital Recruiting
Atlanta, Georgia, United States, 30303
Contact: Regina Mosley    404-778-4824    rmosle3@emory.edu   
Sponsors and Collaborators
Emory University
Onyx Pharmaceuticals
Bayer
Investigators
Principal Investigator: Amelia Zelnak, MD Emory University
  More Information

No publications provided

Responsible Party: Amelia Zelnak, MD, Emory University
ClinicalTrials.gov Identifier: NCT01194869     History of Changes
Other Study ID Numbers: IRB00019781, WCI1590-08
Study First Received: September 1, 2010
Last Updated: November 12, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Emory University:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cisplatin
Paclitaxel
Sorafenib
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 20, 2014