Clinical Trials /

Preoperative Trial of Sorafenib in Combination With Cisplatin Followed by Paclitaxel for Early Stage Breast Cancer

NCT01194869

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Preoperative Trial of Sorafenib in Combination With Cisplatin Followed by Paclitaxel for Early Stage Breast Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: IRB00019781
  • SECONDARY ID: WCI1590-08
  • NCT ID: NCT01194869

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
SorafenibNexavarSorafenib
CisplatinPlatinol, CDDP, Cis-diamminedichloroplatinum(II)Sorafenib
PaclitaxelTaxolSorafenib

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.

Trial Arms

NameTypeDescriptionInterventions
SorafenibExperimentalSorafenib 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.
  • Sorafenib
  • Cisplatin
  • Paclitaxel

Eligibility 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 estrogen receptor (ER)-negative, progesterone receptor
             (PR)-negative, human epidermal growth factor receptor 2 (Her2)-negative. If breast
             cancer is Her2 2+ by immunohistochemistry (IHC), then fluorescence in situ
             hybridization (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 ≥ Common Toxicity Criteria for Adverse Effects
             (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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic Complete Response (pCR) at the Time of Surgery After Preoperative Treatment
Time Frame:At the time of surgery, after 24 weeks of preoperative treatment
Safety Issue:
Description:Pathologic complete response (pCR): Absence of invasive breast cancer in the breast (mastectomy or lumpectomy) specimen at the time of definitive surgery. Presence of in situ cancer alone will be considered a pCR but may be recorded separately.

Secondary Outcome Measures

Measure:Clinical Response Rate During Follow-up (Disease Recurrence)
Time Frame:Up to 2 years after definitive surgery
Safety Issue:
Description:Response will be assessed according to World Health Organization criteria with progressive disease (PD) defined as a 25% or greater increase in a single lesion, OR reappearance of any lesion which has disappeared, OR clear worsening of any evaluable disease OR appearance of any new lesion/site.
Measure:Clinical Response Rate (Complete Pathologic Response Rate After Surgery)
Time Frame:Up to 2 years after definitive surgery
Safety Issue:
Description:Pathologic complete response (pCR): Absence of invasive breast cancer in the breast (mastectomy or lumpectomy) specimen during follow-up. Presence of in situ cancer alone will be considered a pCR but may be recorded separately.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Emory University

Trial Keywords

  • Breast Cancer

Last Updated

August 31, 2016