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

NCT01194869 | Terminated Phase 2 Results DMC

• 2 other identifiers: IRB00019781WCI1590-08
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR) at the Time of Surgery After Preoperative Treatment

  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.

  At the time of surgery, after 24 weeks of preoperative treatment

Secondary Outcomes (2)

• Clinical Response Rate During Follow-up (Disease Recurrence)

  Up to 2 years after definitive surgery

• Clinical Response Rate (Complete Pathologic Response Rate After Surgery)

  Up to 2 years after definitive surgery

Study Arms (1)

Sorafenib

EXPERIMENTAL

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.

Drug: Sorafenib; Drug: Cisplatin; Drug: Paclitaxel

Interventions

Sorafenib DRUG

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.

Also known as: Nexavar

Sorafenib

Cisplatin DRUG

75 mg/m² given IV

Also known as: Platinol, CDDP, Cis-diamminedichloroplatinum(II)

Sorafenib

Paclitaxel DRUG

175 mg/m² given IV

Also known as: Taxol

Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead
• Amgen: collaborator
• Bayer: collaborator

Study Sites (3)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Sorafenib; Cisplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Results Point of Contact

• Title: Elisavet Paplomata, MD
• Organization: Emory University

elisavet.paplomata@emory.edu

404-778-1900

Study Officials

• Elisavet Paplomata, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 1, 2010
• First Posted: September 3, 2010
• Study Start: June 1, 2010
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: October 18, 2016
• Results First Posted: July 28, 2016

Record last verified: 2016-08

Locations

US (3)