Study Of Abraxane® And Carboplatin As First-Line Treatment For Triple Negative Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

Official title:

A Phase II Study of Abraxane® and Carboplatin as First-line Treatment for "Triple Negative" (Demonstrating no Expression for Estrogen, Progesterone, or Human Epidermal Growth Factor Receptor 2 (HER2)Receptors) Metastatic Breast Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01207102
• Other study ID #: Pro00019321
• Status: Terminated
• Phase: Phase 2
• First received: September 10, 2010
• Last updated: December 8, 2014
• Start date: August 2011
• Est. completion date: June 2014

Study information

• Verified date: August 2014
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Taxanes (such as paclitaxel) are highly active to treat breast cancer. Abraxane® (nanoparticle albumin-bound paclitaxel) compared to standard paclitaxel improves efficacy and tolerability. When combined with a taxane, platinum agents improve response in metastatic breast cancer, with carboplatin conferring less toxicity than cisplatin. The investigators hypothesize that the combination of weekly Abraxane® and carboplatin will lengthen time to progression without producing intolerable toxicity.

Description:

Paclitaxel and cisplatin are well-recognized for their activity in treating a variety of tumors including breast cancer. As cytotoxins, they have been studied alone and in combination with other chemotherapeutic agents, and have been incorporated into treatment regimens for women who fail previous anthracycline-based therapies. Although both agents are notable for favorable response rates, they are also associated with a variety of adverse events, some of which may be dose-limiting and having a negative effect on quality of life: myelosuppression, nausea and vomiting, diarrhea, stomatitis/mucositis, short- and long-term neuropathy, nephrotoxicity, alopecia and hypersensitivity reactions.

As second-generation compounds, Abraxane® and carboplatin have been shown to improve response rates and may mediate some of the toxicities associated with paclitaxel and cisplatin, respectively. Of particular interest is Abraxane's potential to reduce allergic reactions associated with other taxanes.

This study combines these two agents: primarily, to evaluate progression-free survival; and secondarily, to assess the feasibility and tolerability of this regimen to treat poor prognosis metastatic breast cancer patients.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with histologically or cytologically confirmed diagnosis of metastatic (Stage IV) breast cancer;

• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST);

• "Triple negative" disease defined as "tumor demonstrating no expression for estrogen, progesterone or HER2 receptors." (No expression is categorized as = 10% of cells staining or Allred = 2);

• Aged 18 years or older;

• Eastern Cooperative Oncology Group (ECOG)ECOG/Zubrod performance status of 0 or 1; life expectancy = 3 months;

• No prior chemotherapy for metastatic disease.

• At least 6 months must have elapsed since prior adjuvant chemotherapy.

• Laboratory tests performed within 14 days of study entry showing:

• Granulocytes = 1,500/µL;

• Platelets = 100,000/µL;

• Hemoglobin = 9.0 gm/dL;

• Total bilirubin = institutional upper limit of normal (ULN);

• Aspartate transaminase (AST) and alanine aminotransferase (ALT) = 2.5 times ULN;

• Alkaline phosphatase = 5 times ULN;

• Estimated creatinine clearance = 60 mL/min.

• Urine protein:creatinine ratio = 1.0. or 24 hour urine protein collection demonstrating = 1 gram of protein per 24 hours to be eligible.

• left ventricular ejection fraction (LVEF) = 50% by multiple gated acquisition scan (MUGA)/Echocardiogram;

• Informed consent to receive protocol treatment:

• Cognitive and communication skills adequate to comply with study and/or follow-up procedures;

• Geographic proximity and ability to comply with weekly study visits for the duration of the treatment;

• No reproductive potential:

• If pre-menopausal - Negative serum pregnancy test within 3 days prior to initiation of protocol-based treatment and patient agrees to use contraceptive method (abstinence, intrauterine device, barrier device with spermicide or surgical sterilization) during and for 3 months after completion of protocol treatment;

• If post-menopausal - Amenorrhea for = 12 months or follicle stimulating hormone (FSH) within post menopausal range.

Exclusion Criteria:

• Pregnant or breast feeding.

• Prior treatment with Abraxane® or carboplatin.

• Prior chemotherapy for metastatic breast cancer.

• Known hypersensitivity to any component of any study drug.

• Active infection.

• Current neuropathy = grade 2.

• central nervous system (CNS) metastases as determined by head CT with contrast or head MRI.

• Uncontrolled congestive heart failure (CHF), or history of myocardial ischemia (MI), unstable angina, stroke, or transient ischemia within previous 6 months.

• Uncontrolled serious contraindicated medical condition or illness.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Abraxane
Abraxane® 100 mg/m2 IV over 30 min days 1,8,15 every 28 days
• Carboplatin
area under curve(AUC)=2 over 15 minutes days 1,8,15 every 28 days

Locations

Country	Name	City	State
China	Peking University School of Oncology/Beijing Cancer Hospital	Beijing
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Celgene Corporation

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS	The primary objective of the trial is to statistically test whether Abraxane® and carboplatin can improve progression-free survival (PFS) as compared to historical controls.	PFS is defined as the interval from study registration to disease progression or death due to any cause, whichever comes first	No
Secondary	To Assess the Safety and Tolerability of a Combination Regimen of Weekly Abraxane® and Carboplatin to Treat Women With "Triple Negative" Stage IV Metastatic Breast Cancer	The proportion of patients experiencing any neurotoxicity will be tabulated by grade. The proportion of patients experiencing = grade 3 non-hematologic toxicities (excluding neurotoxicity) and the proportion of patients experiencing = grade 3 hematologic toxicities will be calculated with their exact 80% confidence intervals.	2 years	Yes