Phase II NCT w/ Weekly Abraxane in Combination With Carboplatin & Bevacizumab in Breast Cancer - Full Text View

Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and help kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bevacizumab after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying the side effects and how well giving paclitaxel albumin-stabilized nanoparticle formulation and carboplatin together with bevacizumab works in treating women undergoing surgery for stage II or stage III breast cancer.

Condition	Intervention	Phase
Breast Cancer	Drug: bevacizumab Drug: carboplatin Drug: nab-paclitaxel Procedure: Surgery Drug: Adjuvant chemotherapy	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Trial of Neoadjuvant Chemotherapy [NCT] With Weekly Nanoparticle Albumin-bound Paclitaxel [Nab-paclitaxel; Abraxane®] in Combination With Carboplatin and Bevacizumab in Women With Clinical Stages I-III Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Paclitaxel Carboplatin Bevacizumab

U.S. FDA Resources

Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:

Pathologic complete response (pCR) and side effects of weekly nab-paclitaxel, carboplatin and bevacizumab. [ Time Frame: every 4 weeks ] [ Designated as safety issue: No ]
Incidence of serious adverse events [ Time Frame: up to 32 days post study ] [ Designated as safety issue: Yes ]
Participants will either be seen in clinic or contacted by telephone to review adverse events, and this contact will be documented in the patient's medical record. The adverse events will be reviewed by the Investigator, who may choose to initiate further follow-up in clinic or through communication with the patient's primary physician or oncologist.

Secondary Outcome Measures:

Evaluation of dynamic contrast-enhanced magnetic resonance imaging in assessing pCR at baseline, after course 2 of neoadjuvant therapy, and after completion of neoadjuvant therapy (prior to definitive surgery) [ Time Frame: after 2 courses ] [ Designated as safety issue: No ]
Overall expression of LZTS1 as assessed by immunohistochemistry before and after neoadjuvant therapy [ Time Frame: prior to surgery ] [ Designated as safety issue: No ]

Estimated Enrollment:	33
Study Start Date:	July 2008
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Neoadjuvant Neoadjuvant chemotherapy : Nab-paclitaxel 100 mg/M2 IV and carboplatin AUC 2 IV on days 1, 8, and 15 in combination with bevacizumab 10 mg/kg on days 1 and 15 administered every 28 days [1 cycle] for 5 cycles followed by 1 cycle with Nab-paclitaxel 100 mg/M2 IV and carboplatin AUC 2 IV on days 1, 8, and 15.	Drug: bevacizumab bevacizumab 10 mg/kg on days 1 and 15 administered every 28 days [1 cycle] for 5 cycles Other Name: Avastin Drug: carboplatin AUC 2 IV on days 1, 8, and 15 Other Names: Paraplatin Paraplatin-AQ Drug: nab-paclitaxel 100 mg/M2 IV Other Name: Abraxane
Experimental: Adjuvant The use of additional adjuvant chemotherapy and/or radiation therapy depends upon the treating physicians' judgment. Radiation therapy should begin no sooner than 6 weeks after breast cancer surgery. All hormone receptor positive patients will receive endocrine therapy. All patients will receive 6 months of adjuvant bevacizumab at 15 mg/kg IV every 3 weeks. If using an adjuvant anthracycline-containing regimen then bevacizumab will be administered ≥ 3 weeks after completing the regimen.	Drug: Adjuvant chemotherapy All hormone receptor positive patients will receive endocrine therapy. All patients will receive 6 months of adjuvant bevacizumab at 15 mg/kg IV every 3 weeks. If using an adjuvant anthracycline-containing regimen then bevacizumab will be administered ≥ 3 weeks after completing the regimen.
Surgery Definitive surgery with either lumpectomy or mastectomy along with axillary lymph node dissection for all pre neoadjuvant chemotherapy node-positive patients approximately 4-5 weeks after the completion of NCT.	Procedure: Surgery lumpectomy or mastectomy along with axillary lymph node dissection approximately 4-5 weeks after completion of NCT.

Detailed Description:

OBJECTIVES:

Primary

To determine the complete pathological response (pCR) in the breast/axillary lymph nodes in women with stage II or III breast cancer treated with neoadjuvant therapy comprising paclitaxel albumin-stabilized nanoparticle formulation, carboplatin, and bevacizumab followed by surgery and adjuvant bevacizumab.
To determine the side effects of this regimen in these patients.

Secondary

To evaluate dynamic contrast-enhanced magnetic resonance imaging in assessing pCR.
To measure LZTS1 gene expression before and after neoadjuvant therapy to evaluate whether LZTS1 gene expression correlates with pCR.
To evaluate the feasibility and toxicity of adjuvant bevacizumab when administered for 6 months.

OUTLINE:

Neoadjuvant therapy: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and carboplatin IV over 30 minutes on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 5 courses. After completion of course 5, patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and carboplatin IV over 30 minutes on days 1, 8, and 15. Patients then proceed to surgery.
Surgery: Approximately 4-5 weeks after completion of neoadjuvant therapy, patients undergo definitive surgery (either lumpectomy or mastectomy). Patients with node-positive disease or inflammatory breast cancer at baseline also undergo axillary lymph node dissection. Patients then proceed to adjuvant therapy.
Adjuvant therapy: Beginning approximately 6 weeks after surgery, patients receive bevacizumab IV over 30-90 minutes once every 3 weeks for 6 months. Patients with hormone receptor-positive disease also receive endocrine therapy. Patients may also receive additional adjuvant chemotherapy or radiotherapy at the discretion of the treating physician.

Patients undergo dynamic contrast-enhanced magnetic resonance imaging at baseline, after course 2 of neoadjuvant therapy, and after completion of neoadjuvant therapy (prior to definitive surgery) for assessment of tumor response. Tumor tissue is collected at baseline and during surgery for correlative laboratory studies. LZST1 gene expression is assessed by immunohistochemistry before and after neoadjuvant therapy.

Eligibility

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

Criteria

Inclusion:

Histologically confirmed breast cancer
Clinically or radiographically measurable residual tumor after core biopsy
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Age ≥18 yrs
Absolute neutrophil count ≥ 1,500/mm³
Hemoglobin ≥ 9 g/dL
Platelet count ≥ 100,000/ mm³
Creatinine ≤ 1.5 times upper limit of normal (ULN)
Urine protein:creatinine ratio < 1.0
AST and ALT ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
Bilirubin normal
Women of childbearing potential must use effective contraception
Left ventricular ejection fraction (LVEF) normal by echocardiogram or MUGA

Exclusion:

No residual tumor after initial biopsy
Peripheral neuropathy of grade 2 or higher
HER-2 neu overexpression either by IHC 3+ or FISH+
No history of any prior treatment of breast cancer.
No history of unstable angina or myocardial infarction within the past 12 months
Pregnant or nursing women
Anticoagulation therapy within the last 6 months
History of gastrointestinal bleeding
Recent hemoptysis
No known hepatitis B or HIV seropositivity
No inadequately controlled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg and/or diastolic BP > 100 mm Hg despite antihypertensive medications
History of hypertensive crisis or hypertensive encephalopathy
New York Heart Association class II-IV congestive heart failure
History of stroke or transient ischemic attack at any time
Significant vascular disease (e.g., aortic aneurysm or aortic dissection)
No symptomatic peripheral vascular disease
Evidence of bleeding diathesis or coagulopathy
Significant traumatic injury within the past 28 days
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
Serious, non-healing wound, ulcer, or bone fracture
Known hypersensitivity to any component of bevacizumab

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00675259

Locations

United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210

Sponsors and Collaborators

Ewa Mrozek

Celgene Corporation

Genentech

Investigators

Principal Investigator:

Ewa Mrozek, MD

Ohio State University

More Information

Additional Information:

Jamesline

This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Ewa Mrozek, principal investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00675259 History of Changes
Other Study ID Numbers:	OSU-07074, NCI-2011-03188
Study First Received:	May 8, 2008
Last Updated:	May 22, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Ohio State University Comprehensive Cancer Center:

stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Adjuvants, Immunologic
Bevacizumab
Carboplatin
Paclitaxel
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

Antineoplastic Agents
Therapeutic Uses
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on May 21, 2013