Phase II NCT w/ Weekly Abraxane in Combination With Carboplatin & Bevacizumab in Breast Cancer

This study has been completed.
Sponsor:
Collaborators:
Celgene Corporation
Genentech
Information provided by (Responsible Party):
Ewa Mrozek, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00675259
First received: May 8, 2008
Last updated: March 11, 2014
Last verified: March 2014
  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:


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 ]

Enrollment: 33
Study Start Date: July 2008
Study Completion Date: March 2014
Primary Completion Date: May 2011 (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
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: 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:
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: March 11, 2014
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
Bevacizumab
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014