Phase II NCT (Neoadjuvant Chemotherapy) w/ Weekly Abraxane in Combination With Carboplatin & Bevacizumab in Breast Cancer

NCT00675259 | Completed Phase 2 Results DMC

• 2 other identifiers: OSU-07074NCI-2011-03188
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Pathologic Complete Response (pCR)

  pCR was defined as the absence of viable invasive tumor cells in the surgical breast specimen and axillary lymph nodes.

  every 4 weeks

• Side Effects of Weekly Nab-paclitaxel, Carboplatin and Bevacizumab

  Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0

  Up to 4 weeks

Secondary Outcomes (2)

• Evaluation of Dynamic Contrast-enhanced Magnetic Resonance Imaging in Assessing pCR at Baseline and After 2 Cycles of Neoadjuvant Therapy

  after 2 cycles of therapy

• Overall Expression of LZTS1 Before and After Neoadjuvant Therapy as Assessed by Immunohistochemistry

  prior to surgery

Study Arms (1)

Neoadjuvant, Surgery, Adjuvant

EXPERIMENTAL

Neoadjuvant chemotherapy : Nab-paclitaxel and carboplatin on days 1, 8, and 15 in combination with bevacizumab on days 1 and 15 administered every 28 days for 5 cycles followed by 1 cycle with Nab-paclitaxel and carboplatin on days 1, 8, and 15. Definitive surgery with either lumpectomy or mastectomy along with axillary lymph node dissection for all pre neo adjuvant chemotherapy node-positive patients approximately 4-5 weeks after the completion of NCT. 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 every 3 weeks. If using an adjuvant anthracycline-containing regimen then bevacizumab will be administered ≥ 3 weeks after completing the regimen.

Drug: bevacizumab; Drug: carboplatin; Drug: nab-paclitaxel; Procedure: Surgery; Drug: Adjuvant chemotherapy

Interventions

bevacizumab DRUG

bevacizumab 10 mg/kg on days 1 and 15 administered every 28 days \[1 cycle\] for 5 cycles

Also known as: Avastin

Neoadjuvant, Surgery, Adjuvant

carboplatin DRUG

AUC 2 IV on days 1, 8, and 15

Also known as: Paraplatin, Paraplatin-AQ

Neoadjuvant, Surgery, Adjuvant

nab-paclitaxel DRUG

100 mg/M2 IV

Also known as: Abraxane

Neoadjuvant, Surgery, Adjuvant

Surgery PROCEDURE

lumpectomy or mastectomy along with axillary lymph node dissection approximately 4-5 weeks after completion of NCT.

Neoadjuvant, Surgery, Adjuvant

Adjuvant chemotherapy DRUG

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.

Neoadjuvant, Surgery, Adjuvant

Eligibility Criteria

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

You may qualify if:

• 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 (aspartate aminotransferase) 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• Celgene Corporation: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Mrozek E, Layman R, Ramaswamy B, Lustberg M, Vecchione A, Knopp MV, Shapiro CL. Phase II trial of neoadjuvant weekly nanoparticle albumin-bound paclitaxel, carboplatin, and biweekly bevacizumab therapy in women with clinical stage II or III HER2-negative breast cancer. Clin Breast Cancer. 2014 Aug;14(4):228-34. doi: 10.1016/j.clbc.2014.02.005. Epub 2014 Feb 20.

  PMID: 24703985 RESULT

Related Links

• Jamesline

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab; Carboplatin; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Surgical Procedures, Operative; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Combined Modality Therapy; Therapeutics; Drug Therapy

Results Point of Contact

• Title: Ewa Mrozek, MD
• Organization: The Ohio State University

Ewa.mrozek@osumc.edu

614-293-0066

Study Officials

• Ewa Mrozek, MD

  Ohio State 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: SPONSOR

Study Record Dates

• First Submitted: May 8, 2008
• First Posted: May 9, 2008
• Study Start: July 1, 2008
• Primary Completion: May 1, 2011
• Study Completion: March 1, 2014
• Last Updated: July 24, 2018
• Results First Posted: August 24, 2016

Record last verified: 2018-06

Locations

US (1)