Paclitaxel Albumin-Stabilized Nanoparticle Formulation, Gemcitabine, and Bevacizumab in Treating Patients With Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

Phase II Trial of Albumin-Bound Paclitaxel in Combination With Gemcitabine and Bevacizumab in Patients With Metastatic Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00662129
• Other study ID #: NCCTG-N0735
• Secondary ID: NCI-2009-00666CD
• Status: Active, not recruiting
• Phase: Phase 2
• First received: April 18, 2008
• Last updated: August 12, 2016
• Start date: November 2008

Study information

• Verified date: August 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and paclitaxel albumin-stabilized nanoparticle formulation, 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 block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving paclitaxel albumin-stabilized nanoparticle formulation and gemcitabine together with bevacizumab works in treating patients with metastatic breast cancer.

Description:

OBJECTIVES:

Primary

• To determine the 6-month progression-free survival rate of patients with metastatic breast cancer treated with paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, and bevacizumab.

Secondary

• To determine the adverse event profile of this regimen.

• To determine the progression-free survival and overall survival of patients treated with this regimen.

• To determine the confirmed response rate, duration of response, and time to treatment failure in patients treated with this regimen.

• To determine the quality of life of patients treated with this regimen.

OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and after every other course, and then after completion of treatment.

After completion of study treatment, patients are followed periodically for 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 51
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed infiltrating breast cancer

• Clinical evidence of metastatic disease

• Measurable disease, defined as at least one measurable lesion per RECIST criteria

• No non-measurable disease only, defined as all other lesions, including small lesions (longest diameter < 2 cm) and truly non-measurable lesions, including any of the following:

• Bone lesions

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Inflammatory breast disease

• Lymphangitis cutis/pulmonis

• Abdominal masses that are not confirmed and followed by imaging techniques

• Cystic lesions

• Patients with HER-2/neu positive tumors, must have received prior treatment with trastuzumab (Herceptin®) or have a contraindication for trastuzumab

• No evidence of active brain metastasis, including leptomeningeal involvement, on MRI or CT scan

• CNS metastasis controlled by prior surgery and/or radiotherapy allowed

• Must be asymptomatic for = 2 months with no evidence of progression prior to study entry

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified

• Life expectancy = 12 weeks

• ECOG performance status 0-1

• ANC = 1,500/mm³

• Platelet count = 100,000/mm³

• Hemoglobin = 9.0 g/dL

• AST and ALT = 2.5 times upper limit of normal (ULN)

• Alkaline phosphatase = 2.5 times ULN

• Total bilirubin = 1.5 times ULN

• Creatinine = 1.5 mg/dL

• Urine protein:creatinine ratio < 1 or urinalysis < 1+ protein

• Patients discovered to have = 1+ proteinuria at baseline must demonstrate 24-hour urine protein < 1 g

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 30 days after completion of study therapy

• Able to complete questionnaires alone or with assistance

• No peripheral neuropathy > grade 1

• No history of allergy or hypersensitivity to albumin-bound paclitaxel, paclitaxel, gemcitabine hydrochloride, bevacizumab, albumin, drug product excipients, or chemically similar agents

• No stage III or IV invasive, non-breast malignancy within the past 5 years

• No other active malignancy, except nonmelanoma skin cancer or carcinoma in situ of the cervix

• Patient must not be receiving other specific treatment for a prior malignancy

• No uncontrolled hypertension (i.e., blood pressure [BP] > 160/90 mm Hg on = 2 occasions at least 5 minutes apart)

• Patients who have recently started or adjusted antihypertensive medications are eligible providing that BP is < 140/90 mm Hg on any new regimen for = 3 different observations in = 14 days

• No bleeding diathesis or uncontrolled coagulopathy

• No hemoptysis within the past 6 months

• No prior arterial or venous thrombosis within the past 12 months

• No history of cerebrovascular accident

• No history of hypertensive crisis or hypertensive encephalopathy

• No abdominal fistula or gastrointestinal perforation within the past 6 months

• No serious non-healing wound, ulcer, or fracture

• No clinically significant cardiac disease, defined as any of the following:

• Congestive heart failure

• Symptomatic coronary artery disease

• Unstable angina

• Cardiac arrhythmias not well controlled with medication

• Myocardial infarction within the past 12 months

• No comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for study entry or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior chemotherapy for metastatic disease

• May have received one prior adjuvant chemotherapy regimen

• Prior neoadjuvant chemotherapy allowed

• More than 6 months since prior adjuvant or neoadjuvant taxane (i.e., docetaxel or paclitaxel) therapy

• Prior hormonal therapy in either adjuvant or metastatic setting allowed

• More than 4 weeks since prior radiotherapy (except if to a non-target lesion only, or single dose radiation for palliation)

• Prior radiotherapy to a target lesion is allowed provided there has been clear progression of the lesion since radiotherapy was completed

• More than 4 weeks since prior cytotoxic chemotherapeutic agent or investigational drug

• More than 2 weeks since prior and no concurrent acetylsalicylic acid, anticoagulants, or thrombolytic agents (except for once-daily 81 mg acetylsalicylic acid)

• More than 6 weeks since prior major surgery, chemotherapy, or immunologic therapy

• More than 1 week since prior minor surgery (e.g., core biopsy)

• Placement of a vascular access device within 7 days is allowed

• More than 3 months since prior neurosurgery

• No concurrent treatment in a different clinical study in which investigational procedures are performed or investigational therapies are administered

• Trials related to symptom management (Cancer Control) which do not employ hormonal treatments or treatments that may block the path of the targeted agents used in this study may be allowed

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• bevacizumab

Drug:
• gemcitabine hydrochloride

• paclitaxel albumin-stabilized nanoparticle formulation

Locations

Country	Name	City	State
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Big Sky Oncology	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Wayne Hospital	Greenville	Ohio
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Mercy General Health Partners	Muskegon	Michigan
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Regions Hospital Cancer Care Center	St. Paul	Minnesota
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. John Macomb Hospital	Warren	Michigan
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	Metro Health Hospital	Wyoming	Michigan
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Northfelt DW, Dueck AC, Flynn TP, et al.: Phase II trial combining nab-paclitaxel (NP), gemcitabine (G), and bevacizumab (B) in patients (pts) with metastatic breast cancer (MBC): NCCTG N0735. [Abstract] J Clin Oncol 29 (Suppl 15): A-1126, 2011.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6-month progression-free survival (PFS) rate		at 6 months	No
Secondary	Survival time		Up to 5 years	No
Secondary	PFS time		Up to 5 years	No
Secondary	Confirmed response (complete or partial response)		Up to 5 years	No
Secondary	Duration of response		Up to 5 years	No
Secondary	Time to treatment failure		Up to 5 years	No
Secondary	Quality of life		Up to 5 years	No