Clinical trial NCT00662129: Paclitaxel Albumin-Stabilized Nanoparticle Formulation, Gemcitabine, and Bevacizumab in Treating Patients With Metastatic Breast Cancer
Official title: Phase II Trial of Albumin-Bound Paclitaxel in Combination With Gemcitabine and Bevacizumab in Patients With Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage IV breast cancer
male breast cancer
recurrent breast cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-04-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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 overall survival of patients treated with this regimen.
* To determine the progression-free survival of patients treated with this regimen.
* To determine the confirmed response rate in patients treated with this regimen.
* To determine the duration of response in patients treated with this regimen.
* To determine the 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.

Eligibility criteria: 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

Primary outcomes:
measure: 6-month Progression-free Survival (PFS) Rate
timeFrame: at 6 months
Secondary outcomes:
measure: Overall Survival Time
timeFrame: Up to 5 years
measure: PFS Time
timeFrame: Up to 5 years
measure: Confirmed Response (Complete or Partial Response) Rate
timeFrame: Up to 5 years
measure: Duration of Response
timeFrame: Up to 5 years
measure: Time to Treatment Failure
timeFrame: Up to 5 years
measure: Quality of Life, as Measure by the Mean Change in FACT-B TOI Score at Cycle 8
timeFrame: From baseline to end of Cycle 8; Up to 24 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Hartford
country: United States
facility: Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services
state: Indiana
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Associates
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Regional Cancer Center at Mercy Medical Center
state: Iowa
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates - West Des Moines
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Mason City
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - North Iowa
state: Iowa
city: Ottumwa
country: United States
facility: McCreery Cancer Center at Ottumwa Regional
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Battle Creek
country: United States
facility: Battle Creek Health System Cancer Care Center
state: Michigan
city: Big Rapids
country: United States
facility: Mecosta County Medical Center
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Health Care
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Jackson
country: United States
facility: Foote Memorial Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Livonia
country: United States
facility: St. Mary Mercy Hospital
state: Michigan
city: Muskegon
country: United States
facility: Mercy General Health Partners
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Mercy Regional Cancer Center at Mercy Hospital
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute at Saint Mary's - Saginaw
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Hospital
state: Michigan
city: Alexandria
country: United States
state: Minnesota
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Duluth
country: United States
facility: Duluth Clinic Cancer Center - Duluth
state: Minnesota
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Duluth
country: United States
facility: Miller - Dwan Medical Center
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Maplewood
country: United States
facility: HealthEast Cancer Care at St. John's Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology, PA - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center - Minneapolis
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Clinic - River Campus
state: Minnesota
city: Saint Cloud
country: United States
facility: Coborn Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: St. Francis Cancer Center at St. Francis Medical Center
state: Minnesota
city: St. Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Willmar
country: United States
facility: Willmar Cancer Center at Rice Memorial Hospital
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology, PA - Woodbury
state: Minnesota
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Great Falls
country: United States
facility: Sletten Cancer Institute at Benefis Healthcare
state: Montana
city: Lincoln
country: United States
facility: Cancer Resource Center - Lincoln
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Omaha
country: United States
facility: Immanuel Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Alegant Health Cancer Center at Bergan Mercy Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Bismarck
country: United States
facility: Bismarck Cancer Center
state: North Dakota
city: Bismarck
country: United States
facility: Medcenter One Hospital Cancer Care Center
state: North Dakota
city: Bismarck
country: United States
facility: Mid Dakota Clinic, PC
state: North Dakota
city: Bismarck
country: United States
facility: St. Alexius Medical Center Cancer Center
state: North Dakota
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Franklin
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wilmington
country: United States
facility: Clinton Memorial Hospital
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at St. Francis Hospital
state: Oklahoma
city: Allentown
country: United States
facility: Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
Study officials:
affiliation: Mayo Clinic
name: Donald W. Northfelt, MD, FACP
role: STUDY_CHAIR
References:
citation: 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.