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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00662129
First Posted: April 21, 2008
Last Update Posted: April 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
  Purpose

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.


Condition Intervention Phase
Breast Cancer Biological: bevacizumab Drug: gemcitabine hydrochloride Drug: paclitaxel albumin-stabilized nanoparticle formulation Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Albumin-Bound Paclitaxel in Combination With Gemcitabine and Bevacizumab in Patients With Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • 6-month Progression-free Survival (PFS) Rate [ Time Frame: at 6 months ]
    The primary endpoint of this trial is the 6-month progression-free survival rate. A patient is considered to be a 6-month progression-free survivor if the patient is 6 months from registration without a documentation of disease progression (note, the patient need not be on study treatment at 6 months to be considered a success). The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated using the properties of the binomial distribution. Progression is defined using the RECIST Criteria, as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.


Secondary Outcome Measures:
  • Overall Survival Time [ Time Frame: Up to 5 years ]
    Overall Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier (1958).

  • PFS Time [ Time Frame: Up to 5 years ]
    Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. The distribution of time to progression will be estimated using the method of Kaplan-Meier (1958). Progression is defined using the RECIST Criteria, as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.

  • Confirmed Response (Complete or Partial Response) Rate [ Time Frame: Up to 5 years ]
    A confirmed response is defined to be either a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 8 weeks apart. The confirmed response rate (percentage) will be estimated by the number of confirmed responses in evaluable patients divided by the total number of evaluable patients multiplied by 100. The appropriate confidence interval will be calculated based on the binomial distribution.

  • Duration of Response [ Time Frame: Up to 5 years ]
    Duration of response is defined for all evaluable patients who have achieved a confirmed response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented. If a patient dies subsequent to the confirmed response without a documentation of disease progression, the patient will be considered to have had disease progression at the time of their death. In the case of a patient failing to return for evaluations before a documentation of disease progression, the patient will be censored for progression on the date of last evaluation. The distribution of duration of response will be estimated using the method of Kaplan-Meier (1958).

  • Time to Treatment Failure [ Time Frame: Up to 5 years ]
    Time to treatment failure is defined to be the time from the date of registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. If the patient is considered to be a major treatment violation or is taken off study as a non-protocol failure, the patient will be censored on the date they were removed from treatment. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier (1958). Progression is defined using the RECIST Criteria, as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.

  • Quality of Life, as Measure by the Mean Change in FACT-B TOI Score at Cycle 8 [ Time Frame: From baseline to end of Cycle 8; Up to 24 weeks ]

    Quality of life (QOL) as measured by the mean change (from baseline) in FACT-B (TOI) Trial Outcome Index at Cycle 8 (24 weeks). FACT-B was scored according to the published scoring (*) criteria with higher scores representing better QOL. The FACT-B TOI was the sum of the following FACT-B subscale/scale scores: physical (score range 0-28), functional (score range 0-28), and Breast Cancer Subscale (score range 0-40); range of the FACT-B TOI is 0-96 (the change scores have a possible range of -96 to 96). The mean change and 95% confidence interval are reported below. A one-sample t-test is used to compare the change from baseline to a value of 0.

    (*)= Brady MJ, Cella DF, Mo F, Bonomi AE, Tulsky DS, Lloyd SR, Deasy S, Cobleigh M, Shiomoto G. Reliability and validity of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality of life instrument. J Clin Oncol 1997;15:974-986.



Enrollment: 50
Study Start Date: November 2008
Study Completion Date: August 2013
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: paclitaxel + gemcitabine + bevacizumab

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.

Biological: bevacizumab Drug: gemcitabine hydrochloride Drug: paclitaxel albumin-stabilized nanoparticle formulation

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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00662129


  Show 92 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Donald W. Northfelt, MD, FACP Mayo Clinic
  More Information

Publications:
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.

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00662129     History of Changes
Other Study ID Numbers: NCCTG-N0735
NCI-2009-00666 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
CDR0000593581 ( Registry Identifier: PDQ (Physician Data Query) )
First Submitted: April 18, 2008
First Posted: April 21, 2008
Results First Submitted: January 13, 2017
Results First Posted: April 17, 2017
Last Update Posted: April 17, 2017
Last Verified: March 2017

Keywords provided by Alliance for Clinical Trials in Oncology:
stage IV breast cancer
male breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Gemcitabine
Albumin-Bound Paclitaxel
Bevacizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors