ABI-007 In Combination With Bevacizumab in Women With Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00394082
First received: October 30, 2006
Last updated: April 3, 2013
Last verified: October 2012
  Purpose

The purpose of this study is to evaluate the safety and tolerability of weekly ABI-007 in combination with bevacizumab.

The evaluation of progression-free survival of weekly ABI-007 in combination with bevacizumab for patients with previously untreated advanced/metastatic breast cancer.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: ABI-007
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Weekly Administration of ABI-007 In Combination With Bevacizumab in Women With Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Participants With At Least One Treatment-Emergent Adverse Event (TEAE) [ Time Frame: up to 25 months ] [ Designated as safety issue: Yes ]
    Count of study participants who had at least one treatment-emergent adverse event (TEAE) defined as any adverse event that began or worsened in grade after the start of study drug through 30 days after the last dose of study drug.

  • Kaplan-Meier Estimates for Progression-free Survival [ Time Frame: up to 39 months ] [ Designated as safety issue: No ]

    Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first. Patients who do not have disease progression or have not died at the end of follow-up were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.

    Response Evaluation Criteria in Solid Tumors (RECIST) defines progressive disease (PD) as a >= 20% increase taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.



Secondary Outcome Measures:
  • Percentage of Participants With Objective Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: up to 39 months ] [ Designated as safety issue: No ]
    Objective response is complete response (CR) + partial response (PR). RECIST defines overall response of CR as the disappearance of all target and non-target lesions and no appearance of new lesions, confirmed at least 4 weeks after initial documentation. Overall response of PR is defined as >= 30% decrease from baseline in the sum of the longest diameters of target lesions and no progression of non-target lesions and no appearance of new lesions, confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing and no appearance of new lesions. The objective response is determined by combining the response of target and non-target lesions and the appearance of new lesion(s) or not together.

  • Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: up to 39 months ] [ Designated as safety issue: No ]
    Disease control is stable disease (SD) for >=16 weeks + complete response (CR) + partial response (PR). RECIST defines SD as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease and no new lesions. Definitions for CR and PR can be found in outcome #3.

  • Kaplan-Meier Estimate for Duration of Response [ Time Frame: up to 39 months ] [ Designated as safety issue: No ]

    Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Patients that did not have progression or have not died were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.

    Progressive disease is defined in outcome #2. Complete response (CR) and partial response (PR) are defined in outcome #3.


  • Kaplan-Meier Estimates for Participant Survival [ Time Frame: up to 39 months ] [ Designated as safety issue: No ]
    Participant survival is the time from the first dose of study drug to patient death from any cause. Patients that did not die were censored at the last known time the patient was alive.


Enrollment: 50
Study Start Date: June 2006
Study Completion Date: February 2011
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ABI-007 plus Bevacizumab
ABI-007 is administered on days 1, 8 and 15 at 125 mg/m^2 and bevacizumab is administered on day 1 and 15 at 10 mg/kg of each 28 day cycle. Treatment continues until disease progression or intolerable toxicity. If a patient develops intolerable toxicity to only one of the drugs, the other drug may be continued as single agent therapy in the absence of progression, as long as the treating physician feels this is in the best interests of the patient.
Drug: ABI-007
125 mg/m^2 of ABI-007 administered by intravenously (IV) over 30 minutes on days 1, 8 and 15 of each 28 day cycle.
Other Names:
  • Abraxane®
  • Nab-paclitaxel
Drug: Bevacizumab
Bevacizumab administered once every 2 weeks (10 mg/kg) by IV infusion after ABI-007 has been given. The first dose is one Day 1, cycle 1.
Other Names:
  • NSC 704865
  • RhuMAb VEGF
  • Recombinant Humanized Monoclonal Bevacizumab Antibody

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically confirmed adenocarcinoma of the breast.
  • Stage IV disease.
  • Measurable disease (defined as the presence of at least one lesion that can be accurately measured in at least one dimension with longest diameter greater or = 1.0 cm with spiral computed tomography (CT) scan).
  • Patients must not be a candidate for Herceptin therapy (i.e., patients with HER-2 positive disease (gene amplification by fluorescence in situ hybridization (FISH) or 3 + overexpression by ICH) and patients with unknown HER-2 status are ineligible unless the treating physicians has determined that Herceptin-based therapy would be inappropriate or not indicated).
  • For subjects with prior anthracycline exposure, normal cardiac function including a baseline left ventricle ejection fraction >50% or above institution's lower limit of normal and a normal electrocardiogram (ECG) (as assessed by the investigator).
  • At least 2 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal or there must be pathologic proof of progressive disease within the radiation portal.
  • International Normalized Ratio (INR) < 1.5 and activated partial thromboplastin time within normal limits (APTT WNL).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Female > 18 years of age.
  • Patients have the following blood counts at Baseline: absolute neutrophil count (ANC) greater or equal to 1.5 x 10^9 cells/L; platelets greater or equal 100 x 10^9 cells/L; hemoglobin (Hgb) greater or equal to 9g/dL.
  • Patients have the following blood chemistry levels at Baseline: aspartate aminotransferase (AST or SGOT), alanine aminotransferase (ALT or SGPT) less than or equal 2.5x upper limit of normal (ULN) range (less than or equal 5x ULN if patient has known liver metastases); total bilirubin greater than or equal to ULN; creatinine greater or equal to 1.5mg/dL.
  • if female of childbearing potential, pregnancy test is negative within 72 hours of first dose of study drug.
  • if fertile, the patient agrees to use an effective method to avoid pregnancy for the duration of the study.
  • Informed consent has been obtained.

Exclusion Criteria:

  • No prior chemotherapy for metastatic or locally recurrent disease is allowed.
  • Prio neo-adjuvant chemotherapy is allowed, and patients must have recovered from the acute toxicity of such therapies.

    • if a taxane was part of the adjuvant regimen, at least 12 months must have elapsed between the last dose of the taxane and the date of diagnosis of metastatic disease.
    • if a non-taxane-based adjuvant therapy was administered, at least six months must have elapsed between the last dose of the non- taxane-containing chemotherapy and the date of diagnosis of metastatic disease.
  • Concurrent immunotherapy or hormonal therapy.
  • Parenchymal brain metastases, including leptomeningeal involvement.
  • Uncontrolled hypertension (defined as blood pressure of > 150/100 mmHg)
  • NYHA Grade 2 or greater congestive heart failure
  • History of coagulopathy, bleeding diathesis, therapeutic anticoagulation other than low dose or chronic ASA greater than or equal to 325 mg per day. Low dose coumadin for anticoagulation of venous access device or low dose molecular weight heparin (LMWH)for deep vein thrombosis prophylaxis or low dose (325 mg or less) ASA prophylaxis are allowed, but are best avoided if the treating physician feels it is safe to do so.
  • Urine protein:creatinine ratio less than or equal to 1.0 at screening.
  • No history of cerebrovascular accident within six months of study entry.
  • Active symptomatic peripheral vascular disease (e.g. aortic aneurysm, claudication) within six months of study entry.
  • Uncontrolled or severe cardiovascular disease including myocardial infarction or unstable angina within six months of study entry.
  • No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal process within six months of study entry.
  • No serious non-healing wound, ulcer, or bone fracture
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first dose, or anticipation of need for major surgical procedure during the course of the study. No minor surgical procedure within seven days of study entry. Serious intercurrent medical or psychiatric illness, including serious active infection.
  • History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.
  • Pregnant or nursing women.
  • Patients with current sensory neuropathy of > Grade 1 will be excluded.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00394082

Locations
United States, Florida
Melbourne, Florida, United States, 32901
Ocoee, Florida, United States, 34761
United States, Illinois
Niles, Illinois, United States, 60714
United States, Indiana
Terre Haute, Indiana, United States, 47802
United States, Maryland
Columbia, Maryland, United States, 21044
Westminister, Maryland, United States, 21157
United States, Missouri
St. Joseph, Missouri, United States, 64507
United States, New York
Rochester, New York, United States, 14623
United States, Texas
Bedford, Texas, United States, 76022
Dallas, Texas, United States, 75246
El Paso, Texas, United States, 79915
Odessa, Texas, United States, 79761
San Antonio, Texas, United States, 78229
Tyler, Texas, United States, 75702
United States, Virginia
Fairfax, Virginia, United States, 22031
Norfolk, Virginia, United States, 23502
Salem, Virginia, United States, 24153
United States, Washington
Burien, Washington, United States, 98166
Edmonds, Washington, United States, 98026
Vancouver, Washington, United States, 98684
Sponsors and Collaborators
Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00394082     History of Changes
Other Study ID Numbers: CA043
Study First Received: October 30, 2006
Results First Received: April 3, 2013
Last Updated: April 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
Metastatic breast cancer, Abraxane, Bevacizumab

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Bevacizumab
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014