Study of Albumin-bound Paclitaxel (Abraxane) in Combination With Carboplatin and Herceptin in Patients With Advanced Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00093145
First received: October 4, 2004
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

This trial will treat patients with advanced breast cancer with a new anti-cancer medicine used in combination with two existing anti-cancer medications: Albumin-bound paclitaxel (ABI-007), Carboplatin and Herceptin. Participants will be given the combination therapy on a weekly basis and may continue on therapy as long as their condition improves and drug toxicity is tolerated.


Condition Intervention Phase
Breast Cancer
Drug: Albumin-bound paclitaxel
Drug: Carboplatin
Drug: Herceptin®
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 Study of Weekly Dose-Dense Nanoparticle Paclitaxel (ABI-007), Carboplatin With Herceptin® As First-Line Therapy of Advanced HER-2 Positive Breast Cancer

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Percentage of Participants Who Achieved an Objective Confirmed Complete or Partial Overall Response [ Time Frame: Objective response was evaluated every 2 cycles, up to a maximum of 39 cycles (approximately 39 months) ] [ Designated as safety issue: No ]
    Percentage of participants who achieved an objective confirmed complete or partial overall response based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. A complete response (CR) is the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation. A partial response (PR) is at least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters 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, or with the persistence of one or more non-target lesions and/or the maintenance of tumor marker level above the normal limits.


Secondary Outcome Measures:
  • Percentage of Participants With a Total Response [ Time Frame: Evaluated every 2 cycles, up to a maximum of 39 cycles. ] [ Designated as safety issue: No ]
    Total response was defined as the percentage of participants with stable disease (SD) for ≥ 16 weeks or complete or partial overall response. Stable disease was defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. Progressive disease is at least a 20% increase in the sum of the longest diameters of target lesions, 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.

  • Time to Disease Progression [ Time Frame: Assessed every 2 cycles, up to a maximum of 39 cycles. ] [ Designated as safety issue: No ]
    Time to disease progression was measured from the date of first dose of study drug to the start of disease progression. Patients who did not have disease progression at the end of follow-up were censored at the last known time that the patient was evaluated for progression. Progression is at least a 20% increase in the sum of the longest diameters of target lesions, 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. Time to disease progression was summarized using Kaplan-Meier methods.

  • Duration of Response [ Time Frame: Assessed every 2 cycles, up to a maximum of 39 cycles. ] [ Designated as safety issue: No ]
    Duration of response was evaluated by measuring progression-free survival for participants with a complete response or partial response. Progression-free survival was defined as the time from the first dose of study drug to the start of progression or patient death (whichever occurred first). Participants who did not have progression or were still alive were censored at the last known time the patient was progression free. Patients that initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Progression is at least a 20% increase in the sum of the longest diameters of target lesions, 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.

  • Overall Patient Survival [ Time Frame: From Day 1 until approximately 44 months. ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from the day of randomization to patient death (due to any cause), as assessed by post study follow-up on a monthly basis for 3 months and every 3 months. Participants still alive were censored at the last known time that the patient was alive. Patient survival was estimated using Kaplan-Meier methods.

  • Number of Participants With Adverse Events (AEs) [ Time Frame: Day 1 up to 39 cycles ] [ Designated as safety issue: Yes ]
    A Treatment-emergent AE was any AE that began or worsened after the start of study drug through 30 days after the last dose of study drug or end of study whichever is later. A treatment related toxicity was one considered by the investigator to be possibly, probably or definitely related to study drug. AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death. A serious adverse event (SAE) is any untoward medical occurrence at any dose that: is fatal or life-threatening; results in persistent or significant disability or incapacity; requires or prolongs in-patient hospitalization; is a congenital anomaly/birth defect in the offspring of a patient; and conditions not included in the above that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above


Enrollment: 32
Study Start Date: June 2004
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Albumin-bound paclitaxel, Carboplatin + Herceptin
Participants received albumin-bound paclitaxel, 100 mg/m^2 weekly every 3 out of 4 weeks, carboplatin at an area under the curve (AUC) = 6 every 4 weeks and Herceptin weekly, 4 mg/kg the first week and 2 mg/kg on all subsequent weeks by intravenous (IV) infusion for up to 6 cycles in the absence of disease progression or intolerable toxicity. Participants could continue treatment with chemotherapy beyond 6 cycles at the discretion of the investigator, but Herceptin therapy was to continue to be administered weekly (2 mg/kg) until intercurrent illness, disease progression, unacceptable toxicity, patient withdrawal or administration of any non-protocol anti-cancer treatment.
Drug: Albumin-bound paclitaxel
Administered by intravenous infusion.
Other Names:
  • ABI-007
  • ABRAXANE®
Drug: Carboplatin
Carboplatin dose was calculated using a modified Calvert formula (creatinine clearance was substituted for GFR): Total dose (mg) = (target AUC) x (creatinine clearance + 25). Note: AUC = 6 was initially targeted, but could be decreased due to toxicity.
Other Name: Paraplatin®
Drug: Herceptin®
Administered by IV infusion
Other Name: Trastuzumab

  Eligibility

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

Inclusion Criteria:

  • Confirmed adenocarcinoma of the breast
  • Tumor shows 3+ overexpression of the human epidermal growth factor receptor 2 (HER-2)/proto-oncogene by immunohistochemistry assay, or is fluorescence in situ hybridization (FISH)+
  • Stage IV disease
  • Measurable disease
  • At least 3 weeks since prior cytotoxic chemotherapy
  • At least 4 weeks since radiotherapy with full recovery
  • At least 4 weeks since major surgery with full recovery
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • At least 18 years old
  • Absolute neutrophil count (ANC) at least 1.5 x 10^9 cells/L
  • Platelets at least 100 x 10^9 cells/L
  • Hemoglobin at least 9 g/dL
  • Aspartame aminotransferase (AST), alanine aminotransferase (ALT) less than 2.5X upper limit normal
  • Alkaline Phosphatase less than 1.5X upper limit normal
  • Creatinine less than 1.5 gm/dL
  • Normal left ventricular ejection fraction
  • Negative pregnancy test
  • Agree to use method to avoid pregnancy
  • Informed Consent is obtained

Exclusion Criteria:

  • Up to one regimen of prior neo-adjuvant or adjuvant chemotherapy is allowed. One year since Taxane and Herceptin treatment.
  • Cumulative life-time dose of doxorubicin is greater than 360 mg/m^2
  • Concurrent immunotherapy or hormonal therapy
  • Parenchymal brain metastases, if present, must be documented to be clinically and radiographically stable for at least 6 months after treatment
  • Serious intercurrent medical or psychiatric illness, including serious active infection
  • History of congestive heart failure
  • History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer
  • Patients who have received an investigational drug within the previous 3 weeks
  • Patient is currently enrolled in another clinical study receiving investigational therapies
  • Pregnant or nursing women
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00093145

Locations
United States, California
Breastlink Med Group
Long Beach, California, United States, 90806
United States, Connecticut
Hematology/Oncology P.C. Carl & Dorothy Bennet Cancer Center
Stamford, Connecticut, United States, 06902
United States, District of Columbia
Lombardi Cancer Center Georgetown University Hospital
Washington, District of Columbia, United States, 2007
Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Florida
Florida Cancer Institute
Hudson, Florida, United States, 34667
Gulf Coast Oncology Associates
St. Petersburg, Florida, United States, 33705
Palm Beach Cancer Institute
West Palm Beach, Florida, United States, 33401
United States, Georgia
Gerogia Cancer Specialist
Atlanta, Georgia, United States, 30341
United States, Maine
Maine Center for Cancer Medicine and Blood Disorders
Scarbough, Maine, United States, 04074
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Pennsylvania
University of Pittsburgh Medical Center Magee Womens Hospital
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Texas
Southwest Regional Cancer Center
Austin, Texas, United States, 78705
United States, Washington
Swedish Medical Center Cancer Institute Research
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Celgene Corporation
Investigators
Principal Investigator: Andrew Seidman, MD Memorial Sloan-Kettering Cancer Center
  More Information

Publications:
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00093145     History of Changes
Obsolete Identifiers: NCT00085605
Other Study ID Numbers: CA016
Study First Received: October 4, 2004
Results First Received: May 7, 2013
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
Advanced Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014