Study of Albumin-bound Paclitaxel (Abraxane) in Combination With Carboplatin and Herceptin in Patients With Advanced Breast Cancer
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.
Drug: Albumin-bound paclitaxel
|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|
- 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.
- 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
|Study Start Date:||June 2004|
|Study Completion Date:||October 2008|
|Primary Completion Date:||October 2008 (Final data collection date for primary outcome measure)|
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: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
|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|
|Principal Investigator:||Andrew Seidman, MD||Memorial Sloan-Kettering Cancer Center|