Breast Cancer
Conditions
Keywords
Advanced Breast Cancer
Brief summary
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.
Interventions
DRUGAlbumin-bound paclitaxel
Administered by intravenous infusion.
DRUGCarboplatin
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.
DRUGHerceptin®
Administered by IV infusion
Sponsors
Celgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved an Objective Confirmed Complete or Partial Overall Response | Objective response was evaluated every 2 cycles, up to a maximum of 39 cycles (approximately 39 months) | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Total Response | Evaluated every 2 cycles, up to a maximum of 39 cycles. | 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 | Assessed every 2 cycles, up to a maximum of 39 cycles. | 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 | Assessed every 2 cycles, up to a maximum of 39 cycles. | 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 | From Day 1 until approximately 44 months. | 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) | Day 1 up to 39 cycles | 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 |
Countries
United States
Participant flow
Recruitment details
Due to slow patient accrual, only 32 patients of the planned 50 patients were enrolled. Patients were enrolled between June 2004 and July 2007.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other | 1 |
| Overall Study | Physician Decision | 5 |
| Overall Study | Unacceptable Toxicity Only | 2 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | Albumin-bound Paclitaxel, Carboplatin + Herceptin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age, Continuous | 52.0 years |
| Dominant Lesion Site (Target + Non-Target) Non visceral | 7 participants |
| Dominant Lesion Site (Target + Non-Target) Visceral | 25 participants |
| Dominant site of metastasis/relapse Non Visceral | 8 participants |
| Dominant site of metastasis/relapse Visceral | 24 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully Active) | 19 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restrictive but Ambulatory) | 12 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 (Ambulatory, but Unable to Work) | 1 participants |
| Histology of Primary Diagnosis Carcinoma/Adenocarcinoma | 31 participants |
| Histology of Primary Diagnosis Other | 1 participants |
| Menopausal Status Post-Menopausal | 25 participants |
| Menopausal Status Pre-Menopausal | 7 participants |
| Number of Lesions (Target + Non-Target) 0 or 1 lesion | 0 participants |
| Number of Lesions (Target + Non-Target) 2 to 3 lesions | 10 participants |
| Number of Lesions (Target + Non-Target) > 3 lesions | 22 participants |
| Physician assessment of peripheral neuropathy Grade 0 | 30 participants |
| Physician assessment of peripheral neuropathy Grade 1 | 1 participants |
| Race/Ethnicity, Customized Black, of African Heritage | 4 participants |
| Race/Ethnicity, Customized White, Hispanic or Latino | 2 participants |
| Race/Ethnicity, Customized White, Non-Hispanic and Non-Latino | 26 participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 0 Participants |
| Specific site(s) of metastasis/relapse Bone | 22 participants |
| Specific site(s) of metastasis/relapse Brain/Central Nervous System | 1 participants |
| Specific site(s) of metastasis/relapse Liver | 15 participants |
| Specific site(s) of metastasis/relapse Lung | 19 participants |
| Specific site(s) of metastasis/relapse Lymph Nodes | 24 participants |
| Specific site(s) of metastasis/relapse Other | 1 participants |
| Specific site(s) of metastasis/relapse Peritoneal | 1 participants |
| Specific site(s) of metastasis/relapse Skin/Soft Tissue/Breast | 21 participants |
| Time from first documented metastatic disease to study entry | 0.1 years |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 32 |
| serious Total, serious adverse events | 5 / 32 |
Outcome results
Primary
Percentage of Participants Who Achieved an Objective Confirmed Complete or Partial Overall Response
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.
Time frame: Objective response was evaluated every 2 cycles, up to a maximum of 39 cycles (approximately 39 months)
Population: The treated population consisted of all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albumin-bound Paclitaxel, Carboplatin + Herceptin | Percentage of Participants Who Achieved an Objective Confirmed Complete or Partial Overall Response | 62.5 Percentage of participants |
Secondary
Duration of Response
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.
Time frame: Assessed every 2 cycles, up to a maximum of 39 cycles.
Population: Treated Population - Patients with a Confirmed Complete or Partial Overall Response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Albumin-bound Paclitaxel, Carboplatin + Herceptin | Duration of Response | 17.8 months |
Secondary
Number of Participants With Adverse Events (AEs)
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
Time frame: Day 1 up to 39 cycles
Population: Treated population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albumin-bound Paclitaxel, Carboplatin + Herceptin | Number of Participants With Adverse Events (AEs) | Number with any treatment-related AE | 31 participants |
| Albumin-bound Paclitaxel, Carboplatin + Herceptin | Number of Participants With Adverse Events (AEs) | Number with any Grade 3/4 TEAE | 20 participants |
| Albumin-bound Paclitaxel, Carboplatin + Herceptin | Number of Participants With Adverse Events (AEs) | Number with any treatment emergent AE | 32 participants |
| Albumin-bound Paclitaxel, Carboplatin + Herceptin | Number of Participants With Adverse Events (AEs) | Number with any serious AE | 5 participants |
Secondary
Overall Patient Survival
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.
Time frame: From Day 1 until approximately 44 months.
Population: Treated population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Albumin-bound Paclitaxel, Carboplatin + Herceptin | Overall Patient Survival | NA months |
Secondary
Percentage of Participants With a Total Response
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 frame: Evaluated every 2 cycles, up to a maximum of 39 cycles.
Population: Treated population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albumin-bound Paclitaxel, Carboplatin + Herceptin | Percentage of Participants With a Total Response | 81.3 percentage of participants |
Secondary
Time to Disease Progression
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.
Time frame: Assessed every 2 cycles, up to a maximum of 39 cycles.
Population: Treated population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Albumin-bound Paclitaxel, Carboplatin + Herceptin | Time to Disease Progression | 16.6 months |