The purpose of this study is to determine whether the treatment of a doxorubicin in combination with cyclophosphamide followed by a combination of pazopanib in combination with paclitaxel prior to surgery results in a pathological complete response in females with breast cancer.
This is a phase II non-randomized, multi-center study aimed to evaluate the efficacy and safety of the combination of pazopanib and paclitaxel following treatment with cyclophosphamide and doxorubicin for the treatment of neoadjuvant breast cancer. Patients will receive standard doses of AC every 21 days for 4 cycles. This will be followed by weekly paclitaxel 80 mg/m2 IV on Days 1, 8, and 15 every 28 days for 4 cycles given concurrently with pazopanib 800 mg PO daily starting with the first paclitaxel dose and continuing until 7 days before surgery. Clinical complete response rate will be determined by tumor assessments performed by palpation at two time points: following AC (before paclitaxel/pazopanib begins) and 2-4 weeks following the last dose of paclitaxel (before surgery). Following recovery from preoperative therapy, patients will undergo the clinically-indicated surgery. Pazopanib will resume 4-6 weeks after surgery and continue daily for 6 months of postoperative pazopanib therapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
101
4 cycles of doxorubicin + cyclophosphamide followed by 4 cycles of paclitaxel + pazopanib.
4 cycles of paclitaxel + pazopanib
neoadjuvant surgery for breast cancer
Number of Participants With Pathologic Complete Response (pCR) in the Breast and Nodes
pCR was defined as no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel node identified after neoadjuvant chemotherapy.
Time frame: From the start of the study until the time of surgery (average of 221.9 days [standard deviation of 23.65 days] after study entry)
Number of Participants With Pathologic Complete Response (pCR) in the Breast
pCR was defined as no histologic evidence of invasive tumor cells in the surgical breast specimen.
Time frame: From the start of the study until the time of surgery (average of 221.9 [standard deviation of 23.65 days] days after study entry)
Number of Participants With Clinical Complete Response (cCR) in the Breast and Nodes at the Completion of the Doxorubicin and Cyclophosphamide (AC) Period
cCR was determined by tumor assessments performed by palpation. All clinical response assessments were to be performed by physical examination of the breast and the axilla. cCR was defined as the resolution of all target and non-target lesions identified at Baseline and no new lesions or other signs of disease progression. The criteria to be used for the determination of progressive disease were at the investigator's discretion.
Time frame: From the start of the study until an average of 86.2 days (standard deviation of 5.76 days) after study entry
Number of Participants With Clinical CR (cCR) in the Breast and Nodes at the Completion of the AC and Weekly Paclitaxel (WP) + Pazopanib Preoperative Periods
cCR was determined by tumor assessments performed by palpation. All clinical response assessments were to be performed by physical examination of the breast and the axilla. cCR was defined as the resolution of all target and non-target lesions identified at Baseline and no new lesions or other signs of disease progression. The criteria to be used for the determination of progressive disease were at the investigator's discretion.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
6 months of treatment with pazopanib monotherapy
GSK Investigational Site
Decatur, Alabama, United States
GSK Investigational Site
Huntsville, Alabama, United States
GSK Investigational Site
Huntsville, Alabama, United States
GSK Investigational Site
Antioch, California, United States
GSK Investigational Site
Fremont, California, United States
GSK Investigational Site
Hayward, California, United States
GSK Investigational Site
Oakland, California, United States
GSK Investigational Site
Redwood City, California, United States
GSK Investigational Site
Richmond, California, United States
GSK Investigational Site
Roseville, California, United States
...and 133 more locations
Time frame: From the start of the study until the preoperative evaluation (an average of 203.0 days [standard deviation of 23.19 days] after study entry)
Invasive Recurrence-free Interval (IRFI)
IRFI was assessed as the time from study entry until the diagnosis of the first invasive local (evidence of invasive/in situ breast cancer \[except LCIS\] in the ipsilateral breast \[IB\]/skin of the breast), regional (development of tumor in the ipsilateral \[IP\] internal mammary, IP supraclavicular, IP infraclavicular, and/or IP axillary nodes, as well as the soft tissue of the IP axilla, following surgery), or distant (evidence of tumor in all areas, with the exception of those described for local and regional recurrence) breast cancer recurrence during the 24 months after study entry.
Time frame: up to 24 months after study entry
Number of Participants With Cardiac Toxicity (Per Common Terminology Criteria for Adverse Events Version 3) at the Completion of the AC Period
The number of participants with cardiac toxicity was defined as those who had cardiac events of Grades (G) 3 and 4 leftventricular dysfunction (LVD) (CTCAE Version 3.0) and/or who had definite or probable cardiac death. Grade refers to the severity of the AE: G 1, mild AE; G 2, moderate AE; G 3, severe AE; G 4, life-threatening/disabling AE; G 5, death related to the AE. A G3 LVD event is defined as symptomatic congestive heart failure (CHF) responsive to intervention. A G4 event is defined as poorly controlled refractory CHF; ventricular assist device or heart transplant indicated.
Time frame: From the start of the study until the preoperative evaluation (an average of 86.2 days [standard deviation of 5.76 days] after study entry)
Number of Participants With Cardiac Toxicity (Per CTCAE Version 3) at the Completion of the AC and Weekly Paclitaxel (WP) + Pazopanib Preoperative Periods
The number of participants with cardiac toxicity was defined as those who had cardiac events of Grades (G) 3 and 4 leftventricular dysfunction (LVD) (CTCAE Version 3.0) and/or who had definite or probable cardiac death. Grade refers to the severity of the AE: G 1, mild AE; G 2, moderate AE; G 3, severe AE; G 4, life-threatening/disabling AE; G 5, death related to the AE. A G3 LVD event is defined as symptomatic congestive heart failure (CHF) responsive to intervention. A G4 event is defined as poorly controlled refractory CHF; ventricular assist device or heart transplant indicated.
Time frame: From the start of the study until the preoperative evaluation (an average of 203.0 days [standard deviation of 23.19 days] after study entry).
Number of Participants With Cardiac Toxicity (Per CTCAE Version 3.0) During the Postoperative Pazopanib Period
The number of participants with cardiac toxicity was defined as those who had cardiac events of Grades (G) 3 and 4 leftventricular dysfunction (LVD) (CTCAE Version 3.0) and/or who had definite or probable cardiac death. Grade refers to the severity of the AE: G 1, mild AE; G 2, moderate AE; G 3, severe AE; G 4, life-threatening/disabling AE; G 5, death related to the AE. A G3 LVD event is defined as symptomatic congestive heart failure (CHF) responsive to intervention. A G4 event is defined as poorly controlled refractory CHF; ventricular assist device or heart transplant indicated.
Time frame: From the start of the study until the end of the postoperative pazopanib period, which coincides with the start of the end of treatment period (an average of 310.8 days [standard deviation of 85.29 days] after study entry)
Participants With Normal Thyroid Stimulating Hormone (TSH) Levels at Baseline Who Had an Elevated TSH Level at Least Once During the Study and During the Individual Study Periods
The number of participants with normal thyroid function at Baseline who had an elevation in TSH during the study were recorded. TSH elevation was derived based on local laboratory ranges.
Time frame: up to 24 months after study entry
Number of Participants With the Indicated Radiotherapy-related Complications
Time frame: up to 24 months after study entry
Number of Participants With Recurrence Events
The number of participants with recurrence events during the 24 months after study entry are reported. A recurrence event is defined as invasive local (evidence of invasive/in situ breast cancer \[except LCIS\] in the ipsilateral breast \[IB\]/skin of the breast), regional (development of tumor in the ipsilateral \[IP\] internal mammary, IP supraclavicular, IP infraclavicular, and/or IP axillary nodes, as well as the soft tissue of the IP axilla, following surgery), or distant (evidence of tumor in all areas, with the exception of those described for local and regional recurrence) breast cancer recurrence during the 24 months after study entry.
Time frame: up to 24 months after study entry