Therapy for Locally Advanced Breast Cancer Using Doxil, Paclitaxel, and Cyclophosphamide With Avastin
This study will evaluate the rate of response to the sequential therapy of Doxil, paclitaxel, and cyclophosphamide with concurrent Avastin for patients with locally advanced invasive (T2,T3, Nany, M0) breast carcinoma. Also, the study will evaluate the clinical and subclinical cardiotoxic effect(s) of this regimen, assess how feasible and safe the study is. Survival without any progression of disease will also be calculated.
A regimen of chemotherapy will be given to replicate the high rate of response in patients with locally advanced breast cancer. Doxil will substitute the normally given doxorubicin. It is expected that the low effect or minimal effect of Doxil on cardiac function will minimize any additional risk of cardiotoxicity from Avastin. It is expected that clinical and subclinical rates of cardiotoxicity will be very low at the total doses to be given in this clinical trial.
Invasive Breast Cancer
Drug: Doxil, Paclitaxel, Cyclophosphamide, Avastin
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Primary Systemic Therapy for Locally Advanced Breast Cancer Using Sequential Doxil, Paclitaxel, and Cyclophosphamide With Concurrent Avastin|
- The primary endpoint will be the rate of achievement of complete pathological response, to be determined by findings at surgery, i.e., segmental or total mastectomy. [ Time Frame: After completion of at least 8 of the 9 chemotherapy doses. ] [ Designated as safety issue: No ]Frequency and proportion will be used to report the overall complete pathological response rate.
- Evaluate clinical and subclinical cardiotoxicity [ Time Frame: Patients who receive any treatment drugs will be included for toxicity evaluation including cardiotoxicity. ] [ Designated as safety issue: Yes ]The change in left ventricular ejection fraction (LVEF) measurements from baseline to end of therapy will be used as well as clinical evaluations of cardiac toxicities.
- Assess toxicities of regimen including hand foot syndrome [ Time Frame: Patients who receive any treatment drugs will be included for toxicity evaluation ] [ Designated as safety issue: Yes ]Patients who receive any treatment drugs will be included for toxicity evaluation. Adverse events will be summarized with frequencies and proportions of study participants exhibiting adverse events. The severity of adverse events (none, mild, moderate, severe) and their relationship to the study product will be presented.
- Calculate progression free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]Progression free survival (PFS) will be defined as survival without local recurrence of breast cancer and without the development of distant metastasis. Death from any cause will be included as an event. The Kaplan-Meier nonparametric method will be used to estimate progression free survival.
|Study Start Date:||March 2008|
|Estimated Study Completion Date:||June 2019|
|Estimated Primary Completion Date:||June 2018 (Final data collection date for primary outcome measure)|
Experimental: Doxil, Paclitaxel, Cyclophosphamide + Avastin
Two staged phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil, paclitaxel and cyclophosphamide with concurrent Avastin in patients with locally advanced invasive breast cancer.
Drug: Doxil, Paclitaxel, Cyclophosphamide, Avastin
Regimen A: Sequential Doxil 25 mg/m2 every 2 weeks for 3 doses will be followed by paclitaxel 175 mg/m2 i.v. every 2 weeks for 3 doses, then by cyclophosphamide 600 mg/M 2 i.v. every 2 weeks for 3 doses. Avastin 10 mg/kg i.v. every 2 weeks will be given concurrently with all 3 agents. Patients who experience <pCR to primary chemotherapy will receive an additional year of Avastin at the same dose equivalent beginning 6-8 weeks after definitive operation.
Regimen B: Sequential Doxil 30 mg/m2 every 2 weeks for 3 doses will be followed by paclitaxel 175 mg/m2 i.v. every 2 weeks for 3 doses, then by cyclophosphamide 600 mg/m 2 i.v. every 2 weeks for 3 doses. Avastin 10 mg/kg i.v. every 2 weeks will be given concurrently with all 3 agents. Patients who experience <pCR to primary chemotherapy will receive an additional year of Avastin at the same dose equivalent beginning 6-8 weeks after definitive operation.
Other Name: Bevacizumab (Avastin)
In this trial, an attempt will be made to replicate the high rate of complete pathological response in patients with locally advanced breast cancer with a regimen in which Doxil is substituted for conventional doxorubicin. We expect that the low or minimal effect on cardiac function produced by Doxil will minimize any additional risk of cardiotoxicity from Avastin. We will also measure left ventricular ejection fractions before and after treatment to see if the substantial rate of subclinical cardiotoxicity reported by Swain et al5 and Perez et al7 can be avoided. The reported rates of cardiotoxicity after treatment with relatively high doses of Doxil are substantially lower than those of doxorubicin; few data are available to estimate the rate of cardiotoxicity of Doxil in patients treated with only about 100 mg/m2 total accumulated dose, the dose to be utilized here. The drug has been used in a few patients in the primary systemic therapy setting, with no reported clinical cardiotoxicity.
The expectation is that clinical and subclinical rates of cardiotoxicity will be very low or negligible at the total doses to be used here.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00635050
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35294 - 0104|
|Principal Investigator:||John Carpenter, M.D.||University of Alabama at Birmingham|