Therapy for Locally Advanced Breast Cancer Using Doxil, Paclitaxel, and Cyclophosphamide With Avastin
This study will evaluate the rate of pathological complete response (pCR) 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 pCR seen with conventional chemotherapy 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||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (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|
- Rate of Achievement of Pathological Complete Response (pCR) [ Time Frame: After completion of at least 8 of the 9 chemotherapy doses and operation. ]Results of the pathologic evaluation of the surgical specimen(s) from operation (segmental or total mastectomy) will be used to report the overall complete pathological response rate. Criteria used were those described by Kaufmann et al, Journal of Clinical Oncology 2003; 21(13):2600-2608. The definition of pCR used from this source was absence of invasive cancer in both resected breast tissue and in resected axillary nodes.
- Number of Participant With Clinical or Subclinical Cardiotoxicity [ Time Frame: Prior to treatment and at completion of chemotherapy ]Left ventricular ejection fraction (LVEF) measurements and clinical examination at baseline and at end of therapy will be used.
- Calculate Progression Free Survival [ Time Frame: 5 years ]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.
- Assess Toxicities of Regimen Including Hand Foot Syndrome [ Time Frame: Baseline, every 2 weeks during treatment, and at completion of therapy. Every 3 weeks during postoperative Avastin ]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 product will be presented.
|Study Start Date:||March 2008|
|Study Completion Date:||June 2015|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Doxil, Paclitaxel, Cyclophosphamide + Avastin
Two stage phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil 25 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, in patients with locally advanced invasive breast cancer.
Drug: Doxil, Paclitaxel, Cyclophosphamide, Avastin
Regimen A: Doxil 25 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3 . Patients who experience <pCR to primary chemotherapy will receive an additional year of Avastin 15 mg/kg iv every 3 weeks, beginning 6-8 weeks after operation.
Regimen B: Doxil 30 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3. Patients who experience <pCR to primary chemotherapy will receive an additional year of Avastin15 mg/kg iv every 3 weeks, beginning 6-8 weeks after operation.
Other Name: Bevacizumab (Avastin)
In this trial, an attempt will be made to replicate the high rate of pathological complete response seen after conventional chemotherapy in patients with locally advanced breast cancer, using 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 al 5 and Perez et al 7 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|