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Therapy for Locally Advanced Breast Cancer Using Doxil, Paclitaxel, and Cyclophosphamide With Avastin

Information source: University of Alabama at Birmingham
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Invasive Breast Cancer

Intervention: Doxil, Paclitaxel, Cyclophosphamide, Avastin (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: University of Alabama at Birmingham

Official(s) and/or principal investigator(s):
John Carpenter, M.D., Principal Investigator, Affiliation: University of Alabama at Birmingham

Summary

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.

Clinical Details

Official title: Phase II Trial of Primary Systemic Therapy for Locally Advanced Breast Cancer Using Sequential Doxil, Paclitaxel, and Cyclophosphamide With Concurrent Avastin

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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.

Secondary outcome:

Evaluate clinical and subclinical cardiotoxicity

Assess toxicities of regimen including hand foot syndrome

Calculate progression free survival

Detailed description: 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.

Eligibility

Minimum age: 19 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Histologically confirmed, measurable, invasive breast carcinoma T >2cm, Nany, M0.

- Patients with node-negative, ER or PR-positive tumors ≤4 cm in size whose tumors are

low risk (defined as a score of 0-17) on an Oncotype DX profile are not eligible.

- 19 years of age or greater

- Known ER, PR and HER-2 status (FISH assay to be done on specimens with 2+ or 3+

immunohistochemical staining for HER-2): patients with gene amplification on FISH study will be considered to be HER-2 positive. Patients for this study must be FISH negative if immunohistochemical stain is 2+ or 3+ positive; patients with negative, 0 or 1+ immunohistochemical stain for HER-2 are eligible.

- Known axillary nodal status: aspiration cytology or biopsy

- Documented menopausal status premenopausal (having menstrual periods or FSH <35) or

postmenopausal (≥12 months since last menstrual period with intact uterus and at least one ovary or FSH ≥35 or previous bilateral oophorectomy

- Non-pregnant if premenopausal (negative serum or urine pregnancy test within 7 days

of starting chemotherapy) and not breast feeding

- Patients with reproductive potential must use an adequate contraceptive method (e. g.,

abstinence, intrauterine device, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment.

- Life expectancy of less than 12 weeks

- Current, recent (within 4 weeks of the first infusion of this study), or planned

participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study

- Pregnant or lactating women.

- History of cardiac disease, with New York Heart Association Grade II or greater or

clinical evidence of congestive heart failure.

- Serious comorbid medical conditions which would impair the ability to receive

chemotherapy on time

- Previous invasive cancer within the last 5 years

- Altered mental status or dementia which would interfere with understanding of

informed consent and ability to comply with study and follow-up procedures.

- Hypersensitivity to Doxil, doxorubicin, cyclophosphamide, cremaphore (contained in

teniposide, cyclosporine, and vitamin K), or to any component of Avastin

- Inadequately controlled hypertension (defined as blood pressure of >150/100 mmHg on

antihypertensive medication)

- Unstable angina pectoris

- History of myocardial infarction or unstable angina within 12 months prior to

beginning therapy

- History of stroke or TIA at any time

- Clinically significant vascular (e. g., aortic aneurysm requiring surgical repair or

recent peripheral arterial thrombosis, aortic dissection) or peripheral vascular disease with 6 months prior to beginning therapy

- History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per

episode) within 1 month prior to beginning therapy

- Evidence of bleeding diathesis or significant coagulopathy (in the absence of

therapeutic anticoagulation)

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days

prior to beginning therapy or anticipation of need for major surgical procedure during the course of the study

- Patients must have a 2-d echocardiogram indicating an ejection fraction of > 50%

within 42 days prior to first dose of study drug. The method used at baseline must be used for later monitoring.

- No distant metastases on bone scan and on CT scans of chest and abdomen (no

metastasis on optional PET scan is an acceptable alternative; if PET scan is done for any reason it must show no evidence of distant metastasis). Baseline PET scan is recommended but not required for all patients.

- No CNS metastasis

- Hbg ≥9 gm, platelets ≥100,000, granulocytes ≥1000, total or direct bilirubin ≤1. 2,

creatinine ≤2. 0 and urine protein: creatinine ratio <1. 0

- No prior chemotherapy or radiotherapy and ≤4 weeks of prior antiestrogen or aromatase

inhibitor therapy

- No concomitant hormone replacement (i. e. estrogen or progestin) therapy

- PS less than or equal to one

Exclusion Criteria:

- Minor surgical procedure (excluding placement of a vascular access device) such as

fine needle aspiration or core needle biopsy within 7 days of beginning therapy

- Urine protein: creatinine ratio ≥1. 0 at initial screening

- Known hypersensitivity to any component of Avastin

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal

abscess within 6 months of beginning therapy

- Serious, non-healing wound, active ulcer, or untreated bone fracture

- Any prior history of hypertensive crisis or hypertensive encephalopathy

- Known CNS metastasis, except for treated brain metastasis. Treated brain metastases

are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.

Locations and Contacts

University of Alabama at Birmingham, Birmingham, Alabama 35294 - 0104, United States
Additional Information

Starting date: March 2008
Last updated: July 1, 2014

Page last updated: August 20, 2015

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