ZD6474 (Zactima) and Metronomic Chemotherapy in Advanced Breast Cancer

• Status: Completed
• Trial end date: 2009-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this research study is to determine the safety and tolerability of the combination of Zactima with metronomic chemotherapy. Zactima is an oral anti-angiogenesis drug, which means it fights cancer by cutting off a tumor's blood supply. Thus, the drug starves the tumor by preventing the delivery of nutrients and oxygen. Metronomic chemotherapy is low dose oral chemotherapy pills which are taken daily. Unlike traditional chemotherapy, metronomic chemotherapy is thought to fight cancer like Zactima, by cutting off the blood supply to tumors. Because the dose is very low, the side effects are generally mild and very different from those with higher dose chemotherapy given by vein.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dana-Farber Cancer Institute
• Collaborators: AstraZeneca; Brigham and Women's Hospital; Massachusetts General Hospital
• Treatments: Cyclophosphamide; Methotrexate

Criteria

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed Stage IV breast cancer

• Patients may have prior treatment with 0-4 prior chemotherapeutic regimens for metastatic disease.

• 18 years of age and older

• Life expectancy of greater than 3 months as assessed by patient's primary oncologist

• ECOG Performance Status of 0-2.

• LVEF > 45%, as assessed by echocardiogram or nuclear medicine gate study within 30 days prior to initiating protocol-based treatment

• Negative Serum pregnancy test

• No receipt of any investigational agents within 30 days prior to commencing study treatment

Exclusion Criteria:

• Abnormal laboratory results as outlined in the protocol

• Therapeutic anti-coagulation. The use of low dose warfarin, intermittent doses of TPA, or heparin flushes to prophylax against central venous catheter associated clots is acceptable.

• Brain metastases or spinal cord compression, unless treated at least 4 weeks before entry and stable without steroid treatment for one week. Leptomeningeal disease is not eligible.

• Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate

• Clinically significant cardiac event such as myocardial infarction; NYHA classification of heart disease greater than or equal to 2; or presence of cardiac disease that increases the risk of ventricular arrhythmia

• History of arrhythmia which is symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia

• Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication

• Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age

• Presence of left bundle branch block

• QTc with Bazett's correction that is unmeasurable or greater than 480msec on screening ECG.

• Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function

• Hypertension not controlled by medical therapy

• Currently active diarrhea that may affect the ability of the patient to absorb the Zactima or tolerate diarrhea

• Previous or current non-breast malignancies within the last 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin

• Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy

• Patients with large or rapidly accumulating pleural or abdominal effusions

• Women who are currently pregnant or breastfeeding