ZD6474 (Zactima) and Metronomic Chemotherapy in Advanced Breast Cancer

Metastatic Breast Cancer Clinical Trial

Official title:

A Phase I Study of ZD6474 (Zactima) and Metronomic Chemotherapy in Advanced Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00496665
• Other study ID #: 06-402
• Status: Completed
• Phase: Phase 1
• First received: July 3, 2007
• Last updated: November 14, 2013
• Start date: July 2007
• Est. completion date: March 2009

Study information

• Verified date: November 2013
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

• Each study cycle is 28 days long. Participants will take the study drug, Zactima, by mouth once a day. The dose of Zactima the participant will receive will be determined by the time when they enroll on the study. They will also take the metronomic chemotherapy by mouth. This consists of two drugs: cyclophosphamide and methotrexate. Cyclophosphamide is taken every day and methotrexate is taken on days 1 and 2 of each week.

• A physical exam will be performed on Day 1 of each cycle. Vital signs, including height, weight, blood pressure, and temperature will be done on Day 1 of each cycle, as well as at week 3 of Cycles 1 and 2.

• Electrocardiograms will be performed at various points to assess heart function. This will be done at week 1, 3, 5, 7, and 9, and then every 3 months for the rest of the study.

• Routine blood tests will be done on Day 1 of each cycle, as well as at week 3 for the first two cycles. Urine tests will be done on Day 1 of each cycle.

• An ultrasound will be done at Brigham and Women's Hospital in the Department of Vascular Medicine at week 3 and week 7.

• Participants will have scans done to assess their tumor every 2 cycles (8 weeks). These may include a CT scan, MRI, PET scan, x-rays, and/or bone scans.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: March 2009
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Vandetanib
Taken orally once a day in 28-day cycles (the dose will vary)
• Cyclophosphamide
Metronic Chemotherapy: Low dose pills taken every day of each 28-day cycle
• Methotrexate
Metronic Chemotherapy: low dose pills taken on days 1 and 2 of each week

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	AstraZeneca, Brigham and Women's Hospital, Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the safety and tolerability of combination therapy with ZD6474 (Zactima) and metronomic chemotherapy		2 years	Yes
Secondary	To determine the response rate of combination therapy with ZD6474 (Zactima) and metronomic chemotherapy in patients with measurable disease.		2 years	No