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

Phase 1
18 Years
Open (Enrolling)
Metastatic Breast Cancer

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Trial Information

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

- 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

- 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

- 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.

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

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

Type of Study:


Study Design:

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

Outcome Measure:

To determine the safety and tolerability of combination therapy with ZD6474 (Zactima) and metronomic chemotherapy

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Erica Mayer, MD, MPH

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

July 2007

Completion Date:

June 2012

Related Keywords:

  • Metastatic Breast Cancer
  • Stage IV breast cancer
  • metronomic chemotherapy
  • Breast Neoplasms



Dana-Farber Cancer Institute Boston, Massachusetts  02115
Massachusetts General Hospital Boston, Massachusetts  02114-2617