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ZD6474 (Zactima) and Metronomic Chemotherapy in Advanced Breast Cancer
This study is currently recruiting participants.
Verified by Dana-Farber Cancer Institute, December 2007
Sponsors and Collaborators: Dana-Farber Cancer Institute
AstraZeneca
Massachusetts General Hospital
Brigham and Women's Hospital
Information provided by: Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00496665
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: ZD6474
Drug: Cyclophosphamide
Drug: Methotrexate
Phase I

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer
Drug Information available for: Cyclophosphamide Methotrexate Vandetanib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety Study
Official Title: A Phase I Study of ZD6474 (Zactima) and Metronomic Chemotherapy in Advanced Breast Cancer

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • To determine the safety and tolerability of combination therapy with ZD6474 (Zactima) and metronomic chemotherapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the response rate of combination therapy with ZD6474 (Zactima) and metronomic chemotherapy in patients with measurable disease. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: July 2007
Estimated Study Completion Date: July 2009
Estimated Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ZD6474
    Taken orally once a day in 28-day cycles (the dose will vary)
    Drug: Cyclophosphamide
    Metronic Chemotherapy: Low dose pills taken every day of each 28-day cycle
    Drug: Methotrexate
    Metronic Chemotherapy: low dose pills taken on days 1 and 2 of each week
Detailed 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00496665

Contacts
Contact: Erica Mayer, MD, MPH 617-632-3800 emayer@partners.org

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Erica Mayer, MD, MPH            
Principal Investigator: Harold Burstein, MD, PhD            
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Steven Isakoff, MD, PhD            
Sponsors and Collaborators
Dana-Farber Cancer Institute
AstraZeneca
Massachusetts General Hospital
Brigham and Women's Hospital
Investigators
Principal Investigator: Erica Mayer, MD, MPH Dana-Farber Cancer Institute
  More Information

Responsible Party: Dana-Farber Cancer Institute ( Erica Mayer, MD )
Study ID Numbers: 06-402
Study First Received: July 3, 2007
Last Updated: December 20, 2007
ClinicalTrials.gov Identifier: NCT00496665  
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Stage IV breast cancer
metronomic chemotherapy

Study placed in the following topic categories:
Folic Acid
Skin Diseases
Methotrexate
Breast Neoplasms
Cyclophosphamide
Breast Diseases

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Reproductive Control Agents
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Abortifacient Agents
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Alkylating Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009