ZD6474 (Zactima) and Metronomic Chemotherapy in Advanced Breast Cancer

This study has been completed.
Sponsor:
Collaborators:
AstraZeneca
Massachusetts General Hospital
Brigham and Women's Hospital
Information provided by (Responsible Party):
Erica Mayer, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00496665
First received: July 3, 2007
Last updated: November 14, 2013
Last verified: November 2013
  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: Vandetanib
Drug: Cyclophosphamide
Drug: Methotrexate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of ZD6474 (Zactima) and Metronomic Chemotherapy in Advanced Breast Cancer

Resource links provided by NLM:


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 ]

Enrollment: 25
Study Start Date: July 2007
Study Completion Date: March 2009
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vandetenib
Cyclophosphamide 50 mg daily, methotrexate 2.5 mg days 1-2 weekly, and daily vandetanib (zactima) in 3 dose-escalation cohorts (100mg=Cohort 1) (200mg=Cohort 2) (300mg=Cohort3)
Drug: Vandetanib
Taken orally once a day in 28-day cycles (the dose will vary)
Other Names:
  • Zactima
  • Vandetanib
  • ZD6474
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00496665

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02215
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

No publications provided

Responsible Party: Erica Mayer, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00496665     History of Changes
Other Study ID Numbers: 06-402
Study First Received: July 3, 2007
Last Updated: November 14, 2013
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on July 28, 2014