Know Cancer

forgot password

Treatment of Malignant Pleural Effusion With ZD6474, a Novel Vascular Endothelial Growth Factor Receptor (VEGFR) and Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor

Phase 2
18 Years
Open (Enrolling)
Lung Cancer, Pleural Effusion

Thank you

Trial Information

Treatment of Malignant Pleural Effusion With ZD6474, a Novel Vascular Endothelial Growth Factor Receptor (VEGFR) and Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor

ZD6474 is an investigational drug that has not yet received approval from the FDA. ZD6474
is designed to limit VEGF. Vascular endothelial growth factor (VEGF) is considered to play
a key role in the development of pleural effusion. Pleural effusion is an abnormal
collection of pleural fluid in the pleural lining surrounding the lungs. The pleural lining
is the thin covering that protects and cushions the lungs. It is made up of two layers of
tissue that are separated by a small amount of fluid.

ZD6474 has shown promising activity against a number of cancers in laboratory tests in
animals with cancer and in some early clinical trials in patients with non-small cell lung
cancer (NSCLC). ZD6474 has also demonstrated significant reduction in pleural effusion in
association with VEGF inhibition of tumor cells in mice with lung tumors and pleural
effusion. It is hoped that ZD6474 will decrease the amount of pleural effusion that occurs
in NSCLC patients. In addition, ZD6474 is thought to block the formation of new blood
vessels, which may limit new blood vessel growth in the tumor and "starve" the tumor.

Before you can start treatment on this study, you will have "screening tests." These tests
will help the doctor decide if you are eligible to take part in this study. You will have a
complete physical exam, including measurement of vital signs (blood pressure, heart rate,
temperature, and breathing rate), height, and weight. You will be asked questions about
your ability to perform daily activities (performance status evaluation). You will have
blood (about 2-3 teaspoons) drawn for routine tests. You may have up to 3 electrocardiograms
(ECG --a test that measures the electrical activity of the heart). You will also have a
chest x-ray and computed tomography (CT) scans of your chest to measure the status of the
disease. You will be asked to fill out 2 questionnaires about the quality of your life and
shortness of breath. The questionnaires will take about 10-15 minutes, total, to complete.
Women who are able to have children must have a negative blood (about 1-2 teaspoons)
pregnancy test.

If you are found to be eligible to participate in the study, you will have an indwelling
intrapleural catheter placed. You will have to sign a separate consent document before
placement of an indwelling intrapleural catheter can be performed. The pleural fluid will
be collected at each clinic visit. The fluid will be saved and analyzed to answer research
questions that are part of this study. You will also need to drain your pleural fluid
everyday. The research nurse will provide you with instructions on how to drain your daily
pleural fluid and a patient "diary" to take home to record the amount of fluid drained every
day. The study doctor or research nurse will review the diary at each clinic visit.

After placement of the intrapleural catheter (Day 1), you will receive treatment with
ZD6474. Treatment on this study is for 10 weeks. You will take a ZD6474 tablet by mouth
each morning. The tablet should not be chewed, crushed, or divided, and should be taken with
8 ounces of water. You should take the tablet at about the same time every day.

During your participation on this study, you will have a physical exam, routine blood tests
and chest x-ray at Weeks 2, 6, and 10. At Weeks 6 and 10, you will also have a CT scan.
You will have an ECG at Weeks 1, 2, 4, and 8. Your doctor may decide to have additional
ECGs to monitor your condition or if you experience a heart rate of less than 50 at any time
during study participation. You will also be asked to complete 2 questionnaires about the
quality of your life and any shortness of breath you are experiencing. You will complete
these questionnaires at home and return them to the research staff at each clinic visit. You
will be asked to record your weekly blood pressure for the first 6 weeks of study treatment.
The study doctor or research nurse will review the log at each clinic visit.

If you are benefitting from the study treatment and your doctor feels that it is your best
interest, you may continue to receive the study drug longer than 10 weeks. During your
participation in this extended treatment phase, every 4 weeks you will have a physical exam
and your performance status will be evaluated. You will have blood (about 2-3 teaspoons)
drawn for routine tests. Every 4 weeks, you will have ECGs performed. You will also have a
chest x-ray and computed tomography (CT) scans of your chest to measure the status of the
disease every 8 weeks. Your study drug will continue to be provided to you.

You may be taken off study early if you have intolerable side effects or the disease gets

This is an investigational study. ZD6474, the investigational drug to be used in this
study, is not approved by the FDA for commercial use; however, the FDA has permitted its use
in this research study. Up to 25 patients will take part in this study. All will be
enrolled at M. D. Anderson.

Inclusion Criteria:

1. Patients with pleural effusion requiring placement of an indwelling intrapleural
denver catheter for recurrent symptomatic malignant pleural effusion

2. Pathologic documentation of NSCLC

3. Performance status 0 to 2 (Eastern Cooperative Oncology Group (ECOG) scale)

4. International Normalized Ratio (INR)
5. Signed informed consent prior to any study related procedures

6. Subject must be female or male age 18 years or over

Exclusion Criteria:

1. Chemotherapy or other anticancer therapy in the 3 weeks prior to study. Palliative
radiotherapy will be allowed to extra thoracic sites 2 weeks prior to study

2. No other prior malignancy is allowed except for adequately treated basal cell or
squamous cell skin cancer, in situ cervical cancer, or other cancer from which the
patient has been disease-free for at least two years

3. Laboratory results sustained at:Neutrophils less than 1.5x10^9/L or platelets less
than 100x10^9/L; Serum bilirubin >1.5 x the upper limit of reference range
(ULRR);Serum creatinine>1.5xULRR or CrCl Cockcroft-Gault formula). Potassium,<4.0 mmol despite supplementation;serum calcium
(ionized or adjusted for albumin),or magnesium out of normal range despite
supplementation;Alanine aminotransferase(ALT)or aspartate aminotransferase(AST) > 2.5
x ULRR or alkaline phosphatase(ALP)> 2.5 x ULRR,or > 5 x ULRR if judged by the
investigator to be related to liver metastases

4. Serious underlying medical condition that would impair the ability of the patient to
receive protocol treatment, specifically cardiac diseases, uncontrolled hypertension
or renal diseases

5. Diagnosis of post-obstructive pneumonia or other serious infection in the 14 days
prior to registration

6. Any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule

7. 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 in
the trial or which would jeopardize compliance with the protocol

8. Clinically significant cardiovascular event such as Myocardial infarction; New York
Heart Association (NYHA) classification of heart disease >/=2 within 3 months before
entry; or presence of cardiac disease that in the opinion of the Investigator
increase the risk of ventricular arrhythmia

9. History of arrhythmia (multifocal premature ventricular contractions (PVCs),
bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation)
which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained
ventricular tachycardia. Atrial fibrillation, controlled on medication is not

10. Previous history of QTc prolongation with other medication that required
discontinuation of that medication

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

12. QTc with Bazett's correction that is unmeasurable, or >/=480 msec on screening ECG.
If a patient has QTc >/=480 msec on screening ECG, the screen ECG may be repeated
twice (at least 24 hours apart). The average QTc from the three screening ECGs must
be <480 msec in order for the patient to be eligible for the study). Patients who are
receiving a drug that has a risk of QTc prolongation are excluded if QTc is >/= 460

13. Any concomitant medication that may cause QTc prolongation or induce Torsades de

14. Hypertension not controlled by medical therapy (systolic blood pressure greater than
160 mm Hg or diastolic blood pressure greater than 100 mm Hg)

15. Women who are currently pregnant or breast feeding

16. Participation in a clinical trial of any investigational agents within 30 days prior
to commencing study treatment

17. In 2nd line or later, the last dose of prior chemotherapy is discontinued less than 3
weeks before the start of study therapy

18. In 2nd line or later, the last radiation therapy discontinued less than 2 weeks
before the start of study therapy except palliative radiotherapy

19. If it is in 2nd line or later, any unresolved toxicity greater than CTC grade 1 from
previous anti-cancer therapy

20. Previous enrollment or randomization of treatment in the present study

21. Patients with pre-existing placement of intrapleural catheter

22. Presence of left bundle branch block (LBBB.)

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

24. Patients may not have a history of a bleeding diathesis

25. Currently active diarrhea that may affect the ability of the patient to absorb the
ZD6474 or tolerate diarrhea

26. Concomitant medications that are potent inducers (rifampicin, rifabutin, phenytoin,
carbamazepine, phenobarbital and St. John's Wort) of CYP3A4 function

Type of Study:


Study Design:

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

Outcome Measure:

Pleural Effusion Improvement (amount of pleural fluid drainage)

Outcome Time Frame:

Time from initiation of the treatment, i.e., time of inserting Denver catheter, to the removal of Denver catheter

Safety Issue:


Principal Investigator

Carlos Jimenez, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

October 2006

Completion Date:

October 2014

Related Keywords:

  • Lung Cancer
  • Pleural Effusion
  • Lung Cancer
  • Non-Small Cell Lung Cancer
  • Pleural Effusion
  • Indwelling Intrapleural Denver Catheter
  • ZD6474
  • Vascular Endothelial Growth Factor Receptor
  • Epidermal Growth factor Receptor
  • EGFR
  • Tyrosine Kinase Inhibitor
  • Lung Neoplasms
  • Pleural Effusion
  • Pleural Effusion, Malignant



UT MD Anderson Cancer Center Houston, Texas  77030