Malignant Pleural Effusion With ZD6474
Condition: Lung Cancer; Pleural Effusion
MeSH terms: Lung Neoplasms; Pleural Effusion, Malignant; Pleural Effusion
Intervention: ZD6474
Intervention description: 300 mg/day orally for 10 weeks.
Intervention MeSH terms: Mitogens; Endothelial Growth Factors; Tyrosine Protein Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lung Cancer; Non-Small Cell Lung Cancer; Pleural Effusion; Indwelling Intrapleural Denver Catheter; ZD6474; Vascular Endothelial Growth Factor Receptor; VEGFR; Epidermal Growth factor Receptor; EGFR; Tyrosine Kinase Inhibitor

Summary:

      The goal of this clinical research study is to learn the effect of ZD6474 on the amount of
      time between placement of an indwelling pleural catheter and the catheter's removal in
      patients with malignant pleural effusion.

      This study will also look at the effect that ZD6474 has on tumor cells, biological
      characteristics of cells in the body, rate of fluid build-up around the lungs, tumor size,
      and thickness of blood vessels. The effect that this drug has on quality of life and
      shortness of breath will also be examined.
    

Eligibility criteria:

        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) </= 2.5

          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 </=30 mL/minute(calculated by 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 excluded

         10. Previous history of corrected QT interval (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
             msec

         13. Any concomitant medication that may cause QTc prolongation or induce Torsades de
             Pointes

         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