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Malignant Pleural Effusion With ZD6474

Primary Purpose

Lung Cancer, Pleural Effusion

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ZD6474
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UT MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ZD6474

Arm Description

300 mg/day orally for 10 weeks.

Outcomes

Primary Outcome Measures

Median Time to Pleurodesis
Time to pleurodesis from initiation of treatment to catheter removal as measure of pleural effusion Improvement (amount of pleural fluid drainage) where objective was to examine whether ZD6474 would help participants to improve the condition of pleural effusion, and thus remove the catheter earlier. Cox model analysis applied to examine the effect of covariates on the time to catheter removal.

Secondary Outcome Measures

Full Information

First Posted
November 20, 2006
Last Updated
February 11, 2016
Sponsor
M.D. Anderson Cancer Center
Collaborators
United States Department of Defense, AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT00402896
Brief Title
Malignant Pleural Effusion With ZD6474
Official Title
Treatment of Malignant Pleural Effusion With ZD6474, a Novel Vascular Endothelial Growth Factor Receptor (VEGFR) and Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Terminated
Why Stopped
Slow Accrual
Study Start Date
October 2006 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
United States Department of Defense, AstraZeneca

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed Description
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 worse. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer, Pleural Effusion
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ZD6474
Arm Type
Experimental
Arm Description
300 mg/day orally for 10 weeks.
Intervention Type
Drug
Intervention Name(s)
ZD6474
Other Intervention Name(s)
Vascular Endothelial Growth Factor Receptor, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor
Intervention Description
300 mg/day orally for 10 weeks.
Primary Outcome Measure Information:
Title
Median Time to Pleurodesis
Description
Time to pleurodesis from initiation of treatment to catheter removal as measure of pleural effusion Improvement (amount of pleural fluid drainage) where objective was to examine whether ZD6474 would help participants to improve the condition of pleural effusion, and thus remove the catheter earlier. Cox model analysis applied to examine the effect of covariates on the time to catheter removal.
Time Frame
Time from initiation of treatment and catheter insertion up to a maximum of 10 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with pleural effusion requiring placement of an indwelling intrapleural denver catheter for recurrent symptomatic malignant pleural effusion Pathologic documentation of NSCLC Performance status 0 to 2 (Eastern Cooperative Oncology Group (ECOG) scale) International Normalized Ratio (INR) </= 2.5 Signed informed consent prior to any study related procedures Subject must be female or male age 18 years or over Exclusion Criteria: 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 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 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 Serious underlying medical condition that would impair the ability of the patient to receive protocol treatment, specifically cardiac diseases, uncontrolled hypertension or renal diseases Diagnosis of post-obstructive pneumonia or other serious infection in the 14 days prior to registration Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule 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 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 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 Previous history of corrected QT interval (QTc) prolongation with 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 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 Any concomitant medication that may cause QTc prolongation or induce Torsades de Pointes Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg) Women who are currently pregnant or breast feeding Participation in a clinical trial of any investigational agents within 30 days prior to commencing study treatment In 2nd line or later, the last dose of prior chemotherapy is discontinued less than 3 weeks before the start of study therapy In 2nd line or later, the last radiation therapy discontinued less than 2 weeks before the start of study therapy except palliative radiotherapy If it is in 2nd line or later, any unresolved toxicity greater than CTC grade 1 from previous anti-cancer therapy Previous enrollment or randomization of treatment in the present study Patients with pre-existing placement of intrapleural catheter Presence of left bundle branch block (LBBB.) Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy Patients may not have a history of a bleeding diathesis Currently active diarrhea that may affect the ability of the patient to absorb the ZD6474 or tolerate diarrhea Concomitant medications that are potent inducers (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort) of CYP3A4 function
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlos Jimenez, M.D.
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UT MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24913066
Citation
Massarelli E, Onn A, Marom EM, Alden CM, Liu DD, Tran HT, Mino B, Wistuba II, Faiz SA, Bashoura L, Eapen GA, Morice RC, Jack Lee J, Hong WK, Herbst RS, Jimenez CA. Vandetanib and indwelling pleural catheter for non-small-cell lung cancer with recurrent malignant pleural effusion. Clin Lung Cancer. 2014 Sep;15(5):379-86. doi: 10.1016/j.cllc.2014.04.002. Epub 2014 May 14.
Results Reference
derived
Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website

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Malignant Pleural Effusion With ZD6474

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