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Study Summary
No. SWOGS0509:.......Lung......Anne S. Tsao......Thoracic and Head and Neck Med
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Study Summary Title
Study Summary
Number:
SWOGS0509
Study Title:A Phase II Trial Of Novel Oral Anti-Angiogenic Agent AZD2171 (NSC-732208) In Malignant Pleural Mesothelioma
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Physician New Patient Referral
Name:Anne S. TsaoPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Thoracic and Head and Neck MedReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-6363
Contact us about clinical trials
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General Information
Disease Group:LungSupported By:N/A
Phase of Study:Phase IIReturn
Visit:
Every 6 months for the first two years and then once a year for up to three
years from the time the study is started.
Treatment
Agents:
AZD2171Home Care:N/A
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to learn if AZD2171 can help to
control
malignant pleural mesothelioma. The safety of this treatment will also be
studied.
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Study Objectives / Outcomes
1. 1 Primary Objective:
To assess the objective response rate (confirmed, complete and partial response rate) in patients with unresectable malignant pleural mesothelioma treated with AZD2171.

1. 2 Secondary Objectives:
a. To assess response via modified RECIST for pleural tumors.
b. To assess clinical benefit (objective response rate plus stable disease rate)
c. To assess the I-year and median overall survival.
d. To assess progression-free survival.
e. To evaluate the frequency and severity of toxicities associated with this treatment regimen.
f. To measure molecular correlates of the VEGF-mediated signaling pathway (tumor expression of VEGF and its receptors).
g. To measure pre- and post-treatment plasma VEGF and soluble VCAM and to correlate these measures in preliminary fashion with clinical outcomes.
h. To measure expression of phosphorylated VEGFRl and R2 in pre- and posttreatment fresh tumor biopsies in a select number of patients.
i. To perform pharmacogenetic analyses of variants of genes in the pathway targeted by AZD2171, including KDRIFLK-1 (the specific target of AZD2171), VEGF-A, HlFla and p53 and of variants of candidate genes involved in the development of hypertension in relation to antiangiogenic therapy.
j. To measure circulating endothelial cells (CECs) and to correlate in an exploratory manner this measure with the aforementioned clinical outcomes.
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Study Status Information
Study Activation / Registration Date:10/24/2006
IRB Review and Approval Date:08/02/2006
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Terminated
Projected Accrual:40
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Patients must have histologically confirmed diagnosis of unresectable malignant pleural mesothelioma. Patients must have either epithelial, sarcomatous or biphasic histologic subtypes.

2) All patients must be 18 years of age or older as AZD2171 increases the hypertrophic zone of the epiphyseal growth plates in animal studies.

3) Patients must have measurable disease per RECIST criteria documented by imaging (CT or MRI) examination within 28 days prior to registration. Non-measurable disease must be assessed within 42 days prior to registration.

4) Patients must have had prior systemically administered platinum-based chemotherapy. Patients must have had only one regimen of platinum. Patients may have received more than one drug concurrent with the one allowed platinum-based regimen. Pleural space washing with cisplatin does not constitute systemic administration. One prior chemotherapy regimen only is allowed. Patients must have completed chemotherapy >/= 28 days (42 days for nitrosoureas or mitomycin C) prior to registration and have recovered from adverse events due to agents administered more than 28 days earlier.

5) Patients may have received prior monoclonal antibody therapy directed against VEGF, VEGFRI or VEFGR2.

6) Patients may have received prior surgery (including cytoreductive surgery, if there is residual measurable disease). At least 28 days must have elapsed since the prior surgery (i.e., thoracotomy, laparotomy, or any major surgery, NOT including minor surgeries such as mediastinoscopy, thoracoscopy, or minor biopsies) and the patient has recovered from all associated toxicities.

7) Patients may have received prior radiotherapy, provided that at least 21 days have elapsed since the last treatment and the patient has recovered from all associated toxicities at the time of registration.

8) Patients must have a Zubrod Performance Status of 0 - 2.

9) Patients must have adequate hematologic function as documented by a WBC >/= 3,000/ul, an ANC >/= 1,500/ul and a platelet count >/= 100,000/ul obtained within 28 days prior to registration.

10) Patients must have adequate hepatic function as evidenced by serum bilirubin </= institutional upper limits of normal. SGOT (AST) or SGPT (ALT) must be </= 1.5 x the institutional upper limit of normal. These tests must be obtained within 28 days prior to registration

11) Patients must have a serum creatinine </= 1.5 x the institutional upper limit of normal (IULN) or a measured creatinine clearance >/= 50 mL/min. These tests must be obtained within 28 days prior to registration.

12) Patients must have systolic blood pressure </= 150 mmHg and diastolic blood pressure </= 100 mmHg. Patients on stable antihypertensive therapy are eligible if blood pressure is within this range. Patients enrolled at UTMDACC must have blood pressure to equal or less than 140mmHg/90mmHg.

13) Institutions must have received IRB approval of S9925 (the Lung Cancer Specimen Repository). Patients must be offered participation in S9925. With the patient's consent, blood, plasma and tissue will be submitted for testing via S9925. Patients must be registered separately to S9925 in order for institutions to receive credit for submission.

14) Patients must have an EKG performed and must not have a mean QTc > 470 msec (with Bazett's correction) or have a history of familial long QT syndrome. EKG must be obtained within 14 days prior to registration.

15) All patients must be tested for proteinuria. Patients with 0 -1+ proteinuria are eligible. Patients with greater than I+ proteinuria on two consecutive dipsticks taken no less than 1 week apart are not eligible. Initial testing must be done within 28 days prior to registration.

16) Patients must not have gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease. Patients must either be able to swallow and/or receive enteral medications via gastrostomy feeding tube.

17) Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

18) No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years.

19) All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

20) At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base.

21) Patients must have a New York Heart Association Classification of I or II. Patients with New York Heart Association Classification of Ior II must be controlled with treatment.

Exclusion Criteria:1) HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171.

2) Patients with known CNS metastases are not eligible.

3) Patients with intractable nausea or vomiting are not eligible.

4) Pregnant or nursing women may not participate in this trial because of the increased risk of fetal harm including fetal death from the chemotherapeutic agents.

5) Prior immunotherapy.

6) Prior treatment with a TKI against VEGFR1 and/or VEGFR2.

7) Conditions requiring concurrent use of drugs or biologics with proarrythmic potential.

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Links
Registration Number: NCT00243074
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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