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Study Summary
No. 2004-0844:.......Head And Neck; Lung......John Heymach......Thoracic and Head and Neck Med
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Study Summary Title
Study Summary
Number:
2004-0844
Study Title:An Exploratory, Open Label Study to Assess the Effects of AZD2171 on Tumors and Biomarkers in Patients with Previously Untreated or Recurrent Non-Small Cell Lung Cancer (NSCLC) or Patients with Metastatic or Recurrent Head and Neck Cancer
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Physician New Patient Referral
Name:John HeymachPatients 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:Head And Neck
Lung
Supported By:N/A
Phase of Study:Phase IIReturn
Visit:
Patients will visit the clinic weekly for the first 3 weeks. Patients who
continue on study treatment beyond 3 weeks will visit the clinic at 6 weeks and
then every 4 weeks thereafter until discontinuation of study treatment.
Treatment
Agents:
AZD2171Home Care:Patients will be given a supply of study medication to be taken at home.
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to examine the effects on tumors of
AZD2171 in the treatment of NSCLC or HNC. The safety and tolerability of
AZD2171 will also be studied. Researchers will study if the drug's effects on
the cancer can be predicted by other effects of the drug, such as blood
pressure changes, changes in blood vessels in the skin, or substances in the
blood and various tissues called "biomarkers."
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Study Objectives / Outcomes
Primary: The primary objective of the study is to explore the short term effects of AZD271 on tumours in patients with previously untreated or recurrent non-small cell lung cancer (NSCLC) and in patients with previously untreated or recurrent non-small cell lung cancer (NSCLC) and in patients with metastatic or recurrent head and neck cancer (HNC) by combined assessment of:

-detectable changes in tumor metabolic activity determined by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) tumor SUVmax after 3 wks of dosing
-biomarkers measured in serial tumour biopsy samples (VEGF signalling pathway and other angiogenesis pathways; and other related pathways, including downstream markers of activation)
-mean arterial pressure

Secondary: To evaluate the safety and tolerability of AZD2171 by assessment of adverse events, laboratory findings and vital signs.


Exploratory:
  • To assess the mode-of-action of AZD2171 on tumours in patients with previously untreated or recurrent NSCLC and in patients with metastatic or recurrent HNC by assessment of tumour vessels before and after 3 weeks of treatment.
  • To investigate the effects of AZD2171 on surrogate biomarkers in skin and blood by assessment of markers measured in serial skin biopsy samples, soluble markers of angiogenesis and activated endothelial cells, circulating endothelial cells and VEGF receptor 1 (Flt-1) expressing monocytes before and after 3 weeks of treatment.
  • To explore relationships amongst changes in maximum tumor standardised uptake value & surrogate biomarkers in tumors,skin & blood,assessed as described above
  • To examine the relationship between tumour concentrations of AZD2171 to plasma concentrations of AZD2171 (subject to obtaining sufficient quantity of tumor tissue).
  • To define the features of tumours and patients responding to or progressing on AZD2171
  • To explore variants in germline genes that may be related to PK, PD, efficacy, or safety profile of response to AZD2171
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Study Status Information
Study Activation / Registration Date:07/27/2005
IRB Review and Approval Date:03/16/2005
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Terminated
Projected Accrual:Total accrual for all sites will be 20 participants.
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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) Provision of written informed consent

2) Aged 18 years and older

3) Histologically- or cytologically- confirmed head and neck or non-small cell bronchogenic carcinoma: adenocarcinoma (excluding bronchoalveolar), squamous (with exclusion of large central tumours) large cell carcinoma or mixed (adenocarcinoma and squamous) or undifferentiated carcinoma

4) Patients with NSCLC must have unresectable stage IIIb or stage IV disease

5) At least one lesion amenable to tumour biopsy and >/=1cm diameter (in order to be measurable by FDG-PET scanning) and patient fit to undergo repeated tumour biopsies and other mandatory study procedures

6) Considered suitable for treatment of NSCLC with no prior biological, or immunological therapy for disease. Or considered suitable for treatment of metastatic or recurrent HNC, with no prior biological, or immunological therapy for disease

7) WHO performance status (PS) 0-2

8) Expected not to deteriorate due to delay in start of standard therapy

9) Ability to remain in the study for a minimum duration of the screening period plus 3 weeks of study treatment.

Exclusion Criteria:1) Have received more than 2 previous chemotherapy regimens for NSCLC or have received the last chemotherapy agent within 28 days of the first dose of AZD2171. Previous chemotherapy for HNC if received with 28 days of first dose of AZD2171. Radiotherapy for HNC or NSCLC is not permissible within 28 days prior to dosing. If possible, the tumor biopsy should be outside of the radiotherapy field.

2) Untreated unstable brain or meningeal metastases. Patients with radiological evidence of stable brain metastases are eligible providing that they are asymptomatic and either - do not require corticosteriods, or - have been treated with corticosteriods, with clinical and radiological evidence of brain metastases stabilisation at least 10 days after discontinuation of steriods.

3) Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count </= 1.5 x 10^9/L or platelet count </= 100 x 10^9/L or requiring regular blood transfusions to maintain Haemoglobin > 9 g/dl

4) Serum bilirubin >/=1.5 x ULRR

5) ALT or AST >/=2.5 x ULRR. If liver metastases are present, ALT or AST > 5 x ULRR

6) Serum creatinine >1.5 x ULRR or a creatinine clearance of </=50mL/min calculated by Crockroft-Gault

7) Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart, unless urinary protein < 1.5 g in a 24 hour period.

8) History of significant gastrointestinal impairment, as judged by the investigator, that would significantly affect the absorption of AZD2171, including the ability to swallow the tablet whole

9) Patients with a history of poorly controlled hypertension with resting blood pressure >150/100 in the presence or absence of a stable regimen of hypertensive therapy. Measurements will be made after the subject has been resting supine for a minimum of 5 minutes. Two or more reading should be taken at 2-minute intervals and average. If the first diastolic readings differ by more than 5mmHg, then an additional reading should be obtained and averaged.

10) Any evidence of severe or uncontrolled systemic diseases (eg, unstable or uncompensated respiratory, cardiac including clinically significant arrhythmias, hepatic or renal disease)

11) Mean QTc with Bazetts correction >470msec in screening ECG or history of familial long QT syndrome. ( as per FDA guideline E14)

12) Recent(<14 days) major surgery prior to entry into the study, or a surgical incision that is not fully healed

13) Treatment with an investigational drug within 30 days prior to the first dose of AZD2171.

14) Broncho alveolar carcinoma

15) Diabetes patients with type I insulin dependent diabetes or poorly controlled type II insulin dependant diabetes or a fasting blood glucose >10mmol/l as FDG-PET scanning is contra indicated in such patients. Patients with diabetes may or may not be well controlled and the presence of altered insulin or glucose levels can interfere with PET scanning and may result in a false negative test

16) Known hypersensitivity to AZD2171 or any of it's excipients

17) Any concurrent condition or laboratory finding which, in the investigator's opinion, makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol

18) Known infection with hepatitis B or C or HIV

19) Pregnant or breast feeding patients or patients of child bearing potential with a positive pregnancy test prior to receiving study medication

20) Significant haemorrhage (>30 mL/episode in the previous 3 months) or haemoptysis (>5mL in previous 4 weeks)

21) Presence of necrotic/haemorrhagic tumour or metastases

22) Concomitant anticoagulant therapy, except for administration of low-dose anticoagulants for maintenance of central venous access.

23) Unresolved toxicity >CTC grade 2 from previous anti-cancer therapy except alopecia

24) Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff as the study site)

25) Previous enrolment or randomisation of treatment in the present study.

26) Other concomitant anti-cancer therapy (including LHRH agonists) except steriods

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Links
Registration Number: NCT00243347
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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