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A Phase II/III Double Blind Randomized Trial of AZD2171 Versus Placebo in Patients Receiving Paclitaxel/Carboplatin Chemotherapy for the Treatment of Advanced or Metastatic Non-Small Cell Lung Cancer

Phase 2/Phase 3
18 Years
Not Enrolling
Lung Cancer

Thank you

Trial Information

A Phase II/III Double Blind Randomized Trial of AZD2171 Versus Placebo in Patients Receiving Paclitaxel/Carboplatin Chemotherapy for the Treatment of Advanced or Metastatic Non-Small Cell Lung Cancer



- Compare the progression-free survival of patients with stage IIIB or IV non-small cell
lung cancer treated with paclitaxel and carboplatin in combination with either
cediranib maleate or a placebo.

- Determine the pharmacogenomics and pharmacodynamic aspects of these regimens in these
patients. (Phase II)

- Compare the overall survival of patients treated with these regimens. (Phase III)


- Compare objective tumor response rates in patients treated with these regimens.

- Determine the time to response and response duration in patients treated with these
regimens. (Phase III)

- Determine the nature, severity, and frequency of the toxic effects of these regimens,
including hemorrhage and hemoptysis, in these patients.

- Correlate the expression of tissue markers (at diagnosis) with outcomes and response in
patients treated with these regimens. (Phase III)

- Compare quality of life of patients treated with these regimens. (Phase III)

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to gender, participating center, disease stage (IIIB vs IV), weight
loss (≥ 5% vs < 5%), and prior adjuvant chemotherapy (yes vs no). Patients are randomized to
1 of 2 treatment arms.

- Arm I: Patients receive oral cediranib maleate once daily in the absence of disease
progression or unacceptable toxicity. Patients also receive paclitaxel IV over 3 hours
and carboplatin IV over 30 minutes on day 1. Treatment with paclitaxel and carboplatin
repeats every 21 days for 6-8 courses in the absence of disease progression or
unacceptable toxicity.

- Arm II: Patients receive oral placebo once daily in the absence of disease progression
or unacceptable toxicity. Patients also receive paclitaxel and carboplatin as in arm I.

Quality of life is assessed at baseline, before each treatment course, after completion of
study treatment, and every 3 months thereafter.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 750 patients will be accrued for this study.

Inclusion Criteria


- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), meeting
1 of the following stage criteria:

- Stage IIIB disease

- Patients without pleural effusion who are not candidates for combined
modality treatment OR who were treated at centers where combined modality
treatment is not considered standard treatment are eligible

- Stage IV disease

- Measurable disease (phase II)

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
x-ray, ultrasound, physical exam, or conventional CT scan OR ≥ 10 mm by spiral
CT scan

- Measurable lesions must be outside a previous radiotherapy field if they are the
sole site of disease, unless disease progression has been documented

- No significant central thoracic lesion with any appreciable cavitation

- Measurable or nonmeasurable disease (phase III)

- No necrotic or hemorrhagic tumor or metastases

- No untreated brain or meningeal metastases

- CT scans are not required to rule out disease unless there is clinical suspicion
of CNS disease

- Patients with previously treated stable brain metastases (by radiography or
clinical exam) are eligible provided they are asymptomatic and do not require


Performance status

- ECOG 0-1

Life expectancy

- Not specified


- Absolute granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- No overt bleeding (i.e., ≥ 30 mL/episode) within the past 3 months


- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT ≤ 2 times ULN (< 5 times ULN if liver metastases are present)


- Creatinine clearance ≥ 50 mL/min

- Proteinuria ≤ grade 1


- Mean QTc ≤ 470 msec (with Bazett's correction) by ECG

- No unstable angina

- No congestive heart failure

- No myocardial infarction within the past year

- No cardiac ventricular arrhythmias requiring medication

- No history of 2nd- or 3rd-degree atrioventricular conduction defects

- No untreated or uncontrolled cardiovascular condition

- No symptomatic cardiac dysfunction

- No uncontrolled hypertension (i.e., resting blood pressure ≥ 150/100 mm Hg despite
antihypertensive therapy)

- No history of labile hypertension

- No history of poor compliance with antihypertensive medication

- No history of familial long-QT syndrome


- No clinically relevant hemoptysis (i.e., ≥ 5 mL fresh blood) within the past 4 weeks

- Flecks of blood only in sputum allowed


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective (double method for females; barrier method for
males) contraception

- Able and willing to participate in the quality of life assessment

- No peripheral neuropathy > grade 1

- No prior allergic reaction to drugs containing Cremophor EL®

- No active or uncontrolled infection

- No serious illness or medical condition which would preclude study compliance

- No inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis)

- No other malignancy within the past 5 years except basal cell or squamous cell skin
cancer or in situ cancer


Biologic therapy

- At least 14 days since prior epidermal growth factor receptor-inhibitor therapy
(e.g., tyrosine kinase inhibitor, monoclonal antibodies, vaccines, or other agents)

- No prior antiangiogenesis therapy, including any of the following:

- Bevacizumab

- Cediranib maleate

- AZD6474

- PTK787/ZK222584 (PTK/ZK)

- Sunitinib malate

- Concurrent epoetin alfa allowed


- At least 12 months since prior adjuvant chemotherapy

- Combined chemotherapy and radiotherapy regimens for locally advanced stage IIIB
disease is not considered adjuvant therapy and is not allowed

- No prior chemotherapy for metastatic or recurrent NSCLC

Endocrine therapy

- See Disease Characteristics

- At least 1 week since prior steroids


- See Disease Characteristics

- At least 21 days since prior radiotherapy except for low-dose non-myelosuppressive
radiotherapy with approval

- Concurrent palliative radiotherapy allowed with approval


- At least 14 days since prior major surgery


- Recovered from prior therapy

- Prior treatment with cyclooxygenase-2 inhibitors allowed

- Concurrent prophylactic anticoagulation (e.g., warfarin) allowed provided
requirements for INR are met

- No potent inhibitors of CYP3A4 and 2C8, including any of the following drugs:

- Amiodarone hydrochloride

- Clarithromycin

- Citalopram hydrobromide

- Erythromycin

- Omeprazole

- Simvastatin

- Atorvastatin

- Lovastatin

- Montelukast sodium

- Verapamil hydrochloride

- Ketoconazole

- Miconazole

- Indinovir and other antivrails

- Diltiazem

- No other concurrent experimental drug or anticancer therapy

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Glenwood D. Goss, MD, BCh, FCP, FRCPC

Investigator Role:

Study Chair

Investigator Affiliation:

Ottawa Regional Cancer Centre


Canada: Health Canada

Study ID:




Start Date:

September 2005

Completion Date:

January 2013

Related Keywords:

  • Lung Cancer
  • stage IIIB non-small cell lung cancer
  • stage IV non-small cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms