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

Phase 3
18 Years
Open (Enrolling)
Lung Cancer

Thank you

Trial Information

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



- To compare overall survival of patients with stage IIIB-IV non-small cell lung cancer
treated with cediranib vs placebo administered in combination with paclitaxel and


- To compare the progression-free survival of patients treated with these regimens.

- To compare the objective response rates in patients treated with these regimens.

- To estimate time to response and response duration in patients treated with these

- To evaluate the nature, severity, and frequency of toxicities, including hemorrhage and
hemoptysis, in patients treated with these regimens.

- To compare the pharmacokinetics of paclitaxel between the two arms in a subset of
enrolled patients

- To compare the quality of life of patients treated with these regimens.

- To determine the incremental cost effectiveness and cost utility ratios for these

- To correlate the expression of tissue markers (at diagnosis) with outcomes and response
in an exploratory fashion OUTLINE: This is a multicenter study. Patients are stratified
by gender, center, disease stage (IIIB vs IV), weight loss (< 5% vs 5-10% vs unknown),
and prior adjuvant chemotherapy (yes vs no). Patients are randomized to 1 of 2
treatment arms.

- Arm I: Patients receive oral cediranib once daily on days 1-21 and paclitaxel IV over 3
hours and carboplatin IV over 30 minutes on day 1.

- Arm II: Patients receive oral placebo once daily on days 1-21 and paclitaxel and
carboplatin as in arm I.

Treatment in both arms repeats every 21 days for 4 to 6 courses in the absence of disease
progression or unacceptable toxicity.

Quality of life is assessed at baseline, on day 1 of each course, and periodically

After completion of study therapy, patients are followed every 12 weeks.

Inclusion Criteria


- Histologically or cytologically* confirmed non-small cell carcinoma of the lung

- Stage IIIB or IV disease NOTE: *Diagnosis by sputum cytology alone allowed
provided it is confirmed by a second sputum specimen

- Measurable disease, defined as at least 1 measurable lesion > 20 mm by x-ray,
ultrasound, or physical exam or ≥ 10 mm (lymph nodes must be ≥ 15 mm in the short
axis) by spiral CT scan or physical exam (in the first 260 patients randomized**)

- Measurable lesions that are sole sites of disease must be outside a previous
radiotherapy field unless disease progression has been documented NOTE:
**Measurable or nonmeasurable disease allowed after the first 260 patients

- No appreciable cavitation in central thoracic lesions

- No untreated brain or meningeal metastases

- Patients with treated and radiologic or clinical evidence of stable brain
metastases, with no evidence of cavitation or hemorrhage in the brain lesion,
are eligible provided the metastases are asymptomatic and do not require

- No pleural effusion


- ECOG performance status 0-1

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

- Platelet count ≥ 100,000/mm^3

- Creatinine clearance > 50 mL/min

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT ≤ 2 times ULN (< 5 times ULN if due to liver metastasis)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double-method contraception (barrier method for

- No other malignancy within the past 5 years, except in situ cancer, basal cell or
squamous cell skin cancer, or malignancy cured by definitive prior therapy alone
(e.g., surgery) and continuously disease-free for at least 5 years

- Mean QTc with Bazett correction ≤ 480 msec in screening ECG (at least one value must
be ≤ 480 msec when measured automatically or manually corrected using Bazett's or
Fridericia's correction)

- No history of familial long QT syndrome

- No untreated and/or uncontrolled cardiovascular conditions and/or symptomatic cardiac
dysfunction including any of the following:

- Unstable angina

- Congestive heart failure

- Myocardial infarction within the past year

- Cardiac ventricular arrhythmias requiring medication

- History of second or third degree atrioventricular conduction defects

- LVEF > 50% in patients with significant cardiac history, even if controlled

- No resting BP consistently > 150 mm Hg systolic and/or > 100 mm Hg diastolic

- No poorly controlled hypertension

- No history of labile hypertension or poor compliance with anti-hypertensive

- No overt bleeding (> 30 mL bleeding/episode) from any site within the past 3 months

- No clinically relevant hemoptysis (> 5 mL fresh blood) within the past 4 weeks

- Flecks of blood in sputum allowed

- No active or uncontrolled infections, or serious illnesses or medical conditions
which would not permit the patient to be treated according to the study

- No prior allergic reactions to drugs containing Cremophor EL®

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

- No documented weight loss > 10% within the past 3 months

- Patients with weight loss 5-10% or whose weight loss status is unknown are
eligible provided serum albumin levels are ≥ 30 g/L

- No peripheral neuropathy > grade 1

- Must be fit for combined modality treatment

- Sufficiently fluent and willing to complete quality-of-life questionnaires


- See Disease Characteristics

- Recovered from all prior therapy

- No prior chemotherapy for metastatic or recurrent disease

- No prior anti-angiogenic therapy (e.g., bevacizumab, cediranib, AZD6474, PTK/ZK,
sunitinib malate, or other agents considered angiogenesis inhibitors by NCIC Clinical
Trials Group for any indication)

- Prior cox-2 inhibitors in standard doses allowed

- At least 12 months since prior adjuvant chemotherapy for completely resected disease

- Combined chemotherapy/radiotherapy regimens for locally advanced stage IIIB
disease not allowed

- At least 21 days since prior radiotherapy

- At least 21 days since prior cetuximab or other monoclonal antibodies

- At least 14 days since prior EGFR inhibitor therapy for adjuvant therapy or
metastatic disease (e.g., tyrosine kinase inhibitors, vaccines, or other agents
considered by NCIC CTG as acting on the EGFR pathway)

- At least 14 days since prior major surgery

- At least 1 week since prior corticosteroids

- No other concurrent experimental drugs, anticancer treatment, or investigational

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Time Frame:

at every visit throughout trial

Safety Issue:


Principal Investigator

Scott A. Laurie, MD, FRCPC

Investigator Role:

Study Chair

Investigator Affiliation:

Ottawa Regional Cancer Centre


Canada: Health Canada

Study ID:




Start Date:

November 2008

Completion Date:

September 2013

Related Keywords:

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