Cediranib, Paclitaxel, and Carboplatin in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: carboplatin; cediranib maleate; paclitaxel; placebo
Intervention description: Given IV; Given orally; Given IV; Given orally
Intervention MeSH terms: Paclitaxel; Carboplatin; Cediranib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 306.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer

Summary:

      RATIONALE: Cediranib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work
      in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing. It is not yet known whether cediranib is more effective than a
      placebo when given together with paclitaxel and carboplatin in treating patients with
      non-small cell lung cancer.

      PURPOSE: This randomized phase III trial is studying how well cediranib works when given
      together with paclitaxel and carboplatin in treating patients with stage IIIB or stage IV
      non-small cell lung cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  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
                  corticosteroids

          -  No pleural effusion

        PATIENT CHARACTERISTICS:

          -  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
             men)

          -  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 medication

          -  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

        PRIOR CONCURRENT THERAPY:

          -  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
             therapy