Efficacy Study Comparing ZD6474 in Combination With Pemetrexed and Pemetrexed Alone in 2nd Line NSCLC Patients
Condition: Non Small Cell Lung Cancer; Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Vandetanib; Pemetrexed
Intervention description: oral once daily tablet; intravenous infusion
Intervention MeSH terms: Pemetrexed
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 698.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NSCLC; Non Small Cell Lung Cancer

Summary:

      Non-small cell lung cancer (NSCLC) can be treated with drugs that kill tumour cells, stop
      them from dividing, or stop the growth of the blood supply that cancers need to grow and
      spread. Clinical research has shown that drugs that inhibit vascular endothelial growth
      factor receptor (VEGFR) or epidermal growth factor receptor (EGFR) signalling can increase
      overall survival in patients with advanced non-small cell lung cancer (NSCLC). Preclinical
      studies have shown that vandetanib (ZD6474) is an inhibitor of both VEGFR and EGFR
      signalling. Giving vandetanib may therefore inhibit the growth of cancer cells by blocking
      their blood supply and by stopping them from dividing. This lung cancer study is to
      investigate if adding vandetanib to Alimta (pemetrexed) is more effective than Alimta
      (pemetrexed) alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provision of informed consent

          -  Female or male aged 18 years or above

          -  Histologic or cytologic confirmation of locally advanced or metastatic NSCLC (stage
             IIIB or IV) on entry into study

          -  Failure of 1st line anti-cancer therapy (either radiological documentation of disease
             progression or due to toxicity) or subsequent relapse of disease following 1st line
             therapy

          -  WHO Performance status 0 - 2

          -  One or more measurable lesions at least 10 mm in the longest diameter (LD) by spiral
             CT scan or 20 mm with conventional techniques according to RECIST criteria. Previously
             irradiated lesions will not be considered measurable.

          -  Life expectancy of 12 weeks or longer

          -  Negative pregnancy test for women of childbearing potential only

        Exclusion Criteria:

          -  Mixed small cell and non-small cell lung cancer histology

          -  Patients have received 2nd-line or subsequent anti-cancer therapy

          -  Prior treatment with pemetrexed

          -  Prior treatment with VEGFR TKIs (previous treatment with bevacizumab [Avastin] is
             permitted)

          -  Known or suspected brain metastases or spinal cord compression, unless treated at
             least 4 weeks before entry, and stable without steroid treatment for 10 days

          -  The last radiation therapy within 4 weeks before the start of study therapy, not
             including local palliative radiation

          -  The last dose of prior chemotherapy or other anti-cancer therapy is discontinued less
             than 3 weeks before the start of study therapy (6 weeks for nitrosoureas, mitomycin,
             and suramin)

          -  Major surgery within 4 weeks before entry, or incompletely healed surgical incision

          -  Neutrophils <1.5 x 109/L or platelets <100 x 109/L

          -  Serum bilirubin >1.5 x the upper limit of reference range (ULRR)

          -  Creatinine clearance <50 ml/min calculated by either Cockcroft -Gault, 24 hours urine
             collection, EDTA scan or other validated methods

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 x ULRR in the
             absence of liver metastases, or > 5 x ULRR in the presence of liver metastases

          -  Alkaline phosphatase (ALP) >2.5 x ULRR in the absence of liver metastases, or >5 x
             ULRR in the presence of liver metastases

          -  Current active gastrointestinal disease that may affect the ability of the patient to
             absorb ZD6474 or tolerate diarrhoea

          -  Evidence of severe or uncontrolled systemic disease or any concurrent condition 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

          -  Any unresolved toxicity greater than CTCAE Grade 2 from previous anti-cancer therapy

          -  Significant cardiovascular event (e.g., myocardial infarction, superior vena cava
             [SVC] syndrome), New York Heart Association [NYHA] classification of heart disease ≥2
             within 3 months before entry, or presence of cardiac disease that in the opinion of
             the Investigator increases the risk of ventricular arrhythmia

          -  History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy,
             trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is
             symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained
             ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded

          -  Congenital long QT syndrome or 1st degree relative with unexplained sudden death under
             40 years of age

          -  QT prolongation with other medications that required discontinuation of that
             medication

          -  Presence of left bundle branch block (LBBB)

          -  QTc with Bazett's correction unmeasurable or ≥ 480 msec on screening ECG (Note: If a
             patient has QTc interval ≥480 msec on screening ECG, the screen ECG may be repeated
             twice [at least 24 hours apart]. The average QTc from the three screening ECGs must be
             <480 msec in order for the patient to be eligible for the study) Patients who are
             receiving a drug that has a risk of QTc prolongation are eligible if QTc is <460 msec.

          -  Potassium <4.0 mmol/L despite supplementation; serum calcium (or ionized or adjusted
             for albumin), or magnesium out of normal range despite supplementation

          -  Women who are pregnant or breast-feeding

          -  Any concomitant medications that may cause QTc prolongation or induce Torsades de
             Pointes or induce CYP3A4 function. Drugs that have a risk of QTc prolongation, that in
             the investigator's opinion cannot be discontinued, are allowed, but only of the QTc is
             <460 msec

          -  Hypertension not controlled by medical therapy (systolic blood pressure greater than
             160 millimetre of mercury [mmHg] or diastolic blood pressure greater than 100 mmHg)

          -  Previous or current malignancies of other histologies within the last 5 years, with
             the exception of in situ carcinoma of the cervix and adequately treated basal cell or
             squamous cell carcinoma of the skin

          -  Treatment with a non-approved or investigational drug within 30 days before Day 1 of
             study treatment

          -  Concomitant use of yellow fever vaccine or any live attenuated vaccines