Trial of ZD6474 and Faslodex in Non-Small Cell Lung Cancer

Inclusion Criteria:

• Pathologically/histologically confirmed non-small cell lung cancer (NSCLC), advanced (stage IIIB w/ effusion or IV).
• Performance status of 0, 1, or 2
• Brain metastases must be clinically stable after treatment with surgery and/or radiotherapy
• Must have received two prior systemic anti-cancer regimens for recurrent/ metastatic disease, including one platinum-containing regimen
• Prior radiotherapy, chemotherapy and/or treatment with investigational agents is allowed provided that the patient has recovered from the treatment-related side effects to grade ≤1, and that at least 3 weeks has passed since the last dose
• Required laboratory values demonstrating adequate bone marrow, kidney, liver, and blood clotting function.
• Negative pregnancy test for women of childbearing potential within 7 days prior to study entry
• Life expectancy of 3 months or more
• Must tolerate intramuscular injections
• No prior or concurrent use of estrogen replacement therapy
• No concurrent use of cytotoxic, immunologic, hormonal, or investigational agent intended for the antitumor treatment of NSCLC

Exclusion Criteria:

• Prior therapy with any anti-EGFR therapy such as gefitinib (IRESSA), erlotinib (TARCEVA), vandetanib (ZD6474, ZACTIMA), or fulvestrant (FASLODEX), or an aromatase inhibitor
• Clinically significant cardiac event such as myocardial infarction, superior vena cava syndrome, New York Heart Association (NYHA) classification of heart disease ≥ 2 within 3 months before entry
• 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
• Presence of left bundle branch block
• Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age
• History of QTc prolongation as a result from other medications that required discontinuation of that medication
• QTc with Bazett's correction that is unmeasurable, or ≥ 480 msec on screening ECG
• Potassium <4.0 mmol/L despite supplementation, or potassium above the CTCAE grade 1 upper limit
• Serum calcium above the CTCAE grade 1 upper limit
• Magnesium below the normal range despite supplementation, or above the CTCAE grade 1 upper limit
• Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
• Diagnosis of active interstitial lung disease
• Currently active diarrhea that may affect drug absorption
• Previous or current malignancies of other histologies within the last 5 years, with the exception of cervical carcinoma in situ and basal cell or squamous cell carcinoma of the skin
• Concomitant use of medications that are potent inducers of CYP3A4 are not allowed within 2 weeks of study or during the study
• Any unresolved toxicity greater than CTC grade 1 from previous anti-cancer therapy
• Major surgery within 4 weeks, or incompletely healed surgical incision
• Women who are currently pregnant or breast feeding
• History of bleeding diathesis (ie, disseminated intravascular coagulation [DIC], clotting factor deficiency)
• History of hypersensitivity to active or inactive excipients of fulvestrant (ie castor oil or Mannitol)