ZD6474 in Treating Patients With Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: ZD6474 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. ZD6474 may also stop the growth of small cell lung cancer by blocking blood flow to the tumor. PURPOSE: This randomized phase II trial is studying how well ZD6474 works compared to placebo in treating patients with small cell lung cancer that has responded to previous chemotherapy with or without radiation therapy.

Detailed Description
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OBJECTIVES: Compare the progression-free survival of patients with previously treated small cell lung cancer (SCLC) treated with ZD6474 vs placebo. Compare the response rate of patients treated with these regimens (only patients who had measurable disease outside a prior radiation field at study entry). Compare the toxicity and tolerability of these regimens in these patients. Compare the pharmacokinetics of these regimens in these patients. Correlate outcome and response with vascular endothelial growth factor expression and microvessel density in patients treated with these regimens. Compare the quality of life of patients treated with these regimens. Provide a comprehensive tumor, plasma, and urine bank linked to a clinical database for further study of molecular markers in SCLC. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center, timing of prior radiotherapy (early [before day 1, course 4 of chemotherapy] vs late vs no prior radiotherapy), stage of disease at diagnosis (limited vs extensive), and response at study entry (complete vs partial). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral ZD6474 daily. Arm II: Patients receive oral placebo daily. In both arms, courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, every 4 weeks while on therapy, and then every 8 weeks until disease progression. Patients are followed every 8 weeks until disease progression and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

Official Title
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A Phase II Study Of ZD6474 Or Placebo In Small Cell Lung Cancer Patients Who Have Complete Or Partial Response To Induction Chemotherapy +/- Radiation Therapy

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: vandetanib
* Procedure: adjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed small cell carcinoma of the lung Small cell and variant histology allowed No mixed tumors (small and large cell) No neuroendocrine tumors of the lung Must have received at least 4 courses of first-line combination chemotherapy as part of an induction regimen No prior change in regimen due to disease progression Must have achieved a radiologically confirmed (i.e., CT scan, chest x-ray, or bone scan) complete response (CR) or partial response (PR) after prior chemotherapy with or without radiotherapy AND meets 1 of the following criteria: No more than 28 days since prior chemotherapy At least 7 and no more than 14 days since prior radiotherapy if administered after completion of prior chemotherapy* No CNS metastases Asymptomatic patients with CNS metastases who received prior therapeutic cranial irradiation and are on stable, decreasing, or no steroids are eligible No symptomatic lesions or evidence of necrosis or bleeding NOTE: *Randomization may take place up to 21 days after prior radiotherapy in the instance of severe esophagitis that precludes administration of oral medications PATIENT CHARACTERISTICS: Age Over 16 Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 No history of bleeding diathesis Hepatic Bilirubin less than 1.5 times upper limit of normal (ULN) ALT less than 2.5 times ULN Renal Creatinine less than 1.5 times ULN Calcium normal Cardiovascular No prior ventricular arrhythmia that was symptomatic or required treatment (CTC grade 3), including any of the following: Multifocal premature ventricular contractions Bigeminy Trigeminy Ventricular tachycardia No prior QT prolongation with any medication No congenital long QT syndrome No QT and QTc (with Bazett's correction) that is unmeasurable or is 460 msec or higher on screening ECG No significant cardiac event, including symptomatic heart failure or angina, within the past 3 months or any cardiac disease that increases the risk for ventricular arrhythmia No ongoing chronic atrial fibrillation LVEF at least 45% by MUGA for patients with significant cardiac history (myocardial infarction, severe hypertension, or arrhythmia) OR who received prior doxorubicin greater than 450 mg/m^2 Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Potassium normal Magnesium normal No serious active infection No recent major bleeding No other concurrent serious underlying medical condition that would preclude study participation Willing and able to complete quality of life questionnaires in English or French PRIOR CONCURRENT THERAPY: Biologic therapy No prior signal transduction inhibitors No prior angiogenesis inhibitors No concurrent anticancer biologic therapy or immunotherapy Chemotherapy See Disease Characteristics Recovered from prior chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics Recovered from prior radiotherapy No concurrent anticancer radiotherapy Concurrent low-dose, nonmyelosuppressive palliative radiotherapy allowed Surgery More than 2 weeks since prior major surgery Other More than 4 weeks since prior investigational drugs No prior epidermal growth factor receptor inhibitors No prior vascular endothelial growth factor receptor inhibitors No concurrent CYP3A4 inhibitors or inducers, including any of the following: Verapamil Rifampin Phenytoin Carbamazepine Barbiturates Hypericum perforatum (St. John's wort) No concurrent medication that affects QT/QTc and/or induces torsades de pointes No other concurrent anticancer cytotoxic therapy No other concurrent investigational drugs during and for 30 days after study participation No concurrent oral bisphosphonates (e.g., clodronate) Concurrent IV bisphosphonates allowed No concurrent 5HT_3 antagonists

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: vandetanib|nan|
|Procedure: adjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  |  | 
| Response rates |  |  | 
| Toxicity and safety |  |  | 
| Pharmacokinetics |  |  | 
| Quality of life (QOL) as measured by EORTC QLQ-C30 and QLQ-LC13 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extensive stage small cell lung cancer, limited stage small cell lung cancer