Vandetanib, Carboplatin, and Paclitaxel in Treating Patients With Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer That Can Be Removed by Surgery

Study Overview
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Brief Summary
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RATIONALE: Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vandetanib together with chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well giving vandetanib together with carboplatin and paclitaxel works in treating patients with stage I, stage II, or stage III non-small cell lung cancer that can be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the feasibility of neoadjuvant vandetanib in combination with carboplatin and paclitaxel in patients with resectable stage IB, II, or IIIA non-small cell lung cancer. Secondary Assess the 30-day postoperative mortality rate in these patients. Assess the toxicity of this regimen in these patients. Determine the percentage of patients who complete all planned courses of therapy. Assess the clinical response rate in patients treated with this regimen. Assess the pathologic complete response rate in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive oral vandetanib once daily on days 1-21. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 3 courses. Patients undergo surgery at least 3 weeks after the last course of chemotherapy. PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

Official Title
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Assessment of Feasibility and Safety of the Addition of ZD6474 (Zactima) to Carboplatin and Paclitaxel Administered Neo-Adjuvantly in Stage IB, II and T3, N1 Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: paclitaxel
* Drug: Zactima
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), meeting 1 of the following staging criteria: Stage IB or II disease T3, N0-1 disease (stage IIIA) Deemed a surgical candidate No prior lung cancer (NSCLC or small cell lung cancer) PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% WBC ≥ 3,000/mm³ Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Bilirubin normal AST and ALT ≤ 2.5 times upper limit of normal (ULN) Creatinine ≤ 1.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No evidence of severe or uncontrolled systemic disease or any concurrent condition that, in the opinion of the investigator, would preclude study compliance No peripheral neuropathy ≥ grade 2 No hemoptysis within the past 12 weeks No spontaneous bleeding within the past 12 weeks No clinically significant cardiac event (e.g., NYHA class II-IV heart disease, myocardial infarction) within the past 3 months No history of asymptomatic sustained ventricular tachycardia or arrhythmia that is symptomatic or requires treatment, including any of the following: Multifocal premature ventricular contractions Bigeminy Trigeminy Ventricular tachycardia Uncontrolled atrial fibrillation Atrial fibrillation controlled with medication allowed No history of QTc prolongation as a result from other medication that required discontinuation of that medication No congenital long QT syndrome or first-degree family relative with an unexplained death before the age of 40 No left bundle branch block No QTc with Bazett's correction that is unmeasurable or QTc ≥ 480 milliseconds on screening ECG Patients with QTc ≥ 480 milliseconds on screening ECG may have ECG repeated twice Average QTc from the 3 screening ECG's must be < 480 milliseconds No uncontrolled hypertension (systolic BP > 160 mm Hg or diastolic BP > 100 mm Hg) No active diarrhea or active gastrointestinal disease that may affect the absorption of study drugs or ability to tolerate study drugs No other malignancy within the past 3 years except in situ cervical carcinoma or adequately treated basal cell or squamous cell carcinoma of the skin PRIOR CONCURRENT THERAPY: More than 4 weeks since major surgery and recovered No prior carboplatin, paclitaxel, or vandetanib More than 30 days since prior investigational agents More than 2 weeks since prior and no concurrent drugs that induce CYP3A4 including, but not limited to, any of the following: Rifampin Phenytoin Carbamazepine Barbiturates Hypericum perforatum (St. John's wort) No medication that may cause QTc prolongation or induce torsades de pointes for 2 weeks prior to beginning study treatment, during, and for 2 weeks after completion of study treatment No concurrent combination antiretroviral treatment for HIV-positive patients No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zactima, Paclitaxel, Carboplatin<br>Zactima- 100 mg orally daily, starting on day 1 of cycle 1. Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1. Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1 Duration of each cycle: 21 days. The last dose of zactima will be on the first day of the last cycle. Neoadjuvant Surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment. | Drug: carboplatin<br>* Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1<br>* Other names: Paraplatin ®;Drug: paclitaxel<br>* Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1.<br>* Other names: Onxal TM;Drug: Zactima<br>* Zactima- 100 mg orally daily, starting on day 1 of cycle 1.<br>* Other names: Vandetanib;Procedure: neoadjuvant therapy<br>* Neoadjuvant surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment.<br>* Other names: R0 Resection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Resection (R0) Rate |  | Following three cycles of pre-operative zactima and carboplatin/paclitaxel | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-Operative Mortality Rate |  | at 30 days | 
| Assess Toxicity of This Regimen and the Percentage of Patients Completing All Planned Cycles of Therapy | Serum chemistry includes Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, potassium, total protein, SGOT [AST], SGPT [ALT], sodium, laboratory tests should be done on a weekly basis for the first cycle. After the first cycle laboratory tests should be done within 72 hours of each dose of carboplatin/paclitaxel. | Weekly for the first cycle; Thereafter within 72 hours of each dose of carboplatin/paclitaxel | 
| Assess the Clinical Response Rate of the Proposed Pre-operative Regimen | Patients will undergo tumor evaluation when all of the three cycles have been completed unless the treating physician has concerns regarding tumor progression. If the patient has undergone tumor evaluation prior to the last cycle the patient will require repeat tumor assessment within 4 weeks of completion of the last cycle of therapy | End of three cycles of treatment | 
| Assess the Complete Pathologic Complete Response (CR) Rate With This Regimen. | Evaluation of the number of patients who have no evidence of tumor in the resected tumor. | 30 days post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I non-small cell lung cancer, stage II non-small cell lung cancer, stage IIIA non-small cell lung cancer