Clinical trial NCT00459121: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: stage I non-small cell lung cancer
stage II non-small cell lung cancer
stage IIIA non-small cell lung cancer
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-04-11
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Complete Resection (R0) Rate
timeFrame: Following three cycles of pre-operative zactima and carboplatin/paclitaxel
Secondary outcomes:
measure: Post-Operative Mortality Rate
timeFrame: at 30 days
measure: Assess Toxicity of This Regimen and the Percentage of Patients Completing All Planned Cycles of Therapy
timeFrame: Weekly for the first cycle; Thereafter within 72 hours of each dose of carboplatin/paclitaxel
measure: Assess the Clinical Response Rate of the Proposed Pre-operative Regimen
timeFrame: End of three cycles of treatment
measure: Assess the Complete Pathologic Complete Response (CR) Rate With This Regimen.
timeFrame: 30 days post surgery
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Shirish M. Gadgeel, MD
role: STUDY_CHAIR
References: