Lung Cancer
Conditions
Keywords
stage I non-small cell lung cancer, stage II non-small cell lung cancer, stage IIIA non-small cell lung cancer
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.
Interventions
DRUGcarboplatin
Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1
DRUGpaclitaxel
Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1.
DRUGZactima
Zactima- 100 mg orally daily, starting on day 1 of cycle 1.
PROCEDUREneoadjuvant therapy
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.
Sponsors
National Cancer Institute (NCI)
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete Resection (R0) Rate | Following three cycles of pre-operative zactima and carboplatin/paclitaxel |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-Operative Mortality Rate | at 30 days | — |
| Assess Toxicity of This Regimen and the Percentage of Patients Completing All Planned Cycles of Therapy | Weekly for the first cycle; Thereafter within 72 hours of each dose of carboplatin/paclitaxel | 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. |
| Assess the Clinical Response Rate of the Proposed Pre-operative Regimen | End of three cycles of treatment | 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 |
| Assess the Complete Pathologic Complete Response (CR) Rate With This Regimen. | 30 days post surgery | Evaluation of the number of patients who have no evidence of tumor in the resected tumor. |
Countries
United States
Participant flow
Recruitment details
Unable to enroll patients in a timely fashion. The decision was made to close the study after consulting with AstraZeneca.
Pre-assignment details
Feasibility and safety.
Participants by arm
| Arm | Count |
|---|---|
| Zactima, Paclitaxel, Carboplatin 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. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Zactima, Paclitaxel, Carboplatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 56.5 years STANDARD_DEVIATION 0 |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Complete Resection (R0) Rate
Time frame: Following three cycles of pre-operative zactima and carboplatin/paclitaxel
Population: No analysis was completed only 2 patients enrolled, study closed due to slow accrual.
Secondary
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
Time frame: End of three cycles of treatment
Population: No analysis was completed only 2 patients enrolled, study closed due to slow accrual.
Secondary
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.
Time frame: 30 days post surgery
Population: No analysis was completed only 2 patients enrolled, study closed due to slow accrual.
Secondary
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.
Time frame: Weekly for the first cycle; Thereafter within 72 hours of each dose of carboplatin/paclitaxel
Population: No analysis was completed only 2 patients enrolled, study closed due to slow accrual.
Secondary
Post-Operative Mortality Rate
Time frame: at 30 days
Population: No analysis was completed only 2 patients enrolled, study closed due to slow accrual.