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
16 Years
N/A
Both
Lung Cancer
Trial Information
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
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment
Outcome Measure:
Progression-free survival
Safety Issue:
No
Principal Investigator
Andrew M. Arnold, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Margaret and Charles Juravinski Cancer Centre
Authority:
United States: Food and Drug Administration
Study ID:
D4200C00005
NCT ID:
NCT00066313
Start Date:
May 2003
Completion Date:
December 2006
Related Keywords:
- Lung Cancer
- extensive stage small cell lung cancer
- limited stage small cell lung cancer
- Lung Neoplasms
- Small Cell Lung Carcinoma
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