Know Cancer

forgot password

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

Phase 2
16 Years
Not Enrolling
Lung Cancer

Thank you

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


- 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

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this

Inclusion Criteria


- 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



- Over 16

Performance status

- ECOG 0-2

Life expectancy

- At least 12 weeks


- Absolute granulocyte count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- No history of bleeding diathesis


- Bilirubin less than 1.5 times upper limit of normal (ULN)

- ALT less than 2.5 times ULN


- Creatinine less than 1.5 times ULN

- Calcium normal


- 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

- 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


- 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

- Willing and able to complete quality of life questionnaires in English or French


Biologic therapy

- No prior signal transduction inhibitors

- No prior angiogenesis inhibitors

- No concurrent anticancer biologic therapy or immunotherapy


- See Disease Characteristics

- Recovered from prior chemotherapy

Endocrine therapy

- Not specified


- See Disease Characteristics

- Recovered from prior radiotherapy

- No concurrent anticancer radiotherapy

- Concurrent low-dose, nonmyelosuppressive palliative radiotherapy allowed


- More than 2 weeks since prior major surgery


- 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

- No concurrent oral bisphosphonates (e.g., clodronate)

- Concurrent IV bisphosphonates allowed

- No concurrent 5HT_3 antagonists

Type of Study:


Study Design:

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Safety Issue:


Principal Investigator

Andrew M. Arnold, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Margaret and Charles Juravinski Cancer Centre


United States: Food and Drug Administration

Study ID:




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