A Randomized, Double-Blind, Multicenter, Phase II Study To Assess The Safety, Tolerability, And Efficacy Of ZD6474 In Combination With Docetaxel (TAXOTERE) In Subjects With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Failure Of Prior Platinum-Based Chemotherapy
18 Years
N/A
Both
Lung Cancer
Trial Information
A Randomized, Double-Blind, Multicenter, Phase II Study To Assess The Safety, Tolerability, And Efficacy Of ZD6474 In Combination With Docetaxel (TAXOTERE) In Subjects With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Failure Of Prior Platinum-Based Chemotherapy
OBJECTIVES:
- Compare the efficacy of ZD6474 and docetaxel vs docetaxel and placebo, in terms of
progression-free survival, in patients with locally advanced or metastatic non-small
cell lung cancer refractory to platinum-based chemotherapy.
- Compare the tolerability and safety of these regimens, in terms of incidence and nature
of adverse effects and electrocardiogram changes, in these patients.
- Compare the objective response rate and duration of response of patients treated with
these regimens.
- Compare the pharmacokinetics of these regimens in these patients.
- Compare the overall survival of patients treated with these regimens.
- Compare objective tumor response and progression-free survival with the biological
assessment of these regimens in these patients.
- Compare quality of life, lung cancer symptoms, and performance status of patients
treated with these regimens.
OUTLINE: This is a multicenter, two-phase study comprising an open-label phase followed by a
double-blind, randomized phase.
- Open-label phase: Patients receive docetaxel IV over 1 hour on day 1 and oral ZD6474
once daily beginning on day 2. Treatment repeats every 21 days for a maximum of 6
courses in the absence of disease progression or unacceptable toxicity.
- Randomized phase: Patients are randomized to 1 of 3 treatment arms.
- Arm I: Patients receive docetaxel IV over 1 hour on day 1 and oral ZD6474 once
daily beginning on day 1.
- Arm II: Patients receive docetaxel as in arm I and ZD6474 as in arm I but at a
higher dose.
- Arm III: Patients receive docetaxel as in arm I and oral placebo once daily
beginning on day 1.
In all arms, courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity.
Quality of life is assessed at baseline, after the first 4 courses, and then after every
other course thereafter.
Patients are followed at 30 days and then every 6 weeks thereafter.
PROJECTED ACCRUAL: A total of 129 patients (9 patients for the open-label phase, 120
patients [40 per treatment arm] for the randomized phase) will be accrued for this study
within approximately 8 months (3 months for the open-label phase, 5 months for the
randomized phase).
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed non-small cell lung cancer
- Locally advanced or metastatic disease (stage IB-IV)
- No mixed small cell histology
- No bronchoalveolar carcinoma
- Failed first-line platinum-based chemotherapy
- At least one unidimensionally measurable lesion
- At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
- No brain metastases or spinal cord compression unless treated at least 4 weeks before
study and stable without steroids for at least 1 week
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- WHO 0-1
Life expectancy
- At least 12 weeks
Hematopoietic
- Neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic
- Bilirubin no greater than upper limit of normal (ULN)
- AST and ALT no greater than 1.5 times ULN
- Alkaline phosphatase no greater than 2.5 times ULN
- No hepatitis B
Renal
- Creatinine no greater than 1.5 times ULN
- Calcium (adjusted for albumin) normal
Cardiovascular
- No significant cardiovascular disease
- No symptomatic heart failure or angina within the past 3 months
- No cardiac disease that increases risk of a ventricular arrhythmia
- No clinically significant arrhythmia (e.g., multifocal premature ventricular
contractions, bigeminy, trigeminy, or ventricular tachycardia) that is symptomatic or
requires treatment
- No symptomatic sustained ventricular tachycardia
- No chronic atrial fibrillation
- No history of QT prolongation with other medications
- No congenital long QT syndrome
- No QTc with Bazett's correction unmeasurable or more than 460 msec by screening
electrocardiogram
- LVEF at least 45% by MUGA (for patients with prior anthracycline therapy with total
dose greater than 450 mg/m^2)
Pulmonary
- Oxygen saturation at least 90% on room air
- No requirement for supplemental oxygen
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-barrier contraception
- No known hypersensitivity to drugs formulated with polysorbate 80
- HIV negative
- No severe or uncontrolled systemic disease
- Magnesium normal
- Potassium at least 4.0 meq/L
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 6 weeks since prior suramin
- No concurrent biological response modifiers (including cytokines)
Chemotherapy
- See Disease Characteristics
- Prior docetaxel or paclitaxel allowed
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
Endocrine therapy
- See Disease Characteristics
- No concurrent hormonal therapy for cancer
Radiotherapy
- No prior chest radiotherapy
- More than 4 weeks since other prior radiotherapy
- No concurrent radiotherapy
Surgery
- Not specified
Other
- No prior agents that block the endothelial growth factor (EGF) or vascular EGF
pathways
- More than 4 weeks since prior systemic anticancer therapy
- More than 4 weeks since prior investigational agents
- More than 2 weeks since prior, and no concurrent, treatment with any of the
following:
- Amiodarone
- Chlorpromazine
- Ketoconazole
- Itraconazole
- Troleandomycin
- Erythromycin
- Diltiazem
- Verapamil
- Phenytoin
- Carbamazepine
- Rifampin
- More than 4 weeks since prior barbiturates
- More than 2 weeks since prior therapeutic-dose warfarin
- No concurrent therapeutic-dose warfarin
- No concurrent barbiturates
- No concurrent medications known to affect QTc
- No concurrent medications known to prolong QT interval or induce Torsade de Pointes
- No other concurrent anticancer therapy
- No other concurrent cytotoxic therapy for cancer
- No other concurrent investigational agents
- Low dose-warfarin for catheter clot prophylaxis allowed
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Diane Prager, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
D4200C00006
NCT ID:
NCT00054093
Start Date:
November 2002
Completion Date:
December 2007
Related Keywords:
- Lung Cancer
- stage IIIB non-small cell lung cancer
- recurrent non-small cell lung cancer
- stage IIIA non-small cell lung cancer
- stage IV non-small cell lung cancer
- stage II non-small cell lung cancer
- stage I non-small cell lung cancer
- squamous cell lung cancer
- large cell lung cancer
- adenocarcinoma of the lung
- adenosquamous cell lung cancer
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
Name | Location |
|---|---|
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
