Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

ZD6474 and Docetaxel in Treating Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI, Pharmaceutical / Industry UCLA-0208009 ZENECA-6474IL/0006, NCT00054093

Objectives

1. 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.
2. Compare the tolerability and safety of these regimens, in terms of incidence and nature of adverse effects and electrocardiogram changes, in these patients.
3. Compare the objective response rate and duration of response of patients treated with these regimens.
4. Compare the pharmacokinetics of these regimens in these patients.
5. Compare the overall survival of patients treated with these regimens.
6. Compare objective tumor response and progression-free survival with the biological assessment of these regimens in these patients.
7. Compare quality of life, lung cancer symptoms, and performance status of patients treated with these regimens.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• WHO 0-1

Life expectancy

• At least 12 weeks

Hematopoietic

• Neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

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/m²)

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

Expected Enrollment

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).

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.

Heymach JV, Johnson BE, Prager D, et al.: Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non small-cell lung cancer. J Clin Oncol 25 (27): 4270-7, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Diane Prager, MD, Principal investigator(Contact information may not be current)		Ph: 310-825-5268; 888-798-0719

Registry Information
Official Title		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
Trial Start Date		2002-11-26
Registered in ClinicalTrials.gov		NCT00054093
Date Submitted to PDQ		2002-12-17
Information Last Verified		2004-08-19
NCI Grant/Contract Number		P30-CA16042

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