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ZD6474 in Treating Patients With Small Cell Lung Cancer

Sponsor
Genzyme, a Sanofi Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00066313
Collaborator
(none)
21
Locations
43
Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: ZD6474 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. ZD6474 may also stop the growth of small cell lung cancer by blocking blood flow to the tumor.

PURPOSE: This randomized phase II trial is studying how well ZD6474 works compared to placebo in treating patients with small cell lung cancer that has responded to previous chemotherapy with or without radiation therapy.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

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.

Study Design

Study Type:
Interventional
Allocation:
Randomized
Masking:
Double
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
May 1, 2003
Actual Primary Completion Date :
Dec 1, 2006
Actual Study Completion Date :
Dec 1, 2006

Outcome Measures

Primary Outcome Measures

  1. Progression-free survival []

Secondary Outcome Measures

  1. Overall Survival []

  2. Response rates []

  3. Toxicity and safety []

  4. Pharmacokinetics []

  5. Quality of life (QOL) as measured by EORTC QLQ-C30 and QLQ-LC13 []

Eligibility Criteria

Criteria

Ages Eligible for Study:
16 Years to 120 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Tom Baker Cancer Centre - Calgary Calgary Alberta Canada T2N 4N2
2 Cross Cancer Institute at University of Alberta Edmonton Alberta Canada T6G 1Z2
3 British Columbia Cancer Agency - Centre for the Southern Interior Kelowna British Columbia Canada V1Y 5L3
4 Fraser/Valley Cancer Centre at British Columbia Cancer Agency Surrey British Columbia Canada V3V 1Z2
5 British Columbia Cancer Agency - Vancouver Cancer Centre Vancouver British Columbia Canada V5Z 4E6
6 Moncton Hospital Moncton New Brunswick Canada E1C 6ZB
7 Saint John Regional Hospital Saint John New Brunswick Canada E2L 4L2
8 Margaret and Charles Juravinski Cancer Centre Hamilton Ontario Canada L8V 5C2
9 Cancer Centre of Southeastern Ontario at Kingston General Hospital Kingston Ontario Canada K7L 5P9
10 Ottawa Hospital Regional Cancer Centre - General Campus Ottawa Ontario Canada K1H 8L6
11 St. Catharines General Hospital at Niagara Health System St. Catharines Ontario Canada L2R 5K3
12 Northwestern Ontario Regional Cancer Care at Thunder Bay Regional Health Sciences Centre Thunder Bay Ontario Canada P7B 6V4
13 Toronto East General Hospital Toronto Ontario Canada M4C 3E7
14 Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre Toronto Ontario Canada M4N 3M5
15 Mount Sinai Hospital - Toronto Toronto Ontario Canada M5G 1X5
16 Princess Margaret Hospital Toronto Ontario Canada M5G 2M9
17 Windsor Regional Cancer Centre at Windsor Regional Hospital Windsor Ontario Canada N8W 2X3
18 Hopital Notre- Dame du CHUM Montreal Quebec Canada H2L 4M1
19 McGill Cancer Centre at McGill University Montreal Quebec Canada H2W 1S6
20 L'Hopital Laval Ste-Foy Quebec Canada G1V 4G5
21 Saskatoon Cancer Centre at the University of Saskatchewan Saskatoon Saskatchewan Canada S7N 4H4

Sponsors and Collaborators

  • Genzyme, a Sanofi Company

Investigators

  • Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00066313
Other Study ID Numbers:
  • D4200C00005
  • CAN-NCIC-BR20
  • ZENECA-6474IL/0005
  • CDR0000315518
First Posted:
Aug 7, 2003
Last Update Posted:
Aug 24, 2016
Last Verified:
Aug 1, 2016
Keywords provided by Genzyme, a Sanofi Company
extensive stage small cell lung cancer
limited stage small cell lung cancer
Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma

Study Results

No Results Posted as of Aug 24, 2016