ZD6474 in Treating Patients With Small Cell Lung Cancer

NCT ID: NCT00066313

Last Updated: 2016-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-05-31
• Study Completion Date: 2006-12-31

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.

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.

Conditions

Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

vandetanib

Intervention Type: DRUG

adjuvant therapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, Canada

Cross Cancer Institute at University of Alberta

Edmonton, Alberta, Canada

British Columbia Cancer Agency - Centre for the Southern Interior

Kelowna, British Columbia, Canada

Fraser/Valley Cancer Centre at British Columbia Cancer Agency

Surrey, British Columbia, Canada

British Columbia Cancer Agency - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Moncton Hospital

Moncton, New Brunswick, Canada

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Margaret and Charles Juravinski Cancer Centre

Hamilton, Ontario, Canada

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, Canada

St. Catharines General Hospital at Niagara Health System

St. Catharines, Ontario, Canada

Northwestern Ontario Regional Cancer Care at Thunder Bay Regional Health Sciences Centre

Thunder Bay, Ontario, Canada

Toronto East General Hospital

Toronto, Ontario, Canada

Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre

Toronto, Ontario, Canada

Mount Sinai Hospital - Toronto

Toronto, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Windsor Regional Cancer Centre at Windsor Regional Hospital

Windsor, Ontario, Canada

Hopital Notre- Dame du CHUM

Montreal, Quebec, Canada

McGill Cancer Centre at McGill University

Montreal, Quebec, Canada

L'Hopital Laval

Ste-Foy, Quebec, Canada

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Countries

Canada

References

Arnold AM, Seymour L, Smylie M, Ding K, Ung Y, Findlay B, Lee CW, Djurfeldt M, Whitehead M, Ellis P, Goss G, Chan A, Meharchand J, Alam Y, Gregg R, Butts C, Langmuir P, Shepherd F; National Cancer Institute of Canada Clinical Trials Group Study BR.20. Phase II study of vandetanib or placebo in small-cell lung cancer patients after complete or partial response to induction chemotherapy with or without radiation therapy: National Cancer Institute of Canada Clinical Trials Group Study BR.20. J Clin Oncol. 2007 Sep 20;25(27):4278-84. doi: 10.1200/JCO.2007.12.3083.

Reference Type: RESULT

PMID: 17878480 (View on PubMed)

Other Identifiers

CAN-NCIC-BR20

Identifier Type: -

Identifier Source: secondary_id

ZENECA-6474IL/0005

Identifier Type: -

Identifier Source: secondary_id

CDR0000315518

Identifier Type: OTHER

Identifier Source: secondary_id

D4200C00005

Identifier Type: -

Identifier Source: org_study_id