ZD6474 in Treating Patients With Small Cell Lung Cancer

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00066313
• Other study ID #: D4200C00005
• Secondary ID: CAN-NCIC-BR20ZEN
• Status: Completed
• Phase: Phase 2
• First received: August 6, 2003
• Last updated: August 23, 2016
• Start date: May 2003
• Est. completion date: December 2006

Study information

• Verified date: August 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: December 2006
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 120 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• vandetanib

Procedure:
• adjuvant therapy

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Cross Cancer Institute at University of Alberta	Edmonton	Alberta
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	British Columbia Cancer Agency - Centre for the Southern Interior	Kelowna	British Columbia
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	Moncton Hospital	Moncton	New Brunswick
Canada	Hopital Notre- Dame du CHUM	Montreal	Quebec
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	St. Catharines General Hospital at Niagara Health System	St. Catharines	Ontario
Canada	L'Hopital Laval	Ste-Foy	Quebec
Canada	Fraser/Valley Cancer Centre at British Columbia Cancer Agency	Surrey	British Columbia
Canada	Northwestern Ontario Regional Cancer Care at Thunder Bay Regional Health Sciences Centre	Thunder Bay	Ontario
Canada	Mount Sinai Hospital - Toronto	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	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	British Columbia Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	Windsor Regional Cancer Centre at Windsor Regional Hospital	Windsor	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Country where clinical trial is conducted

Canada, 

References & Publications (2)

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. Pha — View Citation

Arnold AM, Smylie M, Ding K, et al.: Randomized phase II study of maintenance vandetanib (ZD6474) in small cell lung cancer (SCLC) patients who have a complete or partial response to induction therapy: NCIC CTG BR.20. [Abstract] J Clin Oncol 25 (Suppl 18)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival			No
Secondary	Overall Survival			No
Secondary	Response rates			No
Secondary	Toxicity and safety			Yes
Secondary	Pharmacokinetics			No
Secondary	Quality of life (QOL) as measured by EORTC QLQ-C30 and QLQ-LC13			No