A Study To Assess ZD6474 (ZACTIMA™) Monotherapy In Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer

Thyroid Cancer Clinical Trial

Official title:

A Phase II, Open-Label Study To Assess The Efficacy and Tolerability of ZD6474 (ZACTIMA™ ) 100 mg Monotherapy In Subjects With Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00358956
• Other study ID #: D4200C00068
• Status: Completed
• Phase: Phase 2
• First received: July 28, 2006
• Last updated: February 10, 2015
• Start date: August 2006
• Est. completion date: May 2014

Study information

• Verified date: February 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationCanada: Health CanadaSpain: Spanish Agency of MedicinesSwitzerland: SwissmedicItaly: The Italian Medicines AgencyRomania: National Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

This will be a Phase II, open label study to establish the effect of once-daily oral doses of ZD6474 100mg in subjects with locally advanced or metastatic hereditary medullary thyroid cancer in whom no standard therapeutic option is available.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: May 2014
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Provision of written informed consent

• Previously confirmed histological diagnosis of locally advanced or metastatic hereditary medullary thyroid carcinoma without standard therapeutic options

• Aged 18 or over and a life expectancy of more than 12 weeks

Exclusion Criteria:

• The last dose of prior chemo/radiation received less than 4 weeks before the start of study therapy

• Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age, history of arrhythmia

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• ZD6474 (vandetanib)
100 mg once daily oral tablet

Locations

Country	Name	City	State
Australia	Research Site	St Leonards
Canada	Research Site	Sherbrooke	Quebec
Italy	Research Site	Pisa
Netherlands	Research Site	Utrecht
Romania	Research Site	Bucharest
Spain	Research Site	Madrid
Switzerland	Research Site	Basel
United States	Research Site	Boston	Massachusetts
United States	Research Site	Little Rock	Arkansas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Italy,  Netherlands,  Romania,  Spain,  Switzerland, 

References & Publications (1)

Robinson BG, Paz-Ares L, Krebs A, Vasselli J, Haddad R. Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Endocrinol Metab. 2010 Jun;95(6):2664-71. doi: 10.1210/jc.2009-2461. Epub 2010 Apr 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as defined by RECIST criteria.; The categories for best objective response are CR, PR, stable disease (SD)>= 12 weeks, progressive disease (PD) or NE.	RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment.	No
Secondary	Progression-Free Survival (PFS)	Median progression free survival (months) estimated from a Weibull model with corresponding 95% confidence intervals. Progression free survival is the time from randomisation until objective disease progression (determined by RECIST assessments) or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment.	RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment.	No
Secondary	Disease Control Rate (DCR)	Disease control rate is defined as the number of patients who achieved disease control at 8 weeks following randomisation. Disease control at 8 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 24 weeks	RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment.	No
Secondary	World Heath Organization (WHO) Performance Status	Number of patients demonstrating an improvement from baseline to 24 weeks in WHO PS. Where WHO PS is the standard scale with patients scored (0 healthy - 5 dead) based on their physical capabilities	WHO PS assessed at screening (up to 3 weeks prior to first dose), baseline and then every 12 weeks (± 2 weeks), up to and including discontinuation of study treatment.	No
Secondary	Symptomatic Response	Symptomatic response will be defined as at least a 50% decrease in the stool frequency (represented by a persistent decrease in stool frequency over 4 weeks), taking as reference the baseline (mean) level.	Symptomatic diarrhea was assessed using stool frequency diaries. Baseline was established using the average of the 4 days immediately prior to first dose, then weekly until discontinuation of study treatment.	No
Secondary	Biochemical Response Calcitonin (CTN )	A patient's best biochemical response was calculated from assessments performed at baseline and during treatment. Responders were those patients with a best biochemical response of CR or PR, confirmed by repeat assessments, which were to be performed no less than 4 weeks after the criteria for PR or CR were first met.	Blood samples for analysis of CTN were taken at screening (0, 1, 4, and 8 hours to determine the baseline CTN/CEA level) then every 4 weeks until discontinuation Time point(s) at which outcome measure was assessed. (Limit: 255 characters)	No
Secondary	Biochemical Response Carcinoembryonic Antigen CEA)	A patient's best biochemical response was calculated from assessments performed at baseline and during treatment. Responders were those patients with a best biochemical response of CR or PR, confirmed by repeat assessments, which were to be performed no less than 4 weeks after the criteria for Partial Response (PR) or Complete Response (CR) were first met.	Blood samples for analysis of CTN were taken at screening (0, 1, 4, and 8 hours to determine the baseline CTN/CEA level) then every 4 weeks until discontinuation	No

External Links

•   Link
•   AstraZeneca Clinical Trial Information - Outside US
•   CSR-D4200C00068.pdf