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

Purpose

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.

Condition	Intervention	Phase
Thyroid Cancer	Drug: ZD6474 (vandetanib)	Phase 2

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Thyroid Cancer Thyroid Diseases

Drug Information available for: Thyroid Vandetanib

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Objective Response Rate (ORR) [ Time Frame: 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. ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Progression-Free Survival (PFS) [ Time Frame: 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. ] [ Designated as safety issue: No ]
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.
Disease Control Rate (DCR) [ Time Frame: 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. ] [ Designated as safety issue: No ]
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
World Heath Organization (WHO) Performance Status [ Time Frame: 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. ] [ Designated as safety issue: No ]
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
Symptomatic Response [ Time Frame: 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. ] [ Designated as safety issue: No ]
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.
Biochemical Response Calcitonin (CTN ) [ Time Frame: 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) ] [ Designated as safety issue: No ]
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.
Biochemical Response Carcinoembryonic Antigen CEA) [ Time Frame: 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 ] [ Designated as safety issue: No ]
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.

Enrollment:	19
Study Start Date:	August 2006
Estimated Study Completion Date:	December 2012
Primary Completion Date:	January 2008 (Final data collection date for primary outcome measure)

Intervention Details:

100 mg once daily oral tablet

Other Name: Caprelsa™

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00358956

Locations

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

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:

Peter Langmuir, MD

AstraZeneca

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00358956 History of Changes
Other Study ID Numbers:	D4200C00068
Study First Received:	July 28, 2006
Results First Received:	April 27, 2011
Last Updated:	October 3, 2012
Health Authority:	United States: Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration Canada: Health Canada Spain: Spanish Agency of Medicines Switzerland: Swissmedic Italy: The Italian Medicines Agency Romania: National Medicines Agency Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by AstraZeneca:

medullary thyroid cancer
MTC
hereditary medullary thyroid cancer
thyroid cancer

Additional relevant MeSH terms:

Thyroid Neoplasms
Thyroid Diseases
Endocrine Gland Neoplasms
Neoplasms by Site

Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases

ClinicalTrials.gov processed this record on June 18, 2013