An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer - Full Text View

Purpose

The purpose of this study is to learn how hereditary or sporadic medullary thyroid cancer patients, treated with ZD6474, react to the drug, what happens to ZD6474 in the human body, about the side effects of ZD6474, and if ZD6474 can decrease or prevent the growth of tumors.

Condition	Intervention	Phase
Thyroid Cancer	Drug: ZD6474 (Vandetanib)	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	An International, Phase III, Randomized, Double-Blinded, Placebo-Controlled, Multi-Center Study to Assess the Efficacy of ZD6474 (ZACTIMATM) Versus Placebo in Subjects With Unresectable Locally Advanced or Metastatic 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:

Progression-Free Survival(PFS) [ Time Frame: RECIST tumour assessments were performed at screening (within 3 weeks before date of randomisation), then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent. ] [ Designated as safety issue: No ]
Median time to progression (months) 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. Values here are estimated (from a Weibull model) as the medians were not met.

Secondary Outcome Measures:

Objective Response Rate (ORR) [ Time Frame: RECIST assessments performed at screening (within 3 weeks before randomisation), then every 12 weeks. For patients with objective response of CR or PR, an additional confirmatory scan was performed ≥4 weeks following the date of first response. ] [ 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.
Disease Control Rate (DCR) [ Time Frame: RECIST tumour assessments were performed at screening (within 3 weeks before date of randomisation), then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent ] [ 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) >= 12 weeks
Duration of Response (DoR) [ Time Frame: RECIST tumour assessments were performed at screening (within 3 weeks before date of randomisation), then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent ] [ Designated as safety issue: No ]
Response is defined as a confirmed best objective response of CR or PR. Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment). Values are estimated as the medians weren't met
Overall Survival (OS) [ Time Frame: Number of deaths since randomisation ] [ Designated as safety issue: No ]
As data was immature at data cut off, number of death events is quoted
Biochemical Response Calcitonin (CTN) [ Time Frame: Blood samples Blood samples for analysis of CTN were taken at screening baseline (average of 0, 1, 4 and 8 hours), then every 4 weeks until discontinuation and 60 day follow up ] [ Designated as safety issue: No ]
Best biochemical response was calculated from assessments 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. CR and PR being defined according to level of CTN.
Biochemical Response Carcinoembryonic Antigen (CEA) [ Time Frame: Blood samples for analysis of CEA were taken at screening baseline (average of 0, 1, 4 and 8 hours), then every 4 weeks until discontinuation and 60 day follow up ] [ Designated as safety issue: No ]
Best biochemical response was calculated from assessments 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. CR and PR being defined according to level of CEA.
Time to Worsening of Pain (TWP) [ Time Frame: During the last week of the screening period (Day -7 to Day 0), the brief pain inventory (BPI) and opioid analgesic use were self-reported once a day for 4 days to establish baseline, then every week during blinded study treatment, up to discontinuation. ] [ Designated as safety issue: No ]
TWP was derived using the worst pain score from brief pain inventory (BPI) and patient reported opioid analgesic use. BPI uses 0 to 10 numeric rating scales asking subjects to rate their pain.

Enrollment:	331
Study Start Date:	November 2006
Estimated Study Completion Date:	December 2016
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
No Intervention: 1 Placebo vandetanib
Experimental: 2 Vandetanib	Drug: ZD6474 (Vandetanib) once daily oral tablet Other Name: ZACTIMA™

Eligibility

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

Criteria

Inclusion Criteria:

Confirmed diagnosis of unresectable, locally advanced or metastatic hereditary or sporadic Medullary Thyroid Cancer.
Presence of measurable tumor
Able to swallow medication

Exclusion Criteria:

Major surgery within 4 weeks before randomization
Last dose of prior chemotherapy received less than 4 weeks prior to randomization
Radiation therapy within the last 4 weeks prior to randomization(with exception of palliative radiotherapy)
Brain metastases or spinal cord compression, unless treated at least 4 weeks before first dose and stable without steroid treatment for 10 days
Significant cardiac events
Previous ZD6474 treatment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00410761

Show 73 Study Locations

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:	Peter Langmuir, MD	AstraZeneca
Principal Investigator:	Samuel Wells, MD	Duke University

More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B, Vasselli JR, Read J, Langmuir P, Ryan AJ, Schlumberger MJ. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012 Jan 10;30(2):134-41. Epub 2011 Oct 24.

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00410761 History of Changes
Other Study ID Numbers:	D4200C00058
Study First Received:	December 6, 2006
Results First Received:	April 27, 2011
Last Updated:	February 22, 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) Germany: Federal Institute for Drugs and Medical Devices Mexico: Ministry of Health Portugal: National Pharmacy and Medicines Institute Sweden: Medical Products Agency Hungary: National Institute of Pharmacy France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Austria: Agency for Health and Food Safety Denmark: Danish Medicines Agency Poland: Ministry of Health Belgium: Directorate general for the protection of Public health: Medicines Korea: Food and Drug Administration China: Food and Drug Administration India: Ministry of Health Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Brazil: Ministry of Health

Keywords provided by AstraZeneca:

ZD6474
MTC
Hereditary Medullary Thyroid Cancer
Sporadic Medullary Thyroid Cancer
Medullary 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 May 16, 2013