Clinical trial NCT00410761: An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Thyroid Cancer
Keywords: ZD6474
MTC
Hereditary Medullary Thyroid Cancer
Sporadic Medullary Thyroid Cancer
Medullary Thyroid Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-12-13
Enrollment: 437
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Progression-Free Survival(PFS)
timeFrame: 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then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent.
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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.
measure: Disease Control Rate (DCR)
timeFrame: 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
measure: Duration of Response (DoR)
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: Number of deaths since randomisation
measure: Biochemical Response Calcitonin (CTN)
timeFrame: 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
measure: Biochemical Response Carcinoembryonic Antigen (CEA)
timeFrame: 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
measure: Time to Worsening of Pain (TWP)
timeFrame: 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.
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Investigational Site Number 3
state: Arkansas
city: Little Rock
country: United States
facility: University Arkansas Site Number : 3
state: Arkansas
city: San Francisco
country: United States
facility: Investigational Site Number 8
state: California
city: San Francisco
country: United States
facility: USCF / Mt Zion Medical Center Site Number : 8
state: California
city: Aurora
country: United States
facility: Investigational Site Number 9
state: Colorado
city: Aurora
country: United States
facility: University Of Colorado Health Sciences Center Site Number : 9
state: Colorado
city: New Haven
country: United States
facility: Investigational Site Number 11
state: Connecticut
city: New Haven
country: United States
facility: Yale University School Medicine Site Number : 11
state: Connecticut
city: Jacksonville
country: United States
facility: Investigational Site Number 15
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic- Site Number : 15
state: Florida
city: Chicago
country: United States
facility: Investigational Site Number 18
state: Illinois
city: Chicago
country: United States
facility: The University Of Chicago Site Number : 18
state: Illinois
city: Lexington
country: United States
facility: Investigational Site Number 17
state: Kentucky
city: Lexington
country: United States
facility: The University Of Kentucky Site Number : 17
state: Kentucky
city: Boston
country: United States
facility: Dana Farber Cancer Institute Site Number : 2
state: Massachusetts
city: Boston
country: United States
facility: Investigational Site Number 2
state: Massachusetts
city: Detroit
country: United States
facility: Investigational Site Number 7
state: Michigan
city: Detroit
country: United States
facility: Wayne State University / Harper Hospital Site Number : 7
state: Michigan
city: Rochester
country: United States
facility: Investigational Site Number 14
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic- Site Number : 14
state: Minnesota
city: Saint Louis
country: United States
facility: Investigational Site Number 10
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School Of Med Site Number : 10
state: Missouri
city: Cincinnati
country: United States
facility: Investigational Site Number 6
state: Ohio
city: Cincinnati
country: United States
facility: University Of Cincinnati Site Number : 6
state: Ohio
city: Portland
country: United States
facility: Investigational Site Number 22
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University- Site Number : 22
state: Oregon
city: Charleston
country: United States
facility: Investigational Site Number 19
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina- Site Number : 19
state: South Carolina
city: Houston
country: United States
facility: Anderson Cancer Center Site Number : 13
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 13
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care Site Number : 21
state: Vermont
city: Burlington
country: United States
facility: Investigational Site Number 21
state: Vermont
city: St Leonards
country: Australia
facility: Investigational Site Number 1001
city: Wien
country: Austria
facility: Investigational Site Number 1901
city: Wien
country: Austria
facility: Investigational Site Number : 1901
city: Anderlecht
country: Belgium
facility: Investigational Site Number : 1101
city: Bruxelles
country: Belgium
facility: Investigational Site Number 1101
city: Leuven
country: Belgium
facility: Investigational Site Number 1102
city: Leuven
country: Belgium
facility: Investigational Site Number : 1102
city: Porto Alegre
country: Brazil
facility: Hospital De Clinicas De Porto Alegre- Site Number : 2301
state: Rio Grande Do Sul
city: Ribeirao Preto
country: Brazil
facility: Faculdade de Medicina de Ribeirao Preto - USP- Site Number : 2302
state: São Paulo
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 2301
city: Ribeirão Preto
country: Brazil
facility: Investigational Site Number 2302
city: Calgary
country: Canada
facility: Investigational Site Number : 1203
state: Alberta
city: Moncton
country: Canada
facility: Investigational Site Number : 1201
state: New Brunswick
city: London
country: Canada
facility: Investigational Site Number : 1202
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1205
state: Ontario
city: Sherbrooke
country: Canada
facility: Investigational Site Number : 1204
state: Quebec
city: Calgary
country: Canada
facility: Investigational Site Number 1203
city: London
country: Canada
facility: Investigational Site Number 1202
city: Moncton
country: Canada
facility: Investigational Site Number 1201
city: Sherbrooke
country: Canada
facility: Investigational Site Number 1204
city: Toronto
country: Canada
facility: Investigational Site Number 1205
city: Praha 5
country: Czechia
facility: Investigational Site Number 3601
city: Praha 5
country: Czechia
facility: Investigational Site Number : 3601
city: Odense C
country: Denmark
facility: Investigational Site Number 2701
city: Odense C
country: Denmark
facility: Investigational Site Number : 2701
city: BORDEAUX Cedex
country: France
facility: Investigational Site Number 2802
city: BORDEAUX Cedex
country: France
facility: Investigational Site Number : 2802
city: LYON Cedex 8
country: France
facility: Investigational Site Number 2803
city: LYON Cedex 8
country: France
facility: Investigational Site Number : 2803
city: Villejuif
country: France
facility: Investigational Site Number 2801
city: Villejuif
country: France
facility: Investigational Site Number : 2801
city: Essen
country: Germany
facility: Investigational Site Number 2002
city: Essen
country: Germany
facility: Investigational Site Number : 2002
city: Halle
country: Germany
facility: Investigational Site Number 2001
city: Halle
country: Germany
facility: Investigational Site Number : 2001
city: Würzburg
country: Germany
facility: Investigational Site Number 2005
city: Würzburg
country: Germany
facility: Investigational Site Number : 2005
city: Pécs
country: Hungary
facility: Investigational Site Number 1601
city: Pécs
country: Hungary
facility: Investigational Site Number : 1601
city: Mumbai
country: India
facility: Investigational Site Number 1401
city: Mumbai
country: India
facility: Investigational Site Number : 1401
city: Vellore
country: India
facility: Investigational Site Number 1402
city: Vellore
country: India
facility: Investigational Site Number : 1402
city: Catania
country: Italy
facility: Investigational Site Number 2506
city: Catania
country: Italy
facility: Investigational Site Number : 2506
city: Milano
country: Italy
facility: Investigational Site Number 2502
city: Milano
country: Italy
facility: Investigational Site Number : 2502
city: Napoli
country: Italy
facility: Investigational Site Number 2503
city: Napoli
country: Italy
facility: Investigational Site Number : 2503
city: Pisa
country: Italy
facility: Investigational Site Number 2501
city: Pisa
country: Italy
facility: Investigational Site Number : 2501
city: Roma
country: Italy
facility: Investigational Site Number 2505
city: Roma
country: Italy
facility: Investigational Site Number : 2505
city: Siena
country: Italy
facility: Investigational Site Number 2504
city: Siena
country: Italy
facility: Investigational Site Number : 2504
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 1501
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 1501
city: Cd. Madero
country: Mexico
facility: Investigational Site Number 2403
city: Mexico City
country: Mexico
facility: Investigational Site Number 2402
city: México
country: Mexico
facility: Investigational Site Number 2404
city: México
country: Mexico
facility: Investigational Site Number : 2404
city: Groningen
country: Netherlands
facility: Investigational Site Number 2902
city: Groningen
country: Netherlands
facility: Investigational Site Number : 2902
city: Utrecht
country: Netherlands
facility: Investigational Site Number 2901
city: Utrecht
country: Netherlands
facility: Investigational Site Number : 2901
city: Warszawa
country: Poland
facility: Investigational Site Number : 1703
state: Mazowieckie
city: Poznan
country: Poland
facility: Investigational Site Number : 1702
state: Wielkopolskie
city: Gliwice
country: Poland
facility: Investigational Site Number 1701
city: Gliwice
country: Poland
facility: Investigational Site Number : 1701
city: Poznan
country: Poland
facility: Investigational Site Number 1702
city: Warszawa
country: Poland
facility: Investigational Site Number 1703
city: Coimbra
country: Portugal
facility: Investigational Site Number 2602
city: Lisboa
country: Portugal
facility: Investigational Site Number 2601
city: Lisboa
country: Portugal
facility: Investigational Site Number : 2601
city: Bucarest
country: Romania
facility: Investigational Site Number 1801
city: Obninsk
country: Russian Federation
facility: Investigational Site Number 3301
city: Obninsk
country: Russian Federation
facility: Investigational Site Number : 3301
city: Belgrade
country: Serbia
facility: Investigational Site Number 3402
city: Belgrade
country: Serbia
facility: Investigational Site Number : 3402
city: Belgrad
country: Serbia
facility: Investigational Site Number 3401
city: Belgrad
country: Serbia
facility: Investigational Site Number : 3401
city: Pamplona
country: Spain
facility: Investigational Site Number : 3002
state: Navarra
city: Madrid
country: Spain
facility: Investigational Site Number 3003
city: Madrid
country: Spain
facility: Investigational Site Number : 3003
city: Madrid
country: Spain
facility: Investigational Site Number 3001
city: Madrid
country: Spain
facility: Investigational Site Number : 3001
city: Pamplona
country: Spain
facility: Investigational Site Number 3002
city: Stockholm
country: Sweden
facility: Investigational Site Number 3102
city: Stockholm
country: Sweden
facility: Investigational Site Number : 3102
city: Uppsala
country: Sweden
facility: Investigational Site Number 3101
city: Uppsala
country: Sweden
facility: Investigational Site Number : 3101
city: Basel
country: Switzerland
facility: Investigational Site Number 2101
city: Basel
country: Switzerland
facility: Investigational Site Number : 2101
city: Bern
country: Switzerland
facility: Investigational Site Number 2102
city: Bern
country: Switzerland
facility: Investigational Site Number : 2102
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1200/JCO.2011.35.5040. Epub 2011 Oct 24.