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An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer

Primary Purpose

Thyroid Cancer

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ZD6474 (Vandetanib)
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thyroid Cancer focused on measuring ZD6474, MTC, Hereditary Medullary Thyroid Cancer, Sporadic Medullary Thyroid Cancer, Medullary Thyroid Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Investigational Site Number 3
  • Investigational Site Number 8
  • Investigational Site Number 9
  • Investigational Site Number 11
  • Investigational Site Number 15
  • Investigational Site Number 18
  • Investigational Site Number 17
  • Investigational Site Number 2
  • Investigational Site Number 7
  • Investigational Site Number 14
  • Investigational Site Number 10
  • Investigational Site Number 6
  • Investigational Site Number 22
  • Investigational Site Number 19
  • Investigational Site Number 13
  • Investigational Site Number 21
  • Investigational Site Number 1001
  • Investigational Site Number 1901
  • Investigational Site Number 1101
  • Investigational Site Number 1102
  • Investigational Site Number 2301
  • Investigational Site Number 2302
  • Investigational Site Number 1203
  • Investigational Site Number 1202
  • Investigational Site Number 1201
  • Investigational Site Number 1204
  • Investigational Site Number 1205
  • Investigational Site Number 3601
  • Investigational Site Number 2701
  • Investigational Site Number 2802
  • Investigational Site Number 2803
  • Investigational Site Number 2801
  • Investigational Site Number 2002
  • Investigational Site Number 2001
  • Investigational Site Number 2005
  • Investigational Site Number 1601
  • Investigational Site Number 1401
  • Investigational Site Number 1402
  • Investigational Site Number 2506
  • Investigational Site Number 2502
  • Investigational Site Number 2503
  • Investigational Site Number 2501
  • Investigational Site Number 2505
  • Investigational Site Number 2504
  • Investigational Site Number 1501
  • Investigational Site Number 2403
  • Investigational Site Number 2402
  • Investigational Site Number 2404
  • Investigational Site Number 2902
  • Investigational Site Number 2901
  • Investigational Site Number 1701
  • Investigational Site Number 1702
  • Investigational Site Number 1703
  • Investigational Site Number 2602
  • Investigational Site Number 2601
  • Investigational Site Number 1801
  • Investigational Site Number 3301
  • Investigational Site Number 3402
  • Investigational Site Number 3401
  • Investigational Site Number 3003
  • Investigational Site Number 3001
  • Investigational Site Number 3002
  • Investigational Site Number 3102
  • Investigational Site Number 3101
  • Investigational Site Number 2101
  • Investigational Site Number 2102

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

1

2

Arm Description

Placebo vandetanib

Vandetanib

Outcomes

Primary Outcome Measures

Progression-Free Survival(PFS)
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)
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)
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)
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)
As data was immature at data cut off, number of death events is quoted
Biochemical Response Calcitonin (CTN)
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)
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)
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.

Full Information

First Posted
December 6, 2006
Last Updated
September 22, 2023
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT00410761
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 30, 2006 (Actual)
Primary Completion Date
July 31, 2009 (Actual)
Study Completion Date
June 28, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thyroid Cancer
Keywords
ZD6474, MTC, Hereditary Medullary Thyroid Cancer, Sporadic Medullary Thyroid Cancer, Medullary Thyroid Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
437 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
No Intervention
Arm Description
Placebo vandetanib
Arm Title
2
Arm Type
Experimental
Arm Description
Vandetanib
Intervention Type
Drug
Intervention Name(s)
ZD6474 (Vandetanib)
Other Intervention Name(s)
ZACTIMA™, SAR390530
Intervention Description
once daily oral tablet
Primary Outcome Measure Information:
Title
Progression-Free Survival(PFS)
Description
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.
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.
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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.
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.
Title
Disease Control Rate (DCR)
Description
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
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
Title
Duration of Response (DoR)
Description
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
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
Title
Overall Survival (OS)
Description
As data was immature at data cut off, number of death events is quoted
Time Frame
Number of deaths since randomisation
Title
Biochemical Response Calcitonin (CTN)
Description
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.
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
Title
Biochemical Response Carcinoembryonic Antigen (CEA)
Description
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 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
Title
Time to Worsening of Pain (TWP)
Description
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.
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 3
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Investigational Site Number 8
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Investigational Site Number 9
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80010
Country
United States
Facility Name
Investigational Site Number 11
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Investigational Site Number 15
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Investigational Site Number 18
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Investigational Site Number 17
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536-0298
Country
United States
Facility Name
Investigational Site Number 2
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Investigational Site Number 7
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Investigational Site Number 14
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Investigational Site Number 10
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Investigational Site Number 6
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267-0589
Country
United States
Facility Name
Investigational Site Number 22
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Investigational Site Number 19
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Investigational Site Number 13
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Investigational Site Number 21
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Facility Name
Investigational Site Number 1001
City
St Leonards
ZIP/Postal Code
2065
Country
Australia
Facility Name
Investigational Site Number 1901
City
Wien
ZIP/Postal Code
1901
Country
Austria
Facility Name
Investigational Site Number 1101
City
Bruxelles
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Investigational Site Number 1102
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Investigational Site Number 2301
City
Porto Alegre
ZIP/Postal Code
90035-003
Country
Brazil
Facility Name
Investigational Site Number 2302
City
Ribeirão Preto
ZIP/Postal Code
14048-900
Country
Brazil
Facility Name
Investigational Site Number 1203
City
Calgary
ZIP/Postal Code
T2E7C5
Country
Canada
Facility Name
Investigational Site Number 1202
City
London
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
Investigational Site Number 1201
City
Moncton
ZIP/Postal Code
E1C6Z8
Country
Canada
Facility Name
Investigational Site Number 1204
City
Sherbrooke
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
Investigational Site Number 1205
City
Toronto
ZIP/Postal Code
M5G2M9
Country
Canada
Facility Name
Investigational Site Number 3601
City
Praha 5
ZIP/Postal Code
15006
Country
Czechia
Facility Name
Investigational Site Number 2701
City
Odense C
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Investigational Site Number 2802
City
BORDEAUX Cedex
ZIP/Postal Code
33076
Country
France
Facility Name
Investigational Site Number 2803
City
LYON Cedex 8
ZIP/Postal Code
69373
Country
France
Facility Name
Investigational Site Number 2801
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
Investigational Site Number 2002
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Investigational Site Number 2001
City
Halle
ZIP/Postal Code
06120
Country
Germany
Facility Name
Investigational Site Number 2005
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Investigational Site Number 1601
City
Pécs
ZIP/Postal Code
7624
Country
Hungary
Facility Name
Investigational Site Number 1401
City
Mumbai
ZIP/Postal Code
400012
Country
India
Facility Name
Investigational Site Number 1402
City
Vellore
ZIP/Postal Code
632004
Country
India
Facility Name
Investigational Site Number 2506
City
Catania
Country
Italy
Facility Name
Investigational Site Number 2502
City
Milano
Country
Italy
Facility Name
Investigational Site Number 2503
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Investigational Site Number 2501
City
Pisa
ZIP/Postal Code
56124
Country
Italy
Facility Name
Investigational Site Number 2505
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
Investigational Site Number 2504
City
Siena
ZIP/Postal Code
53100
Country
Italy
Facility Name
Investigational Site Number 1501
City
Seoul
Country
Korea, Republic of
Facility Name
Investigational Site Number 2403
City
Cd. Madero
Country
Mexico
Facility Name
Investigational Site Number 2402
City
Mexico City
ZIP/Postal Code
14000
Country
Mexico
Facility Name
Investigational Site Number 2404
City
México
ZIP/Postal Code
06726
Country
Mexico
Facility Name
Investigational Site Number 2902
City
Groningen
Country
Netherlands
Facility Name
Investigational Site Number 2901
City
Utrecht
Country
Netherlands
Facility Name
Investigational Site Number 1701
City
Gliwice
ZIP/Postal Code
44-101
Country
Poland
Facility Name
Investigational Site Number 1702
City
Poznan
ZIP/Postal Code
60-355
Country
Poland
Facility Name
Investigational Site Number 1703
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
Facility Name
Investigational Site Number 2602
City
Coimbra
ZIP/Postal Code
3000-75
Country
Portugal
Facility Name
Investigational Site Number 2601
City
Lisboa
ZIP/Postal Code
1099-023
Country
Portugal
Facility Name
Investigational Site Number 1801
City
Bucarest
Country
Romania
Facility Name
Investigational Site Number 3301
City
Obninsk
ZIP/Postal Code
249036
Country
Russian Federation
Facility Name
Investigational Site Number 3402
City
Belgrade
Country
Serbia
Facility Name
Investigational Site Number 3401
City
Belgrad
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Investigational Site Number 3003
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Investigational Site Number 3001
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Investigational Site Number 3002
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Investigational Site Number 3102
City
Stockholm
ZIP/Postal Code
17176
Country
Sweden
Facility Name
Investigational Site Number 3101
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
Facility Name
Investigational Site Number 2101
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Facility Name
Investigational Site Number 2102
City
Bern
ZIP/Postal Code
CH-3010
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
22025146
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. Erratum In: J Clin Oncol. 2013 Aug 20;31(24):3049.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=348&filename=CSR-D4200C00058.pdf
Description
CSR-D4200C00058.pdf

Learn more about this trial

An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer

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