An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer

September 4, 2025 updated by: Genzyme, a Sanofi Company

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

331

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • St Leonards, Australia, 2065
        • Investigational Site Number 1001
  • Austria
      • Vienna, Austria, 1901
        • Investigational Site Number 1901
      • Vienna, Austria, 1901
        • Investigational Site Number : 1901
  • Belgium
      • Anderlecht, Belgium, 1070
        • Investigational Site Number : 1101
      • Brussels, Belgium, 1000
        • Investigational Site Number 1101
      • Leuven, Belgium, 3000
        • Investigational Site Number 1102
      • Leuven, Belgium, 3000
        • Investigational Site Number : 1102
  • Brazil
      • Porto Alegre, Brazil, 90035-003
        • Investigational Site Number 2301
      • Ribeirão Preto, Brazil, 14048-900
        • Investigational Site Number 2302
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90035-003
        • Hospital De Clinicas De Porto Alegre- Site Number : 2301
    • São Paulo
      • Ribeirão Preto, São Paulo, Brazil, 14048-900
        • Faculdade de Medicina de Ribeirao Preto - USP- Site Number : 2302
  • Canada
      • Calgary, Canada, T2E7C5
        • Investigational Site Number 1203
      • London, Canada, N6A 4L6
        • Investigational Site Number 1202
      • Moncton, Canada, E1C6Z8
        • Investigational Site Number 1201
      • Sherbrooke, Canada, J1H 5N4
        • Investigational Site Number 1204
      • Toronto, Canada, M5G2M9
        • Investigational Site Number 1205
    • Alberta
      • Calgary, Alberta, Canada, T2E7C5
        • Investigational Site Number : 1203
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C6Z8
        • Investigational Site Number : 1201
    • Ontario
      • London, Ontario, Canada, N6A 4L6
        • Investigational Site Number : 1202
      • Toronto, Ontario, Canada, M5G2M9
        • Investigational Site Number : 1205
    • Quebec
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Investigational Site Number : 1204
  • Czechia
      • Prague, Czechia, 15006
        • Investigational Site Number 3601
      • Prague, Czechia, 15006
        • Investigational Site Number : 3601
  • Denmark
      • Odense C, Denmark, 5000
        • Investigational Site Number 2701
      • Odense C, Denmark, 5000
        • Investigational Site Number : 2701
  • France
      • Bordeaux, France, 33076
        • Investigational Site Number 2802
      • Bordeaux, France, 33076
        • Investigational Site Number : 2802
      • Lyon, France, 69373
        • Investigational Site Number 2803
      • Lyon, France, 69373
        • Investigational Site Number : 2803
      • Villejuif, France, 94800
        • Investigational Site Number 2801
      • Villejuif, France, 94800
        • Investigational Site Number : 2801
  • Germany
      • Essen, Germany, 45122
        • Investigational Site Number 2002
      • Essen, Germany, 45122
        • Investigational Site Number : 2002
      • Halle, Germany, 06120
        • Investigational Site Number 2001
      • Halle, Germany, 06120
        • Investigational Site Number : 2001
      • Würzburg, Germany, 97080
        • Investigational Site Number 2005
      • Würzburg, Germany, 97080
        • Investigational Site Number : 2005
  • Hungary
      • Pécs, Hungary, 7624
        • Investigational Site Number 1601
      • Pécs, Hungary, 7624
        • Investigational Site Number : 1601
  • India
      • Mumbai, India, 400012
        • Investigational Site Number 1401
      • Mumbai, India, 400012
        • Investigational Site Number : 1401
      • Vellore, India, 632004
        • Investigational Site Number 1402
      • Vellore, India, 632004
        • Investigational Site Number : 1402
  • Italy
      • Catania, Italy
        • Investigational Site Number 2506
      • Catania, Italy
        • Investigational Site Number : 2506
      • Milan, Italy
        • Investigational Site Number 2502
      • Milan, Italy
        • Investigational Site Number : 2502
      • Napoli, Italy, 80131
        • Investigational Site Number 2503
      • Napoli, Italy, 80131
        • Investigational Site Number : 2503
      • Pisa, Italy, 56124
        • Investigational Site Number 2501
      • Pisa, Italy, 56124
        • Investigational Site Number : 2501
      • Roma, Italy, 00161
        • Investigational Site Number 2505
      • Roma, Italy, 00161
        • Investigational Site Number : 2505
      • Siena, Italy, 53100
        • Investigational Site Number 2504
      • Siena, Italy, 53100
        • Investigational Site Number : 2504
  • Mexico
      • Ciudad Madero, Mexico
        • Investigational Site Number 2403
      • Mexico City, Mexico, 14000
        • Investigational Site Number 2402
      • México, Mexico, 06726
        • Investigational Site Number 2404
      • México, Mexico, 06726
        • Investigational Site Number : 2404
  • Netherlands
      • Groningen, Netherlands
        • Investigational Site Number 2902
      • Groningen, Netherlands
        • Investigational Site Number : 2902
      • Utrecht, Netherlands
        • Investigational Site Number 2901
      • Utrecht, Netherlands
        • Investigational Site Number : 2901
  • Poland
      • Gliwice, Poland, 44-101
        • Investigational Site Number 1701
      • Gliwice, Poland, 44-101
        • Investigational Site Number : 1701
      • Poznan, Poland, 60-355
        • Investigational Site Number 1702
      • Warsaw, Poland, 02-781
        • Investigational Site Number 1703
    • Greater Poland Voivodeship
      • Poznan, Greater Poland Voivodeship, Poland, 60-355
        • Investigational Site Number : 1702
    • Masovian Voivodeship
      • Warsaw, Masovian Voivodeship, Poland, 02-781
        • Investigational Site Number : 1703
  • Portugal
      • Coimbra, Portugal, 3000-75
        • Investigational Site Number 2602
      • Lisbon, Portugal, 1099-023
        • Investigational Site Number 2601
      • Lisbon, Portugal, 1099-023
        • Investigational Site Number : 2601
  • Romania
      • Bucharest, Romania
        • Investigational Site Number 1801
  • Russia
      • Obninsk, Russia, 249036
        • Investigational Site Number 3301
      • Obninsk, Russia, 249036
        • Investigational Site Number : 3301
  • Serbia
      • Belgrade, Serbia
        • Investigational Site Number 3402
      • Belgrade, Serbia
        • Investigational Site Number : 3402
      • Belgrade, Serbia, 11000
        • Investigational Site Number 3401
      • Belgrade, Serbia, 11000
        • Investigational Site Number : 3401
  • South Korea
      • Seoul, South Korea, 03080
        • Investigational Site Number : 1501
      • Seoul, South Korea
        • Investigational Site Number 1501
  • Spain
      • Madrid, Spain, 28040
        • Investigational Site Number 3003
      • Madrid, Spain, 28041
        • Investigational Site Number 3001
      • Madrid, Spain, 28040
        • Investigational Site Number : 3003
      • Madrid, Spain, 28041
        • Investigational Site Number : 3001
      • Pamplona, Spain, 31008
        • Investigational Site Number 3002
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Investigational Site Number : 3002
  • Sweden
      • Stockholm, Sweden, 17176
        • Investigational Site Number 3102
      • Stockholm, Sweden, 17176
        • Investigational Site Number : 3102
      • Uppsala, Sweden, 75185
        • Investigational Site Number 3101
      • Uppsala, Sweden, 75185
        • Investigational Site Number : 3101
  • Switzerland
      • Basel, Switzerland, 4031
        • Investigational Site Number 2101
      • Basel, Switzerland, 4031
        • Investigational Site Number : 2101
      • Bern, Switzerland, CH-3010
        • Investigational Site Number 2102
      • Bern, Switzerland, CH-3010
        • Investigational Site Number : 2102
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Investigational Site Number 3
      • Little Rock, Arkansas, United States, 72205
        • University Arkansas Site Number : 3
    • California
      • San Francisco, California, United States, 94115
        • Investigational Site Number 8
      • San Francisco, California, United States, 94115
        • USCF / Mt Zion Medical Center Site Number : 8
    • Colorado
      • Aurora, Colorado, United States, 80010
        • Investigational Site Number 9
      • Aurora, Colorado, United States, 80010
        • University Of Colorado Health Sciences Center Site Number : 9
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Investigational Site Number 11
      • New Haven, Connecticut, United States, 06510
        • Yale University School Medicine Site Number : 11
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Investigational Site Number 15
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic- Site Number : 15
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Investigational Site Number 18
      • Chicago, Illinois, United States, 60637
        • The University Of Chicago Site Number : 18
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0298
        • Investigational Site Number 17
      • Lexington, Kentucky, United States, 40536-0298
        • The University Of Kentucky Site Number : 17
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Investigational Site Number 2
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute Site Number : 2
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Investigational Site Number 7
      • Detroit, Michigan, United States, 48201
        • Wayne State University / Harper Hospital Site Number : 7
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Investigational Site Number 14
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic- Site Number : 14
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Investigational Site Number 10
      • St Louis, Missouri, United States, 63110
        • Washington University School Of Med Site Number : 10
    • Ohio
      • Cincinnati, Ohio, United States, 45267-0589
        • Investigational Site Number 6
      • Cincinnati, Ohio, United States, 45267-0589
        • University Of Cincinnati Site Number : 6
    • Oregon
      • Portland, Oregon, United States, 97239
        • Investigational Site Number 22
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University- Site Number : 22
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Investigational Site Number 19
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina- Site Number : 19
    • Texas
      • Houston, Texas, United States, 77030
        • Investigational Site Number 13
      • Houston, Texas, United States, 77030
        • Anderson Cancer Center Site Number : 13
    • Vermont
      • Burlington, Vermont, United States, 05401
        • Investigational Site Number 21
      • Burlington, Vermont, United States, 05401
        • Fletcher Allen Health Care Site Number : 21

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 2
Vandetanib
Drug: ZD6474 (Vandetanib)
once daily oral tablet
Other Names:
  • ZACTIMA™
  • SAR390530
No Intervention: 1
Placebo vandetanib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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.
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 Measures

Outcome Measure
Measure Description
Time Frame
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.

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 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.
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
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
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
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
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
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
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
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.
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
Overall Survival (OS)
Time Frame: From date of randomization until death, up to approximately 105 months
OS is defined as the time from the date of randomization until death.
From date of randomization until death, up to approximately 105 months
Biochemical Response Calcitonin (CTN)
Time Frame: 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
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.
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
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.
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. TWP results are presented.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genzyme, a Sanofi Company

Investigators

  • Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 23, 2006

Primary Completion (Actual)

July 31, 2009

Study Completion (Actual)

July 26, 2024

Study Registration Dates

First Submitted

December 6, 2006

First Submitted That Met QC Criteria

December 12, 2006

First Posted (Estimated)

December 13, 2006

Study Record Updates

Last Update Posted (Estimated)

September 24, 2025

Last Update Submitted That Met QC Criteria

September 4, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D4200C00058
  • 2005-005077-29 (EudraCT Number)
  • LPS14811 (Other Identifier: Sanofi Identifier)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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