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An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer

Phase 3
Completed
Conditions
Thyroid Cancer
Interventions
Drug: ZD6474 (Vandetanib)
Registration Number
NCT00410761
Lead Sponsor
Genzyme, a Sanofi Company
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
437
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
2ZD6474 (Vandetanib)Vandetanib
Primary Outcome Measures
NameTimeMethod
Progression-Free Survival(PFS)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then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent.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.

Secondary Outcome Measures
NameTimeMethod
Biochemical Response Calcitonin (CTN)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

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.

Objective Response Rate (ORR)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.

Biochemical Response Carcinoembryonic Antigen (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

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.

Disease Control Rate (DCR)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

Duration of Response (DoR)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

Overall Survival (OS)Number of deaths since randomisation

As data was immature at data cut off, number of death events is quoted

Time to Worsening of Pain (TWP)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.

Trial Locations

Locations (127)

University Arkansas Site Number : 3

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Little Rock, Arkansas, United States

USCF / Mt Zion Medical Center Site Number : 8

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San Francisco, California, United States

University Of Colorado Health Sciences Center Site Number : 9

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Aurora, Colorado, United States

Yale University School Medicine Site Number : 11

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New Haven, Connecticut, United States

Mayo Clinic- Site Number : 15

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Jacksonville, Florida, United States

The University Of Chicago Site Number : 18

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Chicago, Illinois, United States

The University Of Kentucky Site Number : 17

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Lexington, Kentucky, United States

Dana Farber Cancer Institute Site Number : 2

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Boston, Massachusetts, United States

Wayne State University / Harper Hospital Site Number : 7

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Detroit, Michigan, United States

Mayo Clinic- Site Number : 14

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Rochester, Minnesota, United States

Washington University School Of Med Site Number : 10

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Saint Louis, Missouri, United States

University Of Cincinnati Site Number : 6

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Cincinnati, Ohio, United States

Oregon Health & Science University- Site Number : 22

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Portland, Oregon, United States

Medical University of South Carolina- Site Number : 19

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Charleston, South Carolina, United States

Anderson Cancer Center Site Number : 13

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Houston, Texas, United States

Fletcher Allen Health Care Site Number : 21

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Burlington, Vermont, United States

Investigational Site Number : 1901

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Wien, Austria

Investigational Site Number : 1101

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Anderlecht, Belgium

Investigational Site Number : 1102

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Leuven, Belgium

Hospital De Clinicas De Porto Alegre- Site Number : 2301

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Porto Alegre, Rio Grande Do Sul, Brazil

Faculdade de Medicina de Ribeirao Preto - USP- Site Number : 2302

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Ribeirao Preto, São Paulo, Brazil

Investigational Site Number : 1203

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Calgary, Alberta, Canada

Investigational Site Number : 1201

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Moncton, New Brunswick, Canada

Investigational Site Number : 1202

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London, Ontario, Canada

Investigational Site Number : 1205

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Toronto, Ontario, Canada

Investigational Site Number : 1204

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Sherbrooke, Quebec, Canada

Investigational Site Number : 3601

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Praha 5, Czechia

Investigational Site Number : 2701

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Odense C, Denmark

Investigational Site Number : 2802

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BORDEAUX Cedex, France

Investigational Site Number : 2803

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LYON Cedex 8, France

Investigational Site Number : 2801

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Villejuif, France

Investigational Site Number : 2002

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Essen, Germany

Investigational Site Number : 2001

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Halle, Germany

Investigational Site Number : 2005

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Würzburg, Germany

Investigational Site Number : 1601

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Pécs, Hungary

Investigational Site Number : 1401

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Mumbai, India

Investigational Site Number : 1402

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Vellore, India

Investigational Site Number : 2506

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Catania, Italy

Investigational Site Number : 2502

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Milano, Italy

Investigational Site Number : 2503

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Napoli, Italy

Investigational Site Number : 2501

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Pisa, Italy

Investigational Site Number : 2505

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Roma, Italy

Investigational Site Number : 2504

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Siena, Italy

Investigational Site Number : 1501

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Seoul, Korea, Republic of

Investigational Site Number : 2404

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México, Mexico

Investigational Site Number : 2902

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Groningen, Netherlands

Investigational Site Number : 2901

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Utrecht, Netherlands

Investigational Site Number : 1703

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Warszawa, Mazowieckie, Poland

Investigational Site Number : 1702

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Poznan, Wielkopolskie, Poland

Investigational Site Number : 1701

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Gliwice, Poland

Investigational Site Number : 2601

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Lisboa, Portugal

Investigational Site Number : 3301

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Obninsk, Russian Federation

Investigational Site Number : 3402

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Belgrade, Serbia

Investigational Site Number : 3401

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Belgrad, Serbia

Investigational Site Number : 3002

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Pamplona, Navarra, Spain

Investigational Site Number : 3003

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Madrid, Spain

Investigational Site Number : 3001

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Madrid, Spain

Investigational Site Number : 3102

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Stockholm, Sweden

Investigational Site Number : 3101

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Uppsala, Sweden

Investigational Site Number : 2101

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Basel, Switzerland

Investigational Site Number : 2102

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Bern, Switzerland

Investigational Site Number 3

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Little Rock, Arkansas, United States

Investigational Site Number 8

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San Francisco, California, United States

Investigational Site Number 9

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Aurora, Colorado, United States

Investigational Site Number 11

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New Haven, Connecticut, United States

Investigational Site Number 15

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Jacksonville, Florida, United States

Investigational Site Number 18

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Chicago, Illinois, United States

Investigational Site Number 17

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Lexington, Kentucky, United States

Investigational Site Number 2

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Boston, Massachusetts, United States

Investigational Site Number 7

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Detroit, Michigan, United States

Investigational Site Number 14

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Rochester, Minnesota, United States

Investigational Site Number 10

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Saint Louis, Missouri, United States

Investigational Site Number 6

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Cincinnati, Ohio, United States

Investigational Site Number 22

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Portland, Oregon, United States

Investigational Site Number 19

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Charleston, South Carolina, United States

Investigational Site Number 13

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Houston, Texas, United States

Investigational Site Number 21

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Burlington, Vermont, United States

Investigational Site Number 1001

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St Leonards, Australia

Investigational Site Number 1901

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Wien, Austria

Investigational Site Number 1101

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Bruxelles, Belgium

Investigational Site Number 1102

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Leuven, Belgium

Investigational Site Number 2301

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Porto Alegre, Brazil

Investigational Site Number 2302

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Ribeirão Preto, Brazil

Investigational Site Number 1203

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Calgary, Canada

Investigational Site Number 1202

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London, Canada

Investigational Site Number 1201

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Moncton, Canada

Investigational Site Number 1204

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Sherbrooke, Canada

Investigational Site Number 1205

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Toronto, Canada

Investigational Site Number 3601

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Praha 5, Czechia

Investigational Site Number 2701

🇩🇰

Odense C, Denmark

Investigational Site Number 2802

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BORDEAUX Cedex, France

Investigational Site Number 2803

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LYON Cedex 8, France

Investigational Site Number 2801

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Villejuif, France

Investigational Site Number 2002

🇩🇪

Essen, Germany

Investigational Site Number 2001

🇩🇪

Halle, Germany

Investigational Site Number 2005

🇩🇪

Würzburg, Germany

Investigational Site Number 1601

🇭🇺

Pécs, Hungary

Investigational Site Number 1401

🇮🇳

Mumbai, India

Investigational Site Number 1402

🇮🇳

Vellore, India

Investigational Site Number 2506

🇮🇹

Catania, Italy

Investigational Site Number 2502

🇮🇹

Milano, Italy

Investigational Site Number 2503

🇮🇹

Napoli, Italy

Investigational Site Number 2501

🇮🇹

Pisa, Italy

Investigational Site Number 2505

🇮🇹

Roma, Italy

Investigational Site Number 2504

🇮🇹

Siena, Italy

Investigational Site Number 1501

🇰🇷

Seoul, Korea, Republic of

Investigational Site Number 2403

🇲🇽

Cd. Madero, Mexico

Investigational Site Number 2402

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Mexico City, Mexico

Investigational Site Number 2404

🇲🇽

México, Mexico

Investigational Site Number 2902

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Groningen, Netherlands

Investigational Site Number 2901

🇳🇱

Utrecht, Netherlands

Investigational Site Number 1701

🇵🇱

Gliwice, Poland

Investigational Site Number 1702

🇵🇱

Poznan, Poland

Investigational Site Number 1703

🇵🇱

Warszawa, Poland

Investigational Site Number 2602

🇵🇹

Coimbra, Portugal

Investigational Site Number 2601

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Lisboa, Portugal

Investigational Site Number 1801

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Bucarest, Romania

Investigational Site Number 3301

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Obninsk, Russian Federation

Investigational Site Number 3402

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Belgrade, Serbia

Investigational Site Number 3401

🇷🇸

Belgrad, Serbia

Investigational Site Number 3003

🇪🇸

Madrid, Spain

Investigational Site Number 3001

🇪🇸

Madrid, Spain

Investigational Site Number 3002

🇪🇸

Pamplona, Spain

Investigational Site Number 3102

🇸🇪

Stockholm, Sweden

Investigational Site Number 3101

🇸🇪

Uppsala, Sweden

Investigational Site Number 2101

🇨🇭

Basel, Switzerland

Investigational Site Number 2102

🇨🇭

Bern, Switzerland

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