An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer

Thyroid Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00410761
• Other study ID #: D4200C00058
• Secondary ID: 2005-005077-29LP
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 30, 2006
• Est. completion date: June 28, 2024

Study information

• Verified date: September 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 437
• Est. completion date: June 28, 2024
• Est. primary completion date: July 31, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Neuroendocrine
• Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• ZD6474 (Vandetanib)
once daily oral tablet

Locations

Country	Name	City	State
Australia	Investigational Site Number 1001	St Leonards
Austria	Investigational Site Number 1901	Wien
Belgium	Investigational Site Number 1101	Bruxelles
Belgium	Investigational Site Number 1102	Leuven
Brazil	Investigational Site Number 2301	Porto Alegre
Brazil	Investigational Site Number 2302	Ribeirão Preto
Canada	Investigational Site Number 1203	Calgary
Canada	Investigational Site Number 1202	London
Canada	Investigational Site Number 1201	Moncton
Canada	Investigational Site Number 1204	Sherbrooke
Canada	Investigational Site Number 1205	Toronto
Czechia	Investigational Site Number 3601	Praha 5
Denmark	Investigational Site Number 2701	Odense C
France	Investigational Site Number 2802	BORDEAUX Cedex
France	Investigational Site Number 2803	LYON Cedex 8
France	Investigational Site Number 2801	Villejuif
Germany	Investigational Site Number 2002	Essen
Germany	Investigational Site Number 2001	Halle
Germany	Investigational Site Number 2005	Würzburg
Hungary	Investigational Site Number 1601	Pécs
India	Investigational Site Number 1401	Mumbai
India	Investigational Site Number 1402	Vellore
Italy	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
Korea, Republic of	Investigational Site Number 1501	Seoul
Mexico	Investigational Site Number 2403	Cd. Madero
Mexico	Investigational Site Number 2404	México
Mexico	Investigational Site Number 2402	Mexico City
Netherlands	Investigational Site Number 2902	Groningen
Netherlands	Investigational Site Number 2901	Utrecht
Poland	Investigational Site Number 1701	Gliwice
Poland	Investigational Site Number 1702	Poznan
Poland	Investigational Site Number 1703	Warszawa
Portugal	Investigational Site Number 2602	Coimbra
Portugal	Investigational Site Number 2601	Lisboa
Romania	Investigational Site Number 1801	Bucarest
Russian Federation	Investigational Site Number 3301	Obninsk
Serbia	Investigational Site Number 3401	Belgrad
Serbia	Investigational Site Number 3402	Belgrade
Spain	Investigational Site Number 3001	Madrid
Spain	Investigational Site Number 3003	Madrid
Spain	Investigational Site Number 3002	Pamplona
Sweden	Investigational Site Number 3102	Stockholm
Sweden	Investigational Site Number 3101	Uppsala
Switzerland	Investigational Site Number 2101	Basel
Switzerland	Investigational Site Number 2102	Bern
United States	Investigational Site Number 9	Aurora	Colorado
United States	Investigational Site Number 2	Boston	Massachusetts
United States	Investigational Site Number 21	Burlington	Vermont
United States	Investigational Site Number 19	Charleston	South Carolina
United States	Investigational Site Number 18	Chicago	Illinois
United States	Investigational Site Number 6	Cincinnati	Ohio
United States	Investigational Site Number 7	Detroit	Michigan
United States	Investigational Site Number 13	Houston	Texas
United States	Investigational Site Number 15	Jacksonville	Florida
United States	Investigational Site Number 17	Lexington	Kentucky
United States	Investigational Site Number 3	Little Rock	Arkansas
United States	Investigational Site Number 11	New Haven	Connecticut
United States	Investigational Site Number 22	Portland	Oregon
United States	Investigational Site Number 14	Rochester	Minnesota
United States	Investigational Site Number 10	Saint Louis	Missouri
United States	Investigational Site Number 8	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Czechia,  Denmark,  France,  Germany,  Hungary,  India,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Spain,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	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.	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.
Secondary	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	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	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	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	Overall Survival (OS)	As data was immature at data cut off, number of death events is quoted	Number of deaths since randomisation
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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.

External Links

•   CSR-D4200C00058.pdf