A Study To Assess ZD6474 (ZACTIMA™) Monotherapy In Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer

Phase 2

Completed

• Conditions: Thyroid Cancer
• Interventions: Drug: ZD6474 (vandetanib)

• Registration Number: NCT00358956
• Lead Sponsor: Genzyme, a Sanofi Company

Brief Summary

This will be a Phase II, open label study to establish the effect of once-daily oral doses of ZD6474 100mg in subjects with locally advanced or metastatic hereditary medullary thyroid cancer in whom no standard therapeutic option is available.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2006-07-28
• Study First Submitted QC: 2006-07-28
• Study Start: 2006-08
• Study First Posted: 2006-08-01
• Primary Completion: 2008-01
• Disposition First Submitted: 2011-03-28
• Disposition First Submitted QC: 2011-03-28
• Disposition First Posted: 2011-04-06
• Results First Submitted: 2011-04-27
• Results First Submitted QC: 2012-07-30
• Results First Posted: 2012-08-31
• Study Completion: 2014-05
• Status Verified: 2016-12
• Last Update Submitted: 2016-12-07
• Last Update Posted: 2017-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

• Provision of written informed consent
• Previously confirmed histological diagnosis of locally advanced or metastatic hereditary medullary thyroid carcinoma without standard therapeutic options
• Aged 18 or over and a life expectancy of more than 12 weeks

Exclusion Criteria

• The last dose of prior chemo/radiation received less than 4 weeks before the start of study therapy
• Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age, history of arrhythmia

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	ZD6474 (vandetanib)	-

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment.	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.

Secondary Outcome Measures

Name	Time	Method
World Heath Organization (WHO) Performance Status	WHO PS assessed at screening (up to 3 weeks prior to first dose), baseline and then every 12 weeks (± 2 weeks), up to and including discontinuation of study treatment.	Number of patients demonstrating an improvement from baseline to 24 weeks in WHO PS. Where WHO PS is the standard scale with patients scored (0 healthy - 5 dead) based on their physical capabilities
Symptomatic Response	Symptomatic diarrhea was assessed using stool frequency diaries. Baseline was established using the average of the 4 days immediately prior to first dose, then weekly until discontinuation of study treatment.	Symptomatic response will be defined as at least a 50% decrease in the stool frequency (represented by a persistent decrease in stool frequency over 4 weeks), taking as reference the baseline (mean) level.
Biochemical Response Carcinoembryonic Antigen CEA)	Blood samples for analysis of CTN were taken at screening (0, 1, 4, and 8 hours to determine the baseline CTN/CEA level) then every 4 weeks until discontinuation	A patient's best biochemical response was calculated from assessments performed 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 Partial Response (PR) or Complete Response (CR) were first met.
Progression-Free Survival (PFS)	RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment.	Median progression free survival (months) estimated from a Weibull model with corresponding 95% confidence intervals. Progression free survival is the time 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.
Disease Control Rate (DCR)	RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment.	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) \>= 24 weeks
Biochemical Response Calcitonin (CTN )	Blood samples for analysis of CTN were taken at screening (0, 1, 4, and 8 hours to determine the baseline CTN/CEA level) then every 4 weeks until discontinuation Time point(s) at which outcome measure was assessed. (Limit: 255 characters)	A patient's best biochemical response was calculated from assessments performed 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.

Trial Locations

Locations (1)

Research Site; 🇨🇭 Basel, Switzerland