Thyroid Cancer
Conditions
Keywords
Caprelsa (vandetanib), ZD6474
Brief summary
The purpose of this open label, two stage, phase II study is to evaluate the efficacy and tolerability of ZD6474 in patients with locally advanced or metastatic hereditary medullary thyroid carcinoma.
Interventions
oral once daily tablet
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Locally advanced or hereditary medullary thyroid cancer * Signed informed consent * One or more measurable lesions
Exclusion criteria
* Brain metastases or spinal cord compression * Specific laboratory ranges * Specific heart problems * Prior chemotherapy and/or radiation therapy * Participation in other trials within 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0. | 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) defined according to RECIST 1.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Objective Response | Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0. | Median duration of objective response as defined according to RECIST 1.0 from onset of response until data of objective disease progression or death from any cause in days. |
| Disease Control Rate | Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0. | Disease control rate was defined as the number of patients who had a best response of Complete Response (CR), or Partial Response (PR) or stable disease (SD) ≥24 weeks as defined according to RECIST 1.0. |
| Progression Free Survival | Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0. | Median time to progression defined according to RECIST 1.0 (months) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. |
| Symptomatic Response | Symptomatic diarrhea was assessed using stool frequency and consistency diaries. Baseline was established using the average of the 4 days immediately prior to first dose on Day 5. Diaries were completed every day for the first 6 months on study drug. | Number of participants with a reduction of frequency and improvement in consistency of stool to normal (no more than 2 solid stools daily without concomitant anti-diarrheal medication) following administration of Caprelsa (vandetanib) denoted a symptomatic CR. An improvement in stool consistency to mostly semisolid and decrease in stool frequency to 50% or greater denoted symptomatic PR. |
| World Health Organisation (WHO) Performance Status | Performance status was assessed using the WHO criteria at baseline and because SD lasting for at least 24 weeks was used in the definition of disease control (in addition to confirmed objective response), WHO PS at 24 weeks was evaluated. | Number of patients demonstrating a worsening (increase in score of one or more from baseline) in WHO PS from baseline to 24 weeks. WHO PS is scored zero (Fully active) to 4 (completely disabled) |
| Biochemical Response Calcitonin (CTN) | Blood samples for analysis of CTN taken on Day 1 (every 3 hours for 24 hours), then a single sample on Day 5, weekly through the first 2 assessment periods, monthly (prior to amendment 7) and every 12 weeks (following amendments) until discontinuation | A patient's best biochemical response was calculated from assessments performed at baseline and during treatment. Responders were those patients with a confirmed best biochemical response of Complete Response or Partial (i.e. complete normalization of CTN or at least a 50% decrease in CTN from baseline). |
Countries
France, United States
Participant flow
Recruitment details
First patient enrolled 12 November 2004, last patient enrolled 15 August 2006, cut off date 22 February 2008. 40 patients were enrolled in the study.
Pre-assignment details
40 patients were enrolled/screened to the study but only 30 patients were entered treatment/randomized.
Participants by arm
| Arm | Count |
|---|---|
| Caprelsa (Vandetanib) 300 mg Daily oral dose of Caprelsa (vandetanib) 300mg | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | progression | 4 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Caprelsa (Vandetanib) 300 mg |
|---|---|
| Age, Continuous | 48.7 years |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 30 |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 14 / 30 |
Outcome results
Primary
Objective Response Rate
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) defined according to RECIST 1.0.
Time frame: Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caprelsa (Vandetanib) 300 mg | Objective Response Rate | 6 Participants |
Secondary
Biochemical Response Calcitonin (CTN)
A patient's best biochemical response was calculated from assessments performed at baseline and during treatment. Responders were those patients with a confirmed best biochemical response of Complete Response or Partial (i.e. complete normalization of CTN or at least a 50% decrease in CTN from baseline).
Time frame: Blood samples for analysis of CTN taken on Day 1 (every 3 hours for 24 hours), then a single sample on Day 5, weekly through the first 2 assessment periods, monthly (prior to amendment 7) and every 12 weeks (following amendments) until discontinuation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caprelsa (Vandetanib) 300 mg | Biochemical Response Calcitonin (CTN) | 24 Participants |
Secondary
Disease Control Rate
Disease control rate was defined as the number of patients who had a best response of Complete Response (CR), or Partial Response (PR) or stable disease (SD) ≥24 weeks as defined according to RECIST 1.0.
Time frame: Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caprelsa (Vandetanib) 300 mg | Disease Control Rate | 22 Participants |
Secondary
Duration of Objective Response
Median duration of objective response as defined according to RECIST 1.0 from onset of response until data of objective disease progression or death from any cause in days.
Time frame: Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Caprelsa (Vandetanib) 300 mg | Duration of Objective Response | 310.5 days |
Secondary
Progression Free Survival
Median time to progression defined according to RECIST 1.0 (months) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment.
Time frame: Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0.
Population: Upper limit is a censored value
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Caprelsa (Vandetanib) 300 mg | Progression Free Survival | 27.9 months |
Secondary
Symptomatic Response
Number of participants with a reduction of frequency and improvement in consistency of stool to normal (no more than 2 solid stools daily without concomitant anti-diarrheal medication) following administration of Caprelsa (vandetanib) denoted a symptomatic CR. An improvement in stool consistency to mostly semisolid and decrease in stool frequency to 50% or greater denoted symptomatic PR.
Time frame: Symptomatic diarrhea was assessed using stool frequency and consistency diaries. Baseline was established using the average of the 4 days immediately prior to first dose on Day 5. Diaries were completed every day for the first 6 months on study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caprelsa (Vandetanib) 300 mg | Symptomatic Response | 0 Participants |
Secondary
World Health Organisation (WHO) Performance Status
Number of patients demonstrating a worsening (increase in score of one or more from baseline) in WHO PS from baseline to 24 weeks. WHO PS is scored zero (Fully active) to 4 (completely disabled)
Time frame: Performance status was assessed using the WHO criteria at baseline and because SD lasting for at least 24 weeks was used in the definition of disease control (in addition to confirmed objective response), WHO PS at 24 weeks was evaluated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caprelsa (Vandetanib) 300 mg | World Health Organisation (WHO) Performance Status | 4 Participants |