Non-Small-Cell Lung Carcinoma
Conditions
Keywords
Non-Small-Cell Lung Carcinoma, Adenocarcinoma, Squamous Cell Carcinoma, Large Cell Carcinoma
Brief summary
This study is being carried out to assess if adding ZD6474 to best supportive care (BSC) is more effective than best supportive care alone, for the treatment of patients with non-small cell lung cancer, whose disease has recurred after previous chemotherapy and an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI). ZD6474 is a new anti-cancer drug in development that works in a different way to standard chemotherapy drugs. It targets the growth of new blood vessels to a tumour and thereby might slow the rate at which the tumour may grow. Early studies indicate that ZD6474 has a positive effect on the time that a tumour may take to progress to a further stage. Approximately 930 patients will take part in this study. It will be conducted in hospitals and clinics in North and South America, Europe and Asia.
Interventions
once daily oral tablet
OTHERBest Supportive Care
standard of care
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with Non-small cell lung cancer for which the standard cancer treatments of surgery, chemotherapy, radiation or other anticancer drugs are no longer appropriate treatments for you.
Exclusion criteria
* Patients who have had standard cancer treatments of surgery, chemotherapy or other systemic anti-cancer therapy within 4 weeks before start of study therapy. * Three or more prior chemotherapy regimens. * Significant cardiovascular events.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Time to death in months | Overall Survival (OS) is defined as the time from date of randomization until death. Any blinded/unknown patient which have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie, their status must be known at the censored date and should not be lost to follow up or unknown). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression | Median time (in 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 |
| Objective Response Rate (ORR) | Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression. | 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)\>= 8 weeks, progressive disease (PD) or NE. |
| Disease Control Rate (DCR) | RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression | 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) \>= 8 weeks |
| Duration of Response (DoR) | RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression | 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) |
| Time to Deterioration of Disease-related Symptoms (TDS) by Questionnaire - the Lung Cancer Subscale (LCS) a Selection of the FACT-L Focusing on Symptoms of Lung Cancer Plus Pain and Fatigue (LCS-PF) | Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication) and every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit | Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days. Where assessment is by a selection of questions from the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire. |
Countries
Argentina, Australia, Austria, Belgium, Canada, China, France, Germany, Hong Kong, Israel, Italy, Mexico, Netherlands, Peru, Philippines, Singapore, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States
Participant flow
Recruitment details
First patient enrolled 08 November 2006, last patient enrolled 09 October 2008, cut off date 19 October 2009. 1168 patients were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Vandetanib 300 mg vandetanib (300 mg daily) plus best supportive care | 617 |
| Placebo Placebo plus best supportive care | 307 |
| Total | 924 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 75 | 16 |
| Overall Study | Condition under investigation worsened | 475 | 264 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other | 25 | 11 |
| Overall Study | Randomised but not received treatment | 1 | 1 |
| Overall Study | Withdrawal by Subject | 26 | 13 |
Baseline characteristics
| Characteristic | Vandetanib 300 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 59.8 years | 60.6 years | 60 years |
| Sex: Female, Male Female | 329 Participants | 160 Participants | 489 Participants |
| Sex: Female, Male Male | 288 Participants | 147 Participants | 435 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 557 / 619 | 234 / 303 |
| serious Total, serious adverse events | 160 / 619 | 63 / 303 |
Outcome results
Primary
Overall Survival (OS)
Overall Survival (OS) is defined as the time from date of randomization until death. Any blinded/unknown patient which have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie, their status must be known at the censored date and should not be lost to follow up or unknown).
Time frame: Time to death in months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vandetanib 300 mg | Overall Survival (OS) | 8.5 Months |
| Placebo | Overall Survival (OS) | 7.8 Months |
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) \>= 8 weeks
Time frame: RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vandetanib 300 mg | Disease Control Rate (DCR) | 189 Participants |
| Placebo | Disease Control Rate (DCR) | 48 Participants |
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)
Time frame: RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vandetanib 300 mg | Duration of Response (DoR) | 23.9 Weeks |
| Placebo | Duration of Response (DoR) | 24.3 Weeks |
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)\>= 8 weeks, progressive disease (PD) or NE.
Time frame: Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vandetanib 300 mg | Objective Response Rate (ORR) | 16 Participants |
| Placebo | Objective Response Rate (ORR) | 2 Participants |
Secondary
Progression-Free Survival (PFS)
Median time (in 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
Time frame: RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vandetanib 300 mg | Progression-Free Survival (PFS) | 1.9 month |
| Placebo | Progression-Free Survival (PFS) | 1.8 month |
Secondary
Time to Deterioration of Disease-related Symptoms (TDS) by Questionnaire - the Lung Cancer Subscale (LCS) a Selection of the FACT-L Focusing on Symptoms of Lung Cancer Plus Pain and Fatigue (LCS-PF)
Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days. Where assessment is by a selection of questions from the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire.
Time frame: Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication) and every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vandetanib 300 mg | Time to Deterioration of Disease-related Symptoms (TDS) by Questionnaire - the Lung Cancer Subscale (LCS) a Selection of the FACT-L Focusing on Symptoms of Lung Cancer Plus Pain and Fatigue (LCS-PF) | 6.1 weeks |
| Placebo | Time to Deterioration of Disease-related Symptoms (TDS) by Questionnaire - the Lung Cancer Subscale (LCS) a Selection of the FACT-L Focusing on Symptoms of Lung Cancer Plus Pain and Fatigue (LCS-PF) | 7.1 weeks |