NSCLC
Conditions
Keywords
Vandetanib, NSCLC, Maintenance, Phase II
Brief summary
This study is multicenter, randomized, double-blinded, placebo-controlled Phase II study comparing vandetanib (300mg daily) plus best supportive care (BSC) to placebo plus BSC as maintenance treatment in patients with locally advanced or metastatic NSCLC, who have received and responded to prior platinum-doublet systemic chemotherapy. The primary objective of the study is to compare the Progression Free Survival (PFS) rate at 3 months in locally advanced or metastatic NSCLC patients with or without vandetanib maintenance.
Interventions
DRUGVandetanib
Tablet, oral, daily
DRUGPlacebo
Placebo
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic or cytologic confirmation of locally advanced or metastatic NSCLC (IIIb-IV) at the time of original diagnosis. * Completion of 4 cycles of chemotherapy of gemcitabine (1,000 or 1250mg/m\^2/day on day 1 and 8) and cisplatin (70-80mg/m\^2/day on day 1) every 3 weeks and have shown response, Complete Response(CR), Partial Response (PR) or stable disease (SD) by RECIST. * WHO PS 0-1 * No prior radiotherapy to chest, immunotherapy or biologic therapy
Exclusion criteria
* Mixed small cell and non small-cell lung cancer history. * Prior treatment with EGFR TKIs or VEGFR TKIs (prior treatment with cetuximab \[Erbitux\] or bevacizumab \[Avastin\] is not permitted.) * Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol. * Radiation therapy within 4 weeks before the start of study therapy. Major surgery within 4 weeks, or incomplete healed surgical incision before starting study therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Rate at 3 Months | 12 weeks | Progression-free survival (PFS) rate at 3 months is defined as the number of patients without evidence of progression or death after 3 months from randomisation among the PFS-evaluable patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression. | Progression-free survival (PFS) defined as the median time from randomization to death from any cause or first observed disease progression. |
| Overall Survival (OS) | Every 12 weeks unless the patient withdraws consent | Overall survival (OS) defined as the median time from randomization to death from any cause. |
| Disease of Response (DOR) | Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression. | Number of patients showing Complete Response (CR), Partial Response (PR) or Stable Disease (SD) based on RECIST for the best response. Number of patients showing Complete Response (CR, disappearance of all target lesions), Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) or Stable Disease (SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum longest diameter since the treatment started) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response |
| Objective Response Rate (ORR) | Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression. | Number of patients showing Complete Response (CR) or Partial Response (PR) based on RECIST for the best response. Number of patients showing Complete Response (CR, disappearance of all target lesions) or Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response. |
Countries
South Korea
Participant flow
Recruitment details
First patient enrolled: 13 October 2008 Last patient enrolled: 7 December 2009 This study was conducted at Division of oncology, Department of Medicine of general hospitals in Korea.
Participants by arm
| Arm | Count |
|---|---|
| Vandetanib Vandetanib 300 mg, orally, once daily | 75 |
| Placebo Matching Placebo | 42 |
| Total | 117 |
Baseline characteristics
| Characteristic | Placebo | Total | Vandetanib |
|---|---|---|---|
| Age, Customized Median (min-Max Range) | 60.5 year | 61 year | 61 year |
| Classification of lung tumor stage Stage IIIb | 12 Participants | 27 Participants | 15 Participants |
| Classification of lung tumor stage Stage IV | 30 Participants | 90 Participants | 60 Participants |
| Histology Adenocarcinoma | 31 Participants | 87 Participants | 56 Participants |
| Histology Other | 2 Participants | 10 Participants | 8 Participants |
| Histology Squamous cell carcinoma | 9 Participants | 20 Participants | 11 Participants |
| Overall response at screening Partial Response (PR) | 30 Participants | 74 Participants | 44 Participants |
| Overall response at screening Stable Disease (SD) | 12 Participants | 43 Participants | 31 Participants |
| Sex: Female, Male Female | 14 Participants | 42 Participants | 28 Participants |
| Sex: Female, Male Male | 28 Participants | 75 Participants | 47 Participants |
| Smoking history Non-smoker | 14 Participants | 42 Participants | 28 Participants |
| Smoking history Smoker | 28 Participants | 75 Participants | 47 Participants |
| WHO Performance status 0 | 10 Participants | 30 Participants | 20 Participants |
| WHO Performance status 1 | 32 Participants | 87 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 72 / 75 | 37 / 42 |
| serious Total, serious adverse events | 18 / 75 | 4 / 42 |
Outcome results
Primary
Progression-free Survival (PFS) Rate at 3 Months
Progression-free survival (PFS) rate at 3 months is defined as the number of patients without evidence of progression or death after 3 months from randomisation among the PFS-evaluable patients.
Time frame: 12 weeks
Population: The reported number of participants analyzed (Vandetanib: 63, Placebo: 38) are for PFS evaluable patient set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vandetanib | Progression-free Survival (PFS) Rate at 3 Months | 28 Participants |
| Placebo | Progression-free Survival (PFS) Rate at 3 Months | 12 Participants |
Secondary
Disease of Response (DOR)
Number of patients showing Complete Response (CR), Partial Response (PR) or Stable Disease (SD) based on RECIST for the best response. Number of patients showing Complete Response (CR, disappearance of all target lesions), Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) or Stable Disease (SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum longest diameter since the treatment started) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response
Time frame: Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vandetanib | Disease of Response (DOR) | 33 Participants |
| Placebo | Disease of Response (DOR) | 17 Participants |
Secondary
Objective Response Rate (ORR)
Number of patients showing Complete Response (CR) or Partial Response (PR) based on RECIST for the best response. Number of patients showing Complete Response (CR, disappearance of all target lesions) or Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response.
Time frame: Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vandetanib | Objective Response Rate (ORR) | 14 Participants |
| Placebo | Objective Response Rate (ORR) | 1 Participants |
Secondary
Overall Survival (OS)
Overall survival (OS) defined as the median time from randomization to death from any cause.
Time frame: Every 12 weeks unless the patient withdraws consent
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vandetanib | Overall Survival (OS) | 15.6 months |
| Placebo | Overall Survival (OS) | 20.8 months |
Secondary
Progression-free Survival (PFS)
Progression-free survival (PFS) defined as the median time from randomization to death from any cause or first observed disease progression.
Time frame: Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vandetanib | Progression-free Survival (PFS) | 2.7 months |
| Placebo | Progression-free Survival (PFS) | 1.7 months |