Non Small Cell Lung Cancer, Lung Cancer
Conditions
Keywords
NSCLC, Phase II, ZD4054, Pemetrexed, Lung Cancer
Brief summary
The aim of this study is to collect initial efficacy and safety data on the use of a new treatment ZD4054 (Zibotentan) when used in combination with pemetrexed (a standard chemotherapy agent) for the treatment of non-small cell lung cancer compared to treatment with pemetrexed alone
Interventions
DRUGZD4054
10mg oral tablet, once daily
DRUGPemetrexed
500mg2/m IV infusion
DRUGPlacebo
10mg oral tablet, once daily
Sponsors
AstraZeneca
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
* Histologically or cytologically confirmed locally advanced or metastatic NSCLC on entry into study suitable for pemetrexed therapy * Patients that meet one of the following criteria: - progressed following one prior platinum-based chemotherapy regimen for locally advanced or metastatic disease; -progressed within 6 months of adjuvant platinum-based chemotherapy * Life expectancy of \> 12 weeks
Exclusion criteria
* Prior treatment with pemetrexed in the last 12 months. * Prior therapy with an ET receptor antagonist * Any recent surgery, unhealed surgical incision, severe concomitant medical condition (eg, unstable cardiac, hepatic or renal disease) or significant laboratory finding which makes it undesirable for the patient to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Death | Patients were followed up for survival every week for the first 3 weeks then every 3 weeks whilst on study medication until the data cut-off (17th January 2010). | Median time (in days) from randomisation until death using the Kaplan-Meier method (Calculator for survival probability) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Tumour assessments for progression were performed at screening, every 3 weeks, Mandatory Tumour Assessment Visit (19 August 2009 ± 3 days), treatment discontinuation | Median time (in days) from randomisation until disease progression/death using the Kaplan-Meier method |
Countries
Bulgaria, Czechia, France, Romania, Ukraine
Participant flow
Recruitment details
80 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) where the histology was not predominantly of squamous type were recruited between 12th August 2008 and 3rd June 2009.
Pre-assignment details
14 of the 80 enrolled patients were not randomised to treatments groups: 7 patients did not meet one or more of the study inclusion or exclusion criteria, 3 patients failed screening, 2 patients were not included due to investigator decision, 1 patient withdrew consent and 1 patient died.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Pemetrexed Pemetrexed 500 mg/m2 Intravenous (IV) infusion every 21 days + placebo oral tablet once daily | 36 |
| ZD4054 + Pemetrexed ZD4054 10 mg oral tablet once daily + Pemetrexed 500 mg/m2 IV infusion every 21 days | 30 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Continuing study treatment | 4 | 4 |
Baseline characteristics
| Characteristic | Placebo + Pemetrexed | ZD4054 + Pemetrexed | Total |
|---|---|---|---|
| Age Continuous | 56.6 Years STANDARD_DEVIATION 12.06 | 57.5 Years STANDARD_DEVIATION 10.44 | 57 Years STANDARD_DEVIATION 11.25 |
| Sex: Female, Male Female | 8 Participants | 11 Participants | 19 Participants |
| Sex: Female, Male Male | 28 Participants | 19 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 30 | 20 / 36 |
| serious Total, serious adverse events | 7 / 30 | 4 / 36 |
Outcome results
Primary
Time to Death
Median time (in days) from randomisation until death using the Kaplan-Meier method (Calculator for survival probability)
Time frame: Patients were followed up for survival every week for the first 3 weeks then every 3 weeks whilst on study medication until the data cut-off (17th January 2010).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Pemetrexed | Time to Death | 193 Days |
| ZD4054 + Pemetrexed | Time to Death | 146 Days |
Secondary
Progression-free Survival
Median time (in days) from randomisation until disease progression/death using the Kaplan-Meier method
Time frame: Tumour assessments for progression were performed at screening, every 3 weeks, Mandatory Tumour Assessment Visit (19 August 2009 ± 3 days), treatment discontinuation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Pemetrexed | Progression-free Survival | 87 Days |
| ZD4054 + Pemetrexed | Progression-free Survival | 110 Days |