Carcinoma, Non-Small-Cell Lung (NSCLC)
Conditions
Keywords
AG-013736, axitinib, cisplatin, gemcitabine, NSCLC, squamous cell, lung cancer
Brief summary
This study will evaluate whether AG-013736 when combined with cisplatin and gemcitabine shows activity and is safe in patients with squamous type of non-small cell lung cancer
Interventions
DRUGAG-013736
AG-013736 5 mg tablets orally, twice daily, until disease progression
DRUGgemcitabine
200-mg or 1 g lyophilized powder, to be administered as 1250 mg/m\^2 IV infusion on Day 1 and Day 8 of 21-day cycle. For a maximum of 6 cycles
DRUGcisplatin
1mg/ml solution or as lyophilized powder, to be administered as 80 mg/m\^2 IV infusion on Day 1 of 21-day cycle. For a maximum of 6 cycles
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically- or cytologically-confirmed diagnosis of squamous NSCLC Stage IIIB with malignant effusion (fluid cytology demonstrating malignant cells required), Stage IV, or recurrent disease after definitive local therapy * Candidate for primary treatment with cisplatin and gemcitabine * Presence of measurable disease by RECIST * Adequate organ function as defined by the following criteria: ECOG performance status of 0 or 1
Exclusion criteria
* Prior systemic treatment for Stage IIIB (with malignant effusion) or Stage IV NSCLC. * One or more lung lesions with cavitation, or any lesion invading or abutting a major blood vessel as assessed by CT or MRI. * History of hemoptysis \> ½ tsp (2.5 ml) of blood per day for a day or more within 1 week of study treatment, or Grade 3 or 4 hemoptysis within 4 weeks of study treatment * NCI CTCAE Grade 3 hemorrhage from any cause within 4 weeks of study treatment * Preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. * Untreated brain metastases. * Need for therapeutic anticoagulation, regular use of aspirin (\> 325 mg/day), NSAID or other medications known to inhibit platelet function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR) | Baseline until disease progression or discontinuation from the study due to any cause, assessed every 6 weeks during chemotherapy phase and every 8 weeks during single agent phase up to final study visit (Week 78) | Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are those with disappearance of all target lesions. PR are those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Baseline until death or assessed every 2 months (up to 28 days after the last dose) | Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). |
| Progression Free Survival (PFS) | Baseline, assessed every 2 months (up to 28 days after the last dose) | Time in months from start of study treatment to the first documentation of objective tumor progression or to death due to any cause. PFS calculated as (Months) = (first event date minus first dose date plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was Death). |
| Duration of Response (DR) | Baseline until disease progression or discontinuation from the study due to any cause, assessed every 6 weeks during chemotherapy phase and every 8 weeks during single agent phase up to final study visit (Week 78) | Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response. |
Countries
Poland, Romania, South Africa, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Axitinib + Cisplatin + Gemcitabine Axitinib (AG-013736) tablet 5 milligram (mg) starting dose orally twice daily continuously along with cisplatin 80 mg per square meter (mg/m\^2) intravenous 2 hours infusion on day 1 of each cycle and gemcitabine 1250 mg/m\^2 intravenous 30 minutes infusion on days 1 and 8 of each cycle up to 6 cycles (cycle length 21 days), in chemotherapy phase. Axitinib (AG-013736) tablet 5 mg orally twice daily continuously up to 15 cycles (cycle length 28 days), in single agent phase. | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 20 |
| Overall Study | Other | 8 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Study Terminated by Sponsor | 5 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Axitinib + Cisplatin + Gemcitabine |
|---|---|
| Age Continuous | 60.5 Years STANDARD_DEVIATION 7.1 |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 38 |
| serious Total, serious adverse events | 15 / 38 |
Outcome results
Primary
Percentage of Participants With Objective Response (OR)
Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are those with disappearance of all target lesions. PR are those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions.
Time frame: Baseline until disease progression or discontinuation from the study due to any cause, assessed every 6 weeks during chemotherapy phase and every 8 weeks during single agent phase up to final study visit (Week 78)
Population: Intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Axitinib + Cisplatin + Gemcitabine | Percentage of Participants With Objective Response (OR) | 39.5 Percentage of participants |
Secondary
Duration of Response (DR)
Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time frame: Baseline until disease progression or discontinuation from the study due to any cause, assessed every 6 weeks during chemotherapy phase and every 8 weeks during single agent phase up to final study visit (Week 78)
Population: DR was calculated for the subgroup of participants from the ITT set, with a confirmed objective tumor response (CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + Cisplatin + Gemcitabine | Duration of Response (DR) | 5.78 Months |
Secondary
Overall Survival (OS)
Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Time frame: Baseline until death or assessed every 2 months (up to 28 days after the last dose)
Population: ITT population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + Cisplatin + Gemcitabine | Overall Survival (OS) | 14.2 Months |
Secondary
Progression Free Survival (PFS)
Time in months from start of study treatment to the first documentation of objective tumor progression or to death due to any cause. PFS calculated as (Months) = (first event date minus first dose date plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was Death).
Time frame: Baseline, assessed every 2 months (up to 28 days after the last dose)
Population: ITT population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + Cisplatin + Gemcitabine | Progression Free Survival (PFS) | 6.2 Months |