Lung Cancer
Conditions
Keywords
Pazopanib, Non Squamous Non Small Cell Lung Cancer, After Progress on first line therapy, Using Bevacizumab
Brief summary
This is an open label Phase II Trial that using the investigational anti-cancer agent, Pazopanib to see whether non-squamous non-small cell lung cancer will respond to its use by decreasing the size of the tumor or stopping its growth.
Detailed description
This multi-centered phase II trial will examine pazopanib stage IIIB/IV non-squamous NSCLC patients who have progressed on first-line therapy containing bevacizumab. Treatment should continue until disease progression, unacceptable toxicity, study withdrawal, or death. Patients who progress will be treated at the discretion of their physician. all patients who initiate treatment will be evaluated for disease control rate, which is the primary endpoint of this study. The primary objective is to estimate the disease control rate of pazopanib alone in patients with stage IIIB/IV non-squamous NSCLC who progressed while on bevacizumab. Disease control rate id defined as complete (CR) + partial response (PR) + stable disease (SD) lasting greater than or equal to 12 weeks as defined by RECIST. Secondary Objectives To estimate the combined response rate (CR + PR) of pazopanib according to RECIST To estimate the progression free survival (defined as time of enrollment until disease progression or death) and overall survival (defined as time of enrollment until death) of patients treated with pazopanib. To evaluate the safety and tolerability of pazopanib using the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.0 To explore potential correlations between blood biomarkers and clinical response. Pazopanib is dosed continuously throughout the study. Cycle lengths are identified as 21 days for purposes of the calendar. The treatment dosage and administration for participating subjects will be, Pazopanib, 800 mg by mouth daily during a 21 day cycle until disease progression.
Interventions
DRUGPazopanib
Pazopanib, 800 mg by mouth daily each 21 day cycle
Sponsors
GlaxoSmithKline
UNC Lineberger Comprehensive Cancer Center
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
* Age 18 or older * Stage IIIB (with malignant pleural or pericardial effusion or supraclavicular lymph node involvement) or stage IV NSCLC * Evidence of progression while on bevacizumab * Patients treated for CNS metastases who are asymptomatic with no requirement for steroids for 2 weeks prior to first dose of study drug
Exclusion criteria
* Prior malignancy * Clinically significant gastrointestinal abnormalities * Presence of uncontrolled infection or nonhealing wound, fracture, or ulcer * History of cardiovascular conditions within the past 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | Eight (8) months w additional time for response date to mature (up to 2 years per participant) | Response (CR + PR + SD) as defined by RECIST v1.1 lasting equal to or greater than 12 weeks in patients treated with pazopanib alone for stage IIIB/IV non-squamous NSCLC after progression on first line therapy containing bevacizumab Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) : Complete Response (CR) is defined as Disappearance of all target lesions; Partial Response (PR), as a \>=30% decrease in the sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) of all target lesions; Progression, as a 20% increase in the sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) of all target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. Target lesions are representative of all involved organs and measurable by radiographic imaging. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Combined Response Rate (CR + PR) of Pazopanib According to RECIST v1.1 | 8 months with additional time for response to mature (up to 2 years per participant) | Estimate of combined response rate (Complete Response (CR) + Partial Response (PR) per RECIST v1.1 Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) : Complete Response (CR) is defined as the disappearance of all target lesions and Partial Response (PR) as a \>=30% decrease in the sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) of all target lesions.Target lesions are representative of all involved organs and measurable by radiographic imaging. |
| Progression Free Survival | Eight (8) months w additional time for response data to mature (up to 2 years per participant) | Progression free survival is defined as time of enrollment until disease progression or death Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) : Progression is defined as a 20% increase in the sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) of all target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Target lesions are representative of all involved organs and measurable by radiographic imaging. |
| Overall Survival | Eight (8) months w additional time for response date to mature (up to 2 years per participant) | Overall survival is defined as the time of enrollment until death |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited between April 2010 and January 2014
Pre-assignment details
A total of 22 patients provided informed consent for this trial; 7 patients were considered ineligible leaving 15 patients who enrolled and were treated on study.
Participants by arm
| Arm | Count |
|---|---|
| Single Intervention Subjects will take Pazopanib, 800 mg daily by mouth throughout the time in study
Pazopanib: Pazopanib, 800 mg by mouth daily each 21 day cycle | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Drug held for 21+ days | 1 |
| Overall Study | Lack of Efficacy | 9 |
Baseline characteristics
| Characteristic | Single Intervention |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 15 |
| serious Total, serious adverse events | 5 / 15 |
Outcome results
Primary
Disease Control Rate
Response (CR + PR + SD) as defined by RECIST v1.1 lasting equal to or greater than 12 weeks in patients treated with pazopanib alone for stage IIIB/IV non-squamous NSCLC after progression on first line therapy containing bevacizumab Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) : Complete Response (CR) is defined as Disappearance of all target lesions; Partial Response (PR), as a \>=30% decrease in the sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) of all target lesions; Progression, as a 20% increase in the sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) of all target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. Target lesions are representative of all involved organs and measurable by radiographic imaging.
Time frame: Eight (8) months w additional time for response date to mature (up to 2 years per participant)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Intervention | Disease Control Rate | 13 % of participants with disease control |
Secondary
Combined Response Rate (CR + PR) of Pazopanib According to RECIST v1.1
Estimate of combined response rate (Complete Response (CR) + Partial Response (PR) per RECIST v1.1 Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) : Complete Response (CR) is defined as the disappearance of all target lesions and Partial Response (PR) as a \>=30% decrease in the sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) of all target lesions.Target lesions are representative of all involved organs and measurable by radiographic imaging.
Time frame: 8 months with additional time for response to mature (up to 2 years per participant)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Intervention | Combined Response Rate (CR + PR) of Pazopanib According to RECIST v1.1 | 0 participants |
Secondary
Overall Survival
Overall survival is defined as the time of enrollment until death
Time frame: Eight (8) months w additional time for response date to mature (up to 2 years per participant)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Intervention | Overall Survival | 24.1 weeks |
Secondary
Progression Free Survival
Progression free survival is defined as time of enrollment until disease progression or death Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) : Progression is defined as a 20% increase in the sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) of all target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Target lesions are representative of all involved organs and measurable by radiographic imaging.
Time frame: Eight (8) months w additional time for response data to mature (up to 2 years per participant)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Intervention | Progression Free Survival | 10.9 weeks |