A Phase 2 interventional study of pazopanib and pemetrexed in Lung Cancer, Small Cell, sponsored by GlaxoSmithKline. Terminated at 25 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-10-27.
Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment
This is a Phase II, randomized, open-label, multi-center study in advanced (Stage IVA and IVB subjects per the International Association for the Study of Lung Cancer (IASLC) 2009 Lung cancer staging schema) non-squamous NSCLC subjects comparing pazopanib relative to pemetrexed in the maintenance setting. Subjects should have completed 4-6 cycles of induction therapy with carboplatin + pemetrexed or cisplatin + pemetrexed and have had Stable Disease (SD), Partial Response (PR) or Complete Response (CR) as the best response to be enrolled into the study. The primary objective is to estimate the hazard ratio of progression free survival (PFS) in advanced NSCLC subjects given maintenance therapy of pazopanib (Arm A) relative to pemetrexed (Arm B). The secondary objectives are: overall survival, response rates, safety and tolerability. A total of approximately 200 subjects will be enrolled and randomized in a 1:1 ratio. Safety and efficacy assessments will be regularly performed on all subjects.
7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.
This study's enrollment of 20 is below the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.
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Exclusion Criteria:
Malabsorption syndrome Major resection of the stomach or small bowel
Cardiac angioplasty or stenting Myocardial infarction Unstable angina Coronary artery bypass graft surgery Symptomatic peripheral vascular disease Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).
Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure (BP) must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be \<140/90 mmHg in order for a subject to be eligible for the study.
naproxen, piroxicam, diflusinal, nabumetone, rofecoxib, or celecoxib) it should not be taken 5 days before, the day of, and 2 days after the dose of pemetrexed.
radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
oral agent, administered at 800 mg daily (400 mg tablets x 2). Dose can be reduced, interrupted or discontinued due to adverse events or intolerance
Drug: pazopanib
pemetrexed IV 500 mg/m2 once every 3 weeks
Drug: pemetrexed
oral agent, administered at 800 mg daily (400 mg tablets x 2). Dose can be reduced, interrupted or discontinued due to adverse events or intolerance
pemetrexed IV 500 mg/m2 once every 3 weeks
Progression Free Survival (PFS)
PFS is defined as the interval between the date of randomization and the first documented sign of investigator-assessed (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1) disease progression (PD) or death, whichever occurs first. The date of documented PD is the date of lesion evaluation in the case of radiological PD and the date of symptomatic cancer progression in the case of symptomatic progression (radiological confirmation is required). PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. If the participant received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was to be censored at the last adequate assessment (LAA) prior to the initiation of therapy. Otherwise, if the participant did not have a documented date of progression or death, PFS was to be censored at the date of the LAA.
Time frame: From randomization until the first documented sign of investigator-assessed disease progression or death, whichever occurred first (average of 10 study weeks)
Overall Survival
Overall survival is defined as the interval between the date of randomization and the date of death from any cause.
Time frame: From randomization until disease progression or death (up to Study Week 78)
Number of Participants (Par.) With the Indicated Best Overall Response
A par. was defined as a responder if s/he sustained a CR (The disappearance of all target lesions. Any pathological lymph node must be less than 10 millimeters \[mm\] in the short axis) or PR (At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters) that was confirmed after \>=28 days. Response was evaluated by an investigator per RECIST, version 1.1. A par. without a post-Baseline assessment was considered a non-responder. Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started). To qualify as a best response of SD, a response of SD had to be observed \>=12 weeks after randomization. A par. who was not evaluable had no scans at all or did not have a confirmatory scan.
Time frame: From randomization until the time of the first documented evidence of a confirmed complete response (CR) or partial response (PR) (average of 10 weeks)
Number of Participants With Any Non-serious On-therapy Adverse Event (AE: Occurring in >=5% Participants in Any Treatment Arm) and Serious Adverse Event (SAE)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. In addition, all Grade 4 laboratory abnormalities and other medically important events that require medical or surgical intervention to prevent one of the outcomes listed previously are considered to be SAEs. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Time frame: From the time the first dose of study treatment was administered until 28 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (up to Study Week 55)
Time on Study Treatment (Pazopanib), as a Measure of Extent of Exposure
Time on study treatment, as a measure of extent of exposure, was assessed in all participants who received pazopanib. Time on study treatment was not measured in participants receiving pemetrexed. For these participants, extent of exposure was measured as the mean number of dosing cycles and dose intensity. See the outcome measures entitled "Mean number of dosing cycles, as a measure of extent of exposure" and "Average dose of pemetrexed for all cycles, as a measure of extent of exposure," respectively, for pemetrexed data.
Time frame: From the first day to the last day of treatment (average of 8 weeks)
Mean Daily Dose, as a Measure of Extent of Exposure
Mean daily dose, as a measure of extent of exposure, was assessed in all participants who received pazopanib. Mean daily dose was not measured in participants receiving pemetrexed. For these participants, extent of exposure was measured as the mean number of dosing cycles and dose intensity. See the outcome measures entitled "Mean number of dosing cycles, as a measure of extent of exposure" and "Average dose of pemetrexed for all cycles, as a measure of extent of exposure," respectively, for pemetrexed data.
Time frame: From the first day to the last day of treatment (average of 8 weeks)
Mean Number of Pemetrexed Dosing Cycles, as a Measure of Extent of Exposure
Duration of therapy/time on study treatment, measured as the mean number of pemetrexed dosing cycles as a measure of extent of exposure, was assessed in all participants who received pemetrexed. The mean number of dosing cycles was not measured in participants receiving pazopanib. For these participants, extent of exposure was measured as the time on study treatment and mean daily dose. See the outcome measures entitled "Time on study treatment (pazopanib), as a measure of extent of exposure" and "Mean daily dose, as a measure of extent of exposure," respectively, for pazopanib data.
Time frame: From the time the first dose of study treatment was administered until discontinuation of the study or death (average of 16 weeks)
Average Dose of Pemetrexed for All Cycles, as a Measure of Extent of Exposure
The average dose of pemetrexed for all cycles, as a measure of extent of exposure, was assessed in all participants who received pemetrexed. The average dose was not measured in participants receiving pazopanib. For these participants, extent of exposure was measured as the time on study treatment and mean daily dose. See the outcome measures entitled "Time on study treatment (pazopanib), as a measure of extent of exposure" and "Mean daily dose, as a measure of extent of exposure," respectively, for pazopanib data.
Time frame: From the time the first dose of study treatment was administered until discontinuation of the study or death (average of 16 weeks)
Number of Participants With Any AE (Serious or Non-serious) Leading to Withdrawal From Study Treatment
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. In addition, all Grade 4 laboratory abnormalities and other medically important events that require medical or surgical intervention to prevent one of the outcomes listed previously are considered to be SAEs. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. A participant cold have been withdrawn fom study treatment due to an SAE or AE.
Time frame: From the time the first dose of study treatment was administered until withdrawal from study treatment (up to Study Week 55)
Number of Participants With Any On-therapy AE (Serious or Non-serious) Leading to Dose Reductions (DRs) or Interruptions/Delays in the Study
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. In addition, all Grade 4 laboratory abnormalities and other medically important events that require medical or surgical intervention to prevent one of the outcomes listed previously are considered to be SAEs. Refer to the general Adverse AE/SAE module for a complete list of AEs/SAEs. Management of AEs may require DRs/interruptions in study treatment. If necessary, the pazopanib dose should be reduced stepwise by 200 mg at each step. DRs for pemetrexed were 50-75% of prior dose based on the toxicity leading to DR.
Time frame: From the time the first dose of study treatment was administered until discontinuation of treatment (up to Study Week 55)
Number of Participants With the Indicated Worst-case Change From Baseline in Blood Pressure
Systolic and diastolic blood pressure (BP) were measured. Categories correspond to the following Common Terminology Criteria for Adverse Events (CTCAE) grades: normal, \<120/80 millimeters of mercury (mmHg); prehypertension, 120-139/80-89 mmHg, warranting intervention in participants with high risk; stage I hypertension, 140-159/90-99 mmHg, warranting intervention; and stage II hypertension \>/=160/100, warranting immediate attentive intervention to prevent acute symptoms. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Participants with a missing Baseline value were assumed to have a Baseline value of \<120 for systolic BP (SBP) and \<80 for diastolic BP (DBP).
Time frame: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)
Number of Participants With a Increase From Baseline in Bazett's QTc at the Indicated Time Points
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In clinical studies with pazopanib, events of QT prolongation have occurred.
Time frame: Baseline; Week 6; Week 15; every 9 weeks in the first 6 months; every 12 weeks in the next 6 months; and, after 1 year, every 6 months (up to Study Week 55)
Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Clinical Laboratory Parameters
Hematology and clinical chemistry data were summarized according to National Cancer Institutes (NCI) CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe; Grade 4, Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline grades were assumed to have a Baseline grade of 0. Lymphocyte count increased: Grade 3, \<500 - 200/millimeters cubed (mm\^3); \<0.5 - 0.2x 10e9/Liters (L); Grade 4, \<200/mm\^3; \<0.2x 10e9/L. Lymphocyte count decreased: Grade 3, \>20000/mm\^3; Grade 4, NA. Hyperglycemia; Grade 3, \>250 - 500 milligrams per deciliter (mg/dL); \>13.9 - 27.8 millimoles per Liter (mmol/L); hospitalization indicated; Grade 4, \>500 mg/dL; \>27.8 mmol/L; life-threatening consequences. Hypophosphatemia (inorganic phosphorus): Grade 3, \<2.0 - 1.0 mg/dL, \<0.6 - 0.3 mmol/L; Grade 4, \<1.0 mg/dL, \<0.3 mmol/L, life-threatening consequences.
Time frame: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)
Number of Participants With the Indicated Grade Changes From Baseline Grade in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk. Phos.), and Total Bilirubin (TB)
The laboratory parameters AST, ALT, Alk. Phos., and TB were summarized according to NCI CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe; Grade 4, Life-threatening or disabling; Grade 5, Death. Data are presented for any grade increase, increase to Grade 3, and increase to Grade 4. Participants with missing Baseline grades were assumed to have a Baseline grade of 0. AST/ALT: Grade 1, \>upper limit of normal (ULN) - 3.0x ULN; Grade 2, \>3.0 to 5.0x ULN; Grade 3, \>5.0 - 20.0x ULN; Grade 4, \>20.0x ULN; Grade 5, not available (NA). Alk. Phos.: Grade 1, \>ULN - 2.5x ULN; Grade 2, \>2.5 - 5.0x ULN; Grade 3, \>5.0 - 20.0x ULN; Grade 4, \>20.0x ULN; Grade 5, NA. TB: Grade 1, \>ULN - \>1.5x ULN; Grade 2, \>1.5 - 3.0x ULN; Grade 3, \>3.0 - 10.0x ULN; Grade 4, \>10.0x ULN; Grade 5, NA.
Time frame: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)
Number of Participants With the Indicated Changes From Baseline Value in Lactate Dehydrogenase (LDH)
Change from Baseline in the laboratory parameter LDH was assessed as "decrease to low," "change to normal" of "no change," and "increase to high." Participants with missing Baseline values were assumed to have a normal Baseline value. There is no standard normal range for LDH.
Time frame: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)
| Milestone | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Started | 9 | 11 |
| Completed | 5 | 3 |
| Not completed | 4 | 8 |
| Withdrew: Study closed/terminated | 2 | 4 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Physician decision | 0 | 2 |
| Withdrew: Withdrawal by subject | 2 | 1 |
PFS is defined as the interval between the date of randomization and the first documented sign of investigator-assessed (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1) disease progression (PD) or death, whichever occurs first. The date of documented PD is the date of lesion evaluation in the case of radiological PD and the date of symptomatic cancer progression in the case of symptomatic progression (radiological confirmation is required). PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. If the participant received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was to be censored at the last adequate assessment (LAA) prior to the initiation of therapy. Otherwise, if the participant did not have a documented date of progression or death, PFS was to be censored at the date of the LAA.
| weeks | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Progression Free Survival (PFS) | 10.3 (5.3 to NA) | 12.7 (6.0 to NA) |
Overall survival is defined as the interval between the date of randomization and the date of death from any cause.
No measurements were reported for this outcome.
A par. was defined as a responder if s/he sustained a CR (The disappearance of all target lesions. Any pathological lymph node must be less than 10 millimeters \[mm\] in the short axis) or PR (At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters) that was confirmed after \>=28 days. Response was evaluated by an investigator per RECIST, version 1.1. A par. without a post-Baseline assessment was considered a non-responder. Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started). To qualify as a best response of SD, a response of SD had to be observed \>=12 weeks after randomization. A par. who was not evaluable had no scans at all or did not have a confirmatory scan.
| participants | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| CR | 0 | 0 |
| PR | 0 | 0 |
| SD | 2 | 2 |
| PD | 4 | 4 |
| Not evaluable | 3 | 5 |
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. In addition, all Grade 4 laboratory abnormalities and other medically important events that require medical or surgical intervention to prevent one of the outcomes listed previously are considered to be SAEs. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
| participants | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Non-serious AEs | 9 | 9 |
| SAEs | 2 | 2 |
Time on study treatment, as a measure of extent of exposure, was assessed in all participants who received pazopanib. Time on study treatment was not measured in participants receiving pemetrexed. For these participants, extent of exposure was measured as the mean number of dosing cycles and dose intensity. See the outcome measures entitled "Mean number of dosing cycles, as a measure of extent of exposure" and "Average dose of pemetrexed for all cycles, as a measure of extent of exposure," respectively, for pemetrexed data.
| months | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Time on Study Treatment (Pazopanib), as a Measure of Extent of Exposure | — | 1.8 ± 1.02 |
Mean daily dose, as a measure of extent of exposure, was assessed in all participants who received pazopanib. Mean daily dose was not measured in participants receiving pemetrexed. For these participants, extent of exposure was measured as the mean number of dosing cycles and dose intensity. See the outcome measures entitled "Mean number of dosing cycles, as a measure of extent of exposure" and "Average dose of pemetrexed for all cycles, as a measure of extent of exposure," respectively, for pemetrexed data.
| milligrams | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Mean Daily Dose, as a Measure of Extent of Exposure | — | 751.3 ± 82.85 |
Duration of therapy/time on study treatment, measured as the mean number of pemetrexed dosing cycles as a measure of extent of exposure, was assessed in all participants who received pemetrexed. The mean number of dosing cycles was not measured in participants receiving pazopanib. For these participants, extent of exposure was measured as the time on study treatment and mean daily dose. See the outcome measures entitled "Time on study treatment (pazopanib), as a measure of extent of exposure" and "Mean daily dose, as a measure of extent of exposure," respectively, for pazopanib data.
| number of cycles | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Mean Number of Pemetrexed Dosing Cycles, as a Measure of Extent of Exposure | 5.2 ± 5.49 | — |
The average dose of pemetrexed for all cycles, as a measure of extent of exposure, was assessed in all participants who received pemetrexed. The average dose was not measured in participants receiving pazopanib. For these participants, extent of exposure was measured as the time on study treatment and mean daily dose. See the outcome measures entitled "Time on study treatment (pazopanib), as a measure of extent of exposure" and "Mean daily dose, as a measure of extent of exposure," respectively, for pazopanib data.
| milligrams per meters squared (m^2) | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Average Dose of Pemetrexed for All Cycles, as a Measure of Extent of Exposure | 499.54 ± 30.222 | — |
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. In addition, all Grade 4 laboratory abnormalities and other medically important events that require medical or surgical intervention to prevent one of the outcomes listed previously are considered to be SAEs. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. A participant cold have been withdrawn fom study treatment due to an SAE or AE.
| participants | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Number of Participants With Any AE (Serious or Non-serious) Leading to Withdrawal From Study Treatment | 2 | 2 |
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. In addition, all Grade 4 laboratory abnormalities and other medically important events that require medical or surgical intervention to prevent one of the outcomes listed previously are considered to be SAEs. Refer to the general Adverse AE/SAE module for a complete list of AEs/SAEs. Management of AEs may require DRs/interruptions in study treatment. If necessary, the pazopanib dose should be reduced stepwise by 200 mg at each step. DRs for pemetrexed were 50-75% of prior dose based on the toxicity leading to DR.
| participants | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Dose reductions | 1 | 2 |
| Dose interruptions/delays | 1 | 3 |
Systolic and diastolic blood pressure (BP) were measured. Categories correspond to the following Common Terminology Criteria for Adverse Events (CTCAE) grades: normal, \<120/80 millimeters of mercury (mmHg); prehypertension, 120-139/80-89 mmHg, warranting intervention in participants with high risk; stage I hypertension, 140-159/90-99 mmHg, warranting intervention; and stage II hypertension \>/=160/100, warranting immediate attentive intervention to prevent acute symptoms. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Participants with a missing Baseline value were assumed to have a Baseline value of \<120 for systolic BP (SBP) and \<80 for diastolic BP (DBP).
| participants | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| SBP, increase to 120-139 mmHg | 2 | 1 |
| SBP, increase to 140-159 mmHg | 3 | 3 |
| SBP, increase to >=160 mmHg | 1 | 4 |
| DBP, increase to 80-89 mmHg | 2 | 3 |
| DBP, increase to 90-99 mmHg | 1 | 5 |
| DBP, increase to >=100 mmHg | 0 | 0 |
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In clinical studies with pazopanib, events of QT prolongation have occurred.
| participants | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Number of Participants With a Increase From Baseline in Bazett's QTc at the Indicated Time Points | 0 | 0 |
Hematology and clinical chemistry data were summarized according to National Cancer Institutes (NCI) CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe; Grade 4, Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline grades were assumed to have a Baseline grade of 0. Lymphocyte count increased: Grade 3, \<500 - 200/millimeters cubed (mm\^3); \<0.5 - 0.2x 10e9/Liters (L); Grade 4, \<200/mm\^3; \<0.2x 10e9/L. Lymphocyte count decreased: Grade 3, \>20000/mm\^3; Grade 4, NA. Hyperglycemia; Grade 3, \>250 - 500 milligrams per deciliter (mg/dL); \>13.9 - 27.8 millimoles per Liter (mmol/L); hospitalization indicated; Grade 4, \>500 mg/dL; \>27.8 mmol/L; life-threatening consequences. Hypophosphatemia (inorganic phosphorus): Grade 3, \<2.0 - 1.0 mg/dL, \<0.6 - 0.3 mmol/L; Grade 4, \<1.0 mg/dL, \<0.3 mmol/L, life-threatening consequences.
| participants | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Lymphocytes, Grade 3 | 2 | 1 |
| Hyperglycemia, Grade 3 | 0 | 1 |
| Phosphorus inorganic, Grade 3 | 0 | 1 |
The laboratory parameters AST, ALT, Alk. Phos., and TB were summarized according to NCI CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe; Grade 4, Life-threatening or disabling; Grade 5, Death. Data are presented for any grade increase, increase to Grade 3, and increase to Grade 4. Participants with missing Baseline grades were assumed to have a Baseline grade of 0. AST/ALT: Grade 1, \>upper limit of normal (ULN) - 3.0x ULN; Grade 2, \>3.0 to 5.0x ULN; Grade 3, \>5.0 - 20.0x ULN; Grade 4, \>20.0x ULN; Grade 5, not available (NA). Alk. Phos.: Grade 1, \>ULN - 2.5x ULN; Grade 2, \>2.5 - 5.0x ULN; Grade 3, \>5.0 - 20.0x ULN; Grade 4, \>20.0x ULN; Grade 5, NA. TB: Grade 1, \>ULN - \>1.5x ULN; Grade 2, \>1.5 - 3.0x ULN; Grade 3, \>3.0 - 10.0x ULN; Grade 4, \>10.0x ULN; Grade 5, NA.
| participants | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| AST, any Grade | 1 | 0 |
| AST, Grade 3 | 0 | 0 |
| AST, Grade 4 | 0 | 0 |
| ALT, any Grade | 1 | 1 |
| ALT, Grade 3 | 0 | 0 |
| ALT, Grade 4 | 0 | 0 |
| Alk. Phos., any Grade | 0 | 1 |
| Alk. Phos., Grade 3 | 0 | 0 |
| Alk. Phos., Grade 4 | 0 | 0 |
| TB, any Grade | 0 | 0 |
| TB, Grade 3 | 0 | 0 |
| TB, Grade 4 | 0 | 0 |
Change from Baseline in the laboratory parameter LDH was assessed as "decrease to low," "change to normal" of "no change," and "increase to high." Participants with missing Baseline values were assumed to have a normal Baseline value. There is no standard normal range for LDH.
| participants | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Decrease to low | 0 | 0 |
| Change to normal/No change | 4 | 7 |
| Increase to high | 5 | 3 |
Collected over Participants were analyzed from the time the first dose of study treatment was administered until 28 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (up to Study Week 55).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Pemetrexed 500 mg/m^2 | — | 2/9 (22.2%) | 9/9 (100%) |
| Pazopanib 800 mg | — | 2/10 (20%) | 9/10 (90%) |
| Event | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 1/9 | 0/10 |
| Chest painGeneral disorders | 1/9 | 0/10 |
| PneumoniaInfections and infestations | 1/9 | 0/10 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/9 | 1/10 |
| Pneumothorax traumaticInjury, poisoning and procedural complications | 0/9 | 1/10 |
| Event | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg |
|---|---|---|
| FatigueGeneral disorders | 3/9 | 3/10 |
| NauseaGastrointestinal disorders | 2/9 | 3/10 |
| Alanine aminotransferase increasedInvestigations | 0/9 | 3/10 |
| Aspartate aminotransferase increasedInvestigations | 0/9 | 3/10 |
| DiarrhoeaGastrointestinal disorders | 0/9 | 3/10 |
| CoughRespiratory, thoracic and mediastinal disorders | 2/9 | 2/10 |
| Decreased appetiteMetabolism and nutrition disorders | 2/9 | 1/10 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 2/9 | 1/10 |
| AnaemiaBlood and lymphatic system disorders | 2/9 | 0/10 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 2/9 | 0/10 |
| Age, Continuous(Years) | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg | Total |
|---|---|---|---|
| Mean | 71.1 ± 12.09 | 72.6 ± 11.81 | 72.0 ± 11.64 |
| Sex: Female, Male(Participants) | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg | Total |
|---|---|---|---|
| Female | 2 | 7 | 9 |
| Male | 7 | 4 | 11 |
| Race/Ethnicity, Customized(Participants) | Pemetrexed 500 mg/m^2 | Pazopanib 800 mg | Total |
|---|---|---|---|
| White - White/Caucasian/European Heritage | 9 | 10 | 19 |
| Missing | 0 | 1 | 1 |
This study is terminated, as verified in Oct 2013. You cannot join it, but the record below documents what was studied.
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GlaxoSmithKline