Trial Outcomes & Findings for A Study to Evaluate Pazopanib in Comparison to Pemetrexed in Maintenance Setting in Non-progressing Subjects With Metastatic Stage IVA and IVB Non-squamous Non-small Cell Lung Cancer (NSCLC) Population (NCT NCT01313663)

Last Updated: 2014-10-27

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

From randomization until the first documented sign of investigator-assessed disease progression or death, whichever occurred first (average of 10 study weeks)

Results posted on

2014-10-27

Participant Flow

Participants (par.) must have received at least 4-6 cycles of induction therapy with carboplatin + pemetrexed or cisplatin + pemetrexed and should have had stable disease, partial response, or complete response as best response at the time of screening/enrollment. Par. were stratified by disease stage and cycles of induction therapy at enrollment.

Participant milestones

Participant milestones
Measure	Pemetrexed 500 mg/m^2 Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Overall Study STARTED	9	11
Overall Study COMPLETED	5	3
Overall Study NOT COMPLETED	4	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Pemetrexed 500 mg/m^2 Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Overall Study Study Closed/Terminated	2	4
Overall Study Lost to Follow-up	0	1
Overall Study Physician Decision	0	2
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

A Study to Evaluate Pazopanib in Comparison to Pemetrexed in Maintenance Setting in Non-progressing Subjects With Metastatic Stage IVA and IVB Non-squamous Non-small Cell Lung Cancer (NSCLC) Population

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=11 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Total n=20 Participants Total of all reporting groups
Age, Continuous	71.1 Years STANDARD_DEVIATION 12.09 • n=5 Participants	72.6 Years STANDARD_DEVIATION 11.81 • n=7 Participants	72.0 Years STANDARD_DEVIATION 11.64 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until the first documented sign of investigator-assessed disease progression or death, whichever occurred first (average of 10 study weeks)

Population: Intent-to-Treat (ITT) Population: all participants who were randomized to study treatment regardless of whether or not treatment was administered

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=11 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Progression Free Survival (PFS)	10.3 weeks Interval 5.3 to There were too few events of progression/death to calculate the upper limit (UL) of the confidence interval (CI).	12.7 weeks Interval 6.0 to There were too few events of progression/death to calculate the upper limit (UL) of the confidence interval (CI).

SECONDARY outcome

Timeframe: From randomization until disease progression or death (up to Study Week 78)

Population: The study size (20 participants) and follow up were not adequate to assess overall survival. Participants who had not died at the time of the cut-off for the analysis were to be censored at the date the particpant was last known to be alive.

Overall survival is defined as the interval between the date of randomization and the date of death from any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From randomization until the time of the first documented evidence of a confirmed complete response (CR) or partial response (PR) (average of 10 weeks)

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=11 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Number of Participants (Par.) With the Indicated Best Overall Response CR	0 participants	0 participants
Number of Participants (Par.) With the Indicated Best Overall Response PR	0 participants	0 participants
Number of Participants (Par.) With the Indicated Best Overall Response PD	4 participants	4 participants
Number of Participants (Par.) With the Indicated Best Overall Response Not evaluable	3 participants	5 participants
Number of Participants (Par.) With the Indicated Best Overall Response SD	2 participants	2 participants

SECONDARY outcome

Timeframe: 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)

Population: Safety Population: all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.

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.

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=10 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
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) Non-serious AEs	9 participants	9 participants
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) SAEs	2 participants	2 participants

SECONDARY outcome

Timeframe: From the first day to the last day of treatment (average of 8 weeks)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=10 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Time on Study Treatment (Pazopanib), as a Measure of Extent of Exposure	—	1.8 months Standard Deviation 1.02

SECONDARY outcome

Timeframe: From the first day to the last day of treatment (average of 8 weeks)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=10 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Mean Daily Dose, as a Measure of Extent of Exposure	—	751.3 milligrams Standard Deviation 82.85

SECONDARY outcome

Timeframe: From the time the first dose of study treatment was administered until discontinuation of the study or death (average of 16 weeks)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Mean Number of Pemetrexed Dosing Cycles, as a Measure of Extent of Exposure	5.2 number of cycles Standard Deviation 5.49	—

SECONDARY outcome

Timeframe: From the time the first dose of study treatment was administered until discontinuation of the study or death (average of 16 weeks)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Average Dose of Pemetrexed for All Cycles, as a Measure of Extent of Exposure	499.54 milligrams per meters squared (m^2) Standard Deviation 30.222	—

SECONDARY outcome

Timeframe: From the time the first dose of study treatment was administered until withdrawal from study treatment (up to Study Week 55)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=10 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Number of Participants With Any AE (Serious or Non-serious) Leading to Withdrawal From Study Treatment	2 participants	2 participants

SECONDARY outcome

Timeframe: From the time the first dose of study treatment was administered until discontinuation of treatment (up to Study Week 55)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=10 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Number of Participants With Any On-therapy AE (Serious or Non-serious) Leading to Dose Reductions (DRs) or Interruptions/Delays in the Study Dose reductions	1 participants	2 participants
Number of Participants With Any On-therapy AE (Serious or Non-serious) Leading to Dose Reductions (DRs) or Interruptions/Delays in the Study Dose interruptions/delays	1 participants	3 participants

SECONDARY outcome

Timeframe: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)

Population: Safety Population

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).

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=10 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Number of Participants With the Indicated Worst-case Change From Baseline in Blood Pressure SBP, increase to 120-139 mmHg	2 participants	1 participants
Number of Participants With the Indicated Worst-case Change From Baseline in Blood Pressure SBP, increase to 140-159 mmHg	3 participants	3 participants
Number of Participants With the Indicated Worst-case Change From Baseline in Blood Pressure DBP, increase to 90-99 mmHg	1 participants	5 participants
Number of Participants With the Indicated Worst-case Change From Baseline in Blood Pressure DBP, increase to >=100 mmHg	0 participants	0 participants
Number of Participants With the Indicated Worst-case Change From Baseline in Blood Pressure SBP, increase to >=160 mmHg	1 participants	4 participants
Number of Participants With the Indicated Worst-case Change From Baseline in Blood Pressure DBP, increase to 80-89 mmHg	2 participants	3 participants

SECONDARY outcome

Timeframe: 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)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=10 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Number of Participants With a Increase From Baseline in Bazett's QTc at the Indicated Time Points	0 participants	0 participants

SECONDARY outcome

Timeframe: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=10 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Clinical Laboratory Parameters Lymphocytes, Grade 3	2 participants	1 participants
Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Clinical Laboratory Parameters Phosphorus inorganic, Grade 3	0 participants	1 participants
Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Clinical Laboratory Parameters Hyperglycemia, Grade 3	0 participants	1 participants

SECONDARY outcome

Timeframe: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=10 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
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) AST, Grade 3	0 participants	0 participants
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) ALT, Grade 4	0 participants	0 participants
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) AST, any Grade	1 participants	0 participants
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) AST, Grade 4	0 participants	0 participants
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) ALT, any Grade	1 participants	1 participants
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) ALT, Grade 3	0 participants	0 participants
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) Alk. Phos., any Grade	0 participants	1 participants
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) Alk. Phos., Grade 3	0 participants	0 participants
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) Alk. Phos., Grade 4	0 participants	0 participants
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) TB, any Grade	0 participants	0 participants
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) TB, Grade 3	0 participants	0 participants
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) TB, Grade 4	0 participants	0 participants

SECONDARY outcome

Timeframe: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Pemetrexed 500 mg/m^2 n=9 Participants Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=10 Participants Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Number of Participants With the Indicated Changes From Baseline Value in Lactate Dehydrogenase (LDH) Decrease to low	0 participants	0 participants
Number of Participants With the Indicated Changes From Baseline Value in Lactate Dehydrogenase (LDH) Change to normal/No change	4 participants	7 participants
Number of Participants With the Indicated Changes From Baseline Value in Lactate Dehydrogenase (LDH) Increase to high	5 participants	3 participants

Adverse Events

Pemetrexed 500 mg/m^2

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Pazopanib 800 mg

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pemetrexed 500 mg/m^2 n=9 participants at risk Participants received an intravenous (IV) infusion of pemetrexed (500 mg per meters squared \[mg/m\^2\]) over 10 minutes on Day 1 of each 21-day cycle. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.	Pazopanib 800 mg n=10 participants at risk Participants received pazopanib 800 milligrams (mg) orally once a day at approximately the same time each day, either 1 hour before a meal or 2 hours after a meal. The tablets were to be swallowed whole and were not to be crushed or broken. Participants received study treatment until disease progression, death, unacceptable adverse event, withdrawal of consent, or physician decision. Participants who withdrew due to an adverse event or disease progression were followed for survival.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/9 • 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). Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprisedof all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.	10.0% 1/10 • 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). Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprisedof all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.
Respiratory, thoracic and mediastinal disorders Respiratory failure	11.1% 1/9 • 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). Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprisedof all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.	0.00% 0/10 • 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). Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprisedof all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.
General disorders Chest pain	11.1% 1/9 • 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). Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprisedof all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.	0.00% 0/10 • 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). Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprisedof all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.
Infections and infestations Pneumonia	11.1% 1/9 • 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). Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprisedof all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.	0.00% 0/10 • 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). Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprisedof all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.
Injury, poisoning and procedural complications Pneumothorax traumatic	0.00% 0/9 • 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). Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprisedof all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.	10.0% 1/10 • 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). Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprisedof all participants who were randomized and took at least one dose of study medication. This population was based on the actual treatment received, if it differed from that to which the participant was randomized.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER