Trial Outcomes & Findings for A Phase II Trial Comparing Gemcitabine and Pazopanib Versus Gemcitabine and Docetaxel for Patients With Advanced Soft Tissue Sarcoma (NCT NCT01593748)

Last Updated: 2020-04-06

Results Overview

To estimate the PFS of the combination of G+P or G+T in patients with metastatic and/or locally advanced or recurrent STS. Progression free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

90 participants

Primary outcome timeframe

minimum of 18 months

Results posted on

2020-04-06

Participant Flow

Participant milestones

Participant milestones
Measure	Experimental Patients in Group 1 will get Gemcitabine 1000 mg/m2 intravenously on Day 1 and Day 8 and Pazopanib 800mg by mouth daily on a 21 day cycle. Cycles will continue until disease progression or patient withdrawal. Gemcitabine and Pazopanib: Gemcitabine 1000 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Pazopanib 800 mg by oral tablet daily for a 21 day cycle.	Standard of Care Patients in Group 2 will get Gemcitabine 900 mg/m2 intravenously on Day 1 and Day 8. Additionally on Day 8, patients will have Docetaxel 100 mg/m2 given intravenously. on a 21 day cycle. If disease progression occurs on this treatment, patients will have the option to receive treatment with Gemcitabine and Pazopanib (group 1). Gemcitabine and Docetaxel: Gemcitabine 900 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Docetaxel 100 mg/m2 by IV on day 8 of a 21 day cycle.
Overall Study STARTED	45	45
Overall Study COMPLETED	45	45
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase II Trial Comparing Gemcitabine and Pazopanib Versus Gemcitabine and Docetaxel for Patients With Advanced Soft Tissue Sarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental n=45 Participants Patients in Group 1 will get Gemcitabine 1000 mg/m2 intravenously on Day 1 and Day 8 and Pazopanib 800mg by mouth daily on a 21 day cycle. Cycles will continue until disease progression or patient withdrawal. Gemcitabine and Pazopanib: Gemcitabine 1000 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Pazopanib 800 mg by oral tablet daily for a 21 day cycle.	Standard of Care n=45 Participants Patients in Group 2 will get Gemcitabine 900 mg/m2 intravenously on Day 1 and Day 8. Additionally on Day 8, patients will have Docetaxel 100 mg/m2 given intravenously. on a 21 day cycle. If disease progression occurs on this treatment, patients will have the option to receive treatment with Gemcitabine and Pazopanib (group 1). Gemcitabine and Docetaxel: Gemcitabine 900 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Docetaxel 100 mg/m2 by IV on day 8 of a 21 day cycle.	Total n=90 Participants Total of all reporting groups
Age, Continuous	57.93 years STANDARD_DEVIATION 13.76 • n=5 Participants	54.6 years STANDARD_DEVIATION 14.10 • n=7 Participants	56.27 years STANDARD_DEVIATION 13.95 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	22 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	23 Participants n=7 Participants	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	43 Participants n=7 Participants	80 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants	33 Participants n=7 Participants	69 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: minimum of 18 months

Outcome measures

Outcome measures
Measure	Experimental n=45 Participants Patients in Group 1 will get Gemcitabine 1000 mg/m2 intravenously on Day 1 and Day 8 and Pazopanib 800mg by mouth daily on a 21 day cycle. Cycles will continue until disease progression or patient withdrawal. Gemcitabine and Pazopanib: Gemcitabine 1000 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Pazopanib 800 mg by oral tablet daily for a 21 day cycle.	Standard of Care n=45 Participants Patients in Group 2 will get Gemcitabine 900 mg/m2 intravenously on Day 1 and Day 8. Additionally on Day 8, patients will have Docetaxel 100 mg/m2 given intravenously. on a 21 day cycle. If disease progression occurs on this treatment, patients will have the option to receive treatment with Gemcitabine and Pazopanib (group 1). Gemcitabine and Docetaxel: Gemcitabine 900 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Docetaxel 100 mg/m2 by IV on day 8 of a 21 day cycle.
Average Number of Months of Progression-free Survival	4.1 months Interval 2.4 to 8.6	4.1 months Interval 2.7 to 11.4

PRIMARY outcome

Timeframe: 30 days post end of treatment

Toxicity is graded according to the CTCAE v 4.

Outcome measures

Outcome measures
Measure	Experimental n=45 Participants Patients in Group 1 will get Gemcitabine 1000 mg/m2 intravenously on Day 1 and Day 8 and Pazopanib 800mg by mouth daily on a 21 day cycle. Cycles will continue until disease progression or patient withdrawal. Gemcitabine and Pazopanib: Gemcitabine 1000 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Pazopanib 800 mg by oral tablet daily for a 21 day cycle.	Standard of Care n=45 Participants Patients in Group 2 will get Gemcitabine 900 mg/m2 intravenously on Day 1 and Day 8. Additionally on Day 8, patients will have Docetaxel 100 mg/m2 given intravenously. on a 21 day cycle. If disease progression occurs on this treatment, patients will have the option to receive treatment with Gemcitabine and Pazopanib (group 1). Gemcitabine and Docetaxel: Gemcitabine 900 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Docetaxel 100 mg/m2 by IV on day 8 of a 21 day cycle.
Rate of Participants With Grade 3 or Higher Toxicity	39 Participants	39 Participants

SECONDARY outcome

Timeframe: minimum of 18 months

Hazard ratio is defined as the rate of survival in the experimental group versus the standard of care group. A hazard ratio of greater than one or less than one means that survival was better in one of the groups.

Outcome measures

Outcome measures
Measure	Experimental n=45 Participants Patients in Group 1 will get Gemcitabine 1000 mg/m2 intravenously on Day 1 and Day 8 and Pazopanib 800mg by mouth daily on a 21 day cycle. Cycles will continue until disease progression or patient withdrawal. Gemcitabine and Pazopanib: Gemcitabine 1000 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Pazopanib 800 mg by oral tablet daily for a 21 day cycle.	Standard of Care n=45 Participants Patients in Group 2 will get Gemcitabine 900 mg/m2 intravenously on Day 1 and Day 8. Additionally on Day 8, patients will have Docetaxel 100 mg/m2 given intravenously. on a 21 day cycle. If disease progression occurs on this treatment, patients will have the option to receive treatment with Gemcitabine and Pazopanib (group 1). Gemcitabine and Docetaxel: Gemcitabine 900 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Docetaxel 100 mg/m2 by IV on day 8 of a 21 day cycle.
Hazard Ratio	1.2 hazard ratio Interval 0.7 to 2.0	NA hazard ratio Not applicable; outcome is expressed as a single ratio

SECONDARY outcome

Timeframe: Baseline, Cycle 2, Cycle 6 and End of Treatment

To estimate the quality of life of patient with metastatic an/or locally advanced recurrent STS using the Quality of Life Questionnaire (QLQ-C30). The QLQ-C30 is scored on a scale from 0-100 with "0" indicating "never" and "100" indicating "always" in regard the the participants' experience of fatigue, nausea/vomiting, pain, disponae, insomnia, appetite loss, constipation, diarrhea, financial concerns at 4 time points through the study.

Outcome measures

Outcome measures
Measure	Experimental n=45 Participants Patients in Group 1 will get Gemcitabine 1000 mg/m2 intravenously on Day 1 and Day 8 and Pazopanib 800mg by mouth daily on a 21 day cycle. Cycles will continue until disease progression or patient withdrawal. Gemcitabine and Pazopanib: Gemcitabine 1000 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Pazopanib 800 mg by oral tablet daily for a 21 day cycle.	Standard of Care n=45 Participants Patients in Group 2 will get Gemcitabine 900 mg/m2 intravenously on Day 1 and Day 8. Additionally on Day 8, patients will have Docetaxel 100 mg/m2 given intravenously. on a 21 day cycle. If disease progression occurs on this treatment, patients will have the option to receive treatment with Gemcitabine and Pazopanib (group 1). Gemcitabine and Docetaxel: Gemcitabine 900 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Docetaxel 100 mg/m2 by IV on day 8 of a 21 day cycle.
Average Score of Quality of Life Diarrhea at end of study	21.43 score on a scale Standard Deviation 22.62	15.28 score on a scale Standard Deviation 24.04
Average Score of Quality of Life Financial at cycle 2	26.67 score on a scale Standard Deviation 34.69	22.22 score on a scale Standard Deviation 27.22
Average Score of Quality of Life Fatigue at baseline	61.79 score on a scale Standard Deviation 27.89	67.12 score on a scale Standard Deviation 23.44
Average Score of Quality of Life Nausea/Vommiting at baseline	91.06 score on a scale Standard Deviation 14.48	90.99 score on a scale Standard Deviation 16.94
Average Score of Quality of Life Pain at baseline	61.38 score on a scale Standard Deviation 32.80	74.77 score on a scale Standard Deviation 25.65
Average Score of Quality of Life Dysponae at baseline	22.76 score on a scale Standard Deviation 32.86	21.62 score on a scale Standard Deviation 29.62
Average Score of Quality of Life Insomnia at baseline	45.53 score on a scale Standard Deviation 39.97	36.04 score on a scale Standard Deviation 30.81
Average Score of Quality of Life Constipation at baseline	14.63 score on a scale Standard Deviation 26.92	15.32 score on a scale Standard Deviation 23.03
Average Score of Quality of Life Diarrhea at baseline	4.88 score on a scale Standard Deviation 11.93	8.11 score on a scale Standard Deviation 16.49
Average Score of Quality of Life Fatigue at cycle 2	52.89 score on a scale Standard Deviation 23.85	55.09 score on a scale Standard Deviation 25.06
Average Score of Quality of Life Nausea/Vomitting at cycle 2	80.67 score on a scale Standard Deviation 17.13	93.75 score on a scale Standard Deviation 9.60
Average Score of Quality of Life Appetite loss at cycle 2	36.11 score on a scale Standard Deviation 32.48	26.39 score on a scale Standard Deviation 32.57
Average Score of Quality of Life Diarrhea at cycle 2	4.88 score on a scale Standard Deviation 11.93	8.11 score on a scale Standard Deviation 16.49
Average Score of Quality of Life Fatigue at cycle 6	64.44 score on a scale Standard Deviation 11.48	51.11 score on a scale Standard Deviation 30.63
Average Score of Quality of Life Nausea/vommiting at cycle 6	86.67 score on a scale Standard Deviation 7.03	8.05 score on a scale Standard Deviation 95.00
Average Score of Quality of Life Pain at cycle 6	80.00 score on a scale Standard Deviation 23.31	78.33 score on a scale Standard Deviation 30.48
Average Score of Quality of Life Dyspnoae at cycle 6	10.00 score on a scale Standard Deviation 16.10	43.33 score on a scale Standard Deviation 22.50
Average Score of Quality of Life Insomnia at cycle 6	23.33 score on a scale Standard Deviation 16.10	33.33 score on a scale Standard Deviation 27.22
Average Score of Quality of Life Appetite loss at cycle 6	26.67 score on a scale Standard Deviation 34.43	30.00 score on a scale Standard Deviation 24.60
Average Score of Quality of Life Constipation at cycle 6	13.33 score on a scale Standard Deviation 17.21	13.33 score on a scale Standard Deviation 23.31
Average Score of Quality of Life Fatigue at end of study	49.81 score on a scale Standard Deviation 22.74	49.77 score on a scale Standard Deviation 25.77
Average Score of Quality of Life Nausea/vomitting at end of study	75.86 score on a scale Standard Deviation 23.82	92.36 score on a scale Standard Deviation 12.02
Average Score of Quality of Life Pain at end of study	53.45 score on a scale Standard Deviation 32.85	72.92 score on a scale Standard Deviation 24.48
Average Score of Quality of Life Dysponae at end of study	31.03 score on a scale Standard Deviation 33.25	34.72 score on a scale Standard Deviation 28.62
Average Score of Quality of Life Insomnia at end of study	48.28 score on a scale Standard Deviation 36.28	37.50 score on a scale Standard Deviation 26.58
Average Score of Quality of Life Appetite loss at end of study	37.93 score on a scale Standard Deviation 33.00	23.61 score on a scale Standard Deviation 28.62
Average Score of Quality of Life Constipation at end of study	17.24 score on a scale Standard Deviation 24.59	29.17 score on a scale Standard Deviation 30.00
Average Score of Quality of Life Financial at end of study	39.60 score on a scale Standard Deviation 39.29	29.17 score on a scale Standard Deviation 33.06
Average Score of Quality of Life Appetite loss at baseline	22.76 score on a scale Standard Deviation 32.01	15.32 score on a scale Standard Deviation 26.75
Average Score of Quality of Life Financial at baseline	37.40 score on a scale Standard Deviation 40.96	32.43 score on a scale Standard Deviation 34.68
Average Score of Quality of Life Pain at cycle 2	66.00 score on a scale Standard Deviation 26.56	83.33 score on a scale Standard Deviation 20.85
Average Score of Quality of Life Dyspnoae at cycle 2	24.00 score on a scale Standard Deviation 24.57	26.39 score on a scale Standard Deviation 24.04
Average Score of Quality of Life Insomnia at cycle 2	42.67 score on a scale Standard Deviation 34.05	38.89 score on a scale Standard Deviation 28.94
Average Score of Quality of Life Constipation at cycle 2	13.33 score on a scale Standard Deviation 21.52	23.61 score on a scale Standard Deviation 25.02
Average Score of Quality of Life Diarrhea at cycle 6	36.67 score on a scale Standard Deviation 24.60	20.00 score on a scale Standard Deviation 23.31
Average Score of Quality of Life Financial at cycle 6	23.33 score on a scale Standard Deviation 31.62	20.00 score on a scale Standard Deviation 23.31

SECONDARY outcome

Timeframe: minimum of 18 months

Response rate is defined as follows: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study

Outcome measures

Outcome measures
Measure	Experimental n=43 Participants Patients in Group 1 will get Gemcitabine 1000 mg/m2 intravenously on Day 1 and Day 8 and Pazopanib 800mg by mouth daily on a 21 day cycle. Cycles will continue until disease progression or patient withdrawal. Gemcitabine and Pazopanib: Gemcitabine 1000 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Pazopanib 800 mg by oral tablet daily for a 21 day cycle.	Standard of Care n=45 Participants Patients in Group 2 will get Gemcitabine 900 mg/m2 intravenously on Day 1 and Day 8. Additionally on Day 8, patients will have Docetaxel 100 mg/m2 given intravenously. on a 21 day cycle. If disease progression occurs on this treatment, patients will have the option to receive treatment with Gemcitabine and Pazopanib (group 1). Gemcitabine and Docetaxel: Gemcitabine 900 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Docetaxel 100 mg/m2 by IV on day 8 of a 21 day cycle.
Response Rate Complete Response	0 Participants	0 Participants
Response Rate Partial Response	5 Participants	8 Participants
Response Rate Stable Disease	24 Participants	21 Participants
Response Rate Progressive Disease	14 Participants	16 Participants

Adverse Events

Experimental

Serious events: 28 serious events

Other events: 45 other events

Deaths: 32 deaths

Standard of Care

Serious events: 31 serious events

Other events: 45 other events

Deaths: 30 deaths

Serious adverse events

Other adverse events

Additional Information

Cameron Coggins

MUSC

Phone: 843-792-4743

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Experimental n=45 participants at risk Patients in Group 1 will get Gemcitabine 1000 mg/m2 intravenously on Day 1 and Day 8 and Pazopanib 800mg by mouth daily on a 21 day cycle. Cycles will continue until disease progression or patient withdrawal. Gemcitabine and Pazopanib: Gemcitabine 1000 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Pazopanib 800 mg by oral tablet daily for a 21 day cycle.	Standard of Care n=45 participants at risk Patients in Group 2 will get Gemcitabine 900 mg/m2 intravenously on Day 1 and Day 8. Additionally on Day 8, patients will have Docetaxel 100 mg/m2 given intravenously. on a 21 day cycle. If disease progression occurs on this treatment, patients will have the option to receive treatment with Gemcitabine and Pazopanib (group 1). Gemcitabine and Docetaxel: Gemcitabine 900 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Docetaxel 100 mg/m2 by IV on day 8 of a 21 day cycle.
General disorders Pain	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
General disorders Edema Limbs	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
General disorders Edema Trunk	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
General disorders Fatigue	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Infections and infestations Bacterial Infection	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Infections and infestations Lung Infection	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Infections and infestations Sepsis	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Injury, poisoning and procedural complications Spinal Fracture	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Injury, poisoning and procedural complications Vascular Access Complication	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Injury, poisoning and procedural complications Fracture	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Investigations Platelet Count Decrease	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Investigations Alanine Aminotransferase Increased	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bleeding from Tumor	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Nervous system disorders Ischemia Cerebrovascular	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Metabolism and nutrition disorders Dehydration	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Musculoskeletal and connective tissue disorders Bone Pain/Right leg	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Vascular disorders Hypotension	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Respiratory, thoracic and mediastinal disorders Acute Left Lung Pneumonia/Infection	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Vascular disorders Thromboembolic Event	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Infections and infestations Other Infection	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
General disorders Fever	6.7% 3/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	6.7% 3/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Gastrointestinal disorders Nausea	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Gastrointestinal disorders Pancreatitis	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Gastrointestinal disorders Vomiting	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Gastrointestinal disorders Ascites	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Cardiac disorders Asystole	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Cardiac disorders Atrial Fibrilation	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Cardiac disorders Heart Failure	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Cardiac disorders Pericardial Tamponade	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Cardiac disorders Supraventricular Tachycardia	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Blood and lymphatic system disorders Anemia	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	2.2% 1/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.

Measure	Experimental n=45 participants at risk Patients in Group 1 will get Gemcitabine 1000 mg/m2 intravenously on Day 1 and Day 8 and Pazopanib 800mg by mouth daily on a 21 day cycle. Cycles will continue until disease progression or patient withdrawal. Gemcitabine and Pazopanib: Gemcitabine 1000 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Pazopanib 800 mg by oral tablet daily for a 21 day cycle.	Standard of Care n=45 participants at risk Patients in Group 2 will get Gemcitabine 900 mg/m2 intravenously on Day 1 and Day 8. Additionally on Day 8, patients will have Docetaxel 100 mg/m2 given intravenously. on a 21 day cycle. If disease progression occurs on this treatment, patients will have the option to receive treatment with Gemcitabine and Pazopanib (group 1). Gemcitabine and Docetaxel: Gemcitabine 900 mg/m2 by IV on day 1 and day 8 of a 21 day cycle. Docetaxel 100 mg/m2 by IV on day 8 of a 21 day cycle.
General disorders Fatigue	75.6% 34/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	62.2% 28/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Investigations Platelet Count Decreased	75.6% 34/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	73.3% 33/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Gastrointestinal disorders Nausea	68.9% 31/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	40.0% 18/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Blood and lymphatic system disorders Anemia	60.0% 27/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	71.1% 32/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Gastrointestinal disorders Constipation	28.9% 13/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	42.2% 19/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Investigations Neutrophil Count Decreased	57.8% 26/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	24.4% 11/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
General disorders Edema Limbs	15.6% 7/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	35.6% 16/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Gastrointestinal disorders Vomiting	55.6% 25/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
General disorders Pain	35.6% 16/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	35.6% 16/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Gastrointestinal disorders Diarrhea	48.9% 22/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	31.1% 14/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Investigations Alanine Aminotransferase Increased	44.4% 20/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	26.7% 12/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Respiratory, thoracic and mediastinal disorders Dyspnea	22.2% 10/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	31.1% 14/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Metabolism and nutrition disorders Anorexia	35.6% 16/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	28.9% 13/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Metabolism and nutrition disorders Hyperglycemia	26.7% 12/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	28.9% 13/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Investigations White Blood Cell Decreased	42.2% 19/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	28.9% 13/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Investigations Aspartate Aminotransferase Increased	44.4% 20/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	26.7% 12/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Respiratory, thoracic and mediastinal disorders Cough	20.0% 9/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	26.7% 12/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Nervous system disorders Dysgeusia	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	26.7% 12/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Musculoskeletal and connective tissue disorders Myalgia	6.7% 3/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	26.7% 12/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
General disorders Fever	17.8% 8/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	24.4% 11/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Metabolism and nutrition disorders Hypokalemia	15.6% 7/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	24.4% 11/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Gastrointestinal disorders Mucositis Oral	15.6% 7/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	24.4% 11/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Nervous system disorders Peripheral Sensory Neuropathy	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	24.4% 11/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Investigations Alkaline Phosphatase Increased	28.9% 13/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	22.2% 10/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Nervous system disorders Headache	33.3% 15/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	22.2% 10/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Investigations Lymphocyte Count Decreased	20.0% 9/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	22.2% 10/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Metabolism and nutrition disorders Hypoalbuminemia	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	20.0% 9/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Metabolism and nutrition disorders Hyponatremia	13.3% 6/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	20.0% 9/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Skin and subcutaneous tissue disorders Alopecia	6.7% 3/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	17.8% 8/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Respiratory, thoracic and mediastinal disorders Epistaxis	20.0% 9/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	17.8% 8/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Musculoskeletal and connective tissue disorders Bone Pain	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	15.6% 7/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Metabolism and nutrition disorders Hypocalcemia	6.7% 3/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	15.6% 7/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Psychiatric disorders Insomnia	20.0% 9/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	15.6% 7/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Nervous system disorders Dizziness	15.6% 7/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	13.3% 6/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Skin and subcutaneous tissue disorders Nail Discoloration	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	13.3% 6/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Gastrointestinal disorders Abdominal Pain	15.6% 7/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Investigations Creatinine Increased	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Psychiatric disorders Depression	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Musculoskeletal and connective tissue disorders Generalized Muscle Weakness	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Metabolism and nutrition disorders Hypernatremia	6.7% 3/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Skin and subcutaneous tissue disorders Palmarplantar Erythrodysesthesia Syndrome	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Vascular disorders Hypertension	35.6% 16/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	6.7% 3/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Respiratory, thoracic and mediastinal disorders Hoarseness	15.6% 7/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	0.00% 0/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Investigations Blood Bilirubin Increased	13.3% 6/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
General disorders Noncardiac Chest Pain	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	4.4% 2/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.
Musculoskeletal and connective tissue disorders Pain In Extremity	11.1% 5/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.	6.7% 3/45 • study enrollment to 30 days from last treatment; inclusive of crossover treatment AE data was collected from subjects at every clinic visit and day 1 of every cycle.