Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma (RCC)

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01392183
• Collaborator: Novartis (Industry)
• Enrollment: 69
• Location: 1
• Arms: 2
• Actual Duration (Months): 82.5
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to compare pazopanib to temsirolimus in the treatment of advanced clear-cell renal cell carcinoma. The safety of each drug will also be studied.

Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells.

Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells to die.

This is an investigational study. Pazopanib and temsirolimus are both FDA approved and commercially available for the treatment of kidney cancer. It is investigational to compare the 2 drugs.

Up to 90 patients will be enrolled in this study. All will be enrolled at MD Anderson.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer	Drug: Pazopanib; Drug: Temsirolimus; Behavioral: Quality of Life Assessment; Drug: Benadryl	Phase 2

Detailed Description

Study Groups and Study Drug Administration:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. You will have an equal chance of being assigned to either group.

• If you are assigned to Group 1, you will take pazopanib by mouth 1 time every day at about the same time each day on an empty stomach (at least 1 hour before or 2 hours after a meal).

• If you are assigned to Group 2, you will receive temsirolimus by vein 1 time every week over 30-60 minutes. About 30 minutes before you receive each dose of temsirolimus, you will receive Benadryl (diphenhydramine) by vein over 1-2 minutes to help lower the risk of side effects.

If you are assigned to Group 1, do not crush tablets and do not repeat missed doses if it is less than 12 hours until your next scheduled dose. You will be given a pill diary to record when you take each dose. You will return the diary to the study doctor at each study visit.

If you have any side effects, you should tell the study doctor right away. If the study doctor thinks it is in your best interest, your dose may be lowered.

If the disease gets worse while you are on study, you will have the option to change to the study group you were not originally assigned to and take the other study drug. The study drug dosing and study visit schedule will be the same, and the study doctor will discuss any important details with you at the time you change study groups.

Study Visits:

Every 4 weeks on this study is called a study cycle.

Every week during Cycle 1 (Group 1 only), your blood pressure will be checked (either at home, at the clinic, or by your local doctor). If you are checking your own blood pressure at home, you will need to write down your blood pressure in a blood pressure diary each time you check it and bring the diary with you to each clinic visit.

Every 2 weeks for the first 2 cycles (Group 1 only) , blood (about 3 tablespoons) will be drawn for routine tests.

Every week (Group 2 only), blood (about 1 tablespoon) will be drawn for routine tests.

Every cycle (Group 2 only) OR Every other cycle (Group 1 only):

• You will have a physical exam, including measurement of your weight and vital signs.

• You will be asked about any drugs or treatments you may be receiving.

• You will be asked about any side effects you may have had.

• Blood (about 3 tablespoons) will be collected for routine tests.

On Day 1 of Cycle 2, Day 1 of Cycle 4, and every 4 cycles after that (Group 1 only), you will have an ECG to check your heart function.

If you are in Group 2 only, on Day 1 of Cycles 2, 3, and every other cycle after that (Cycles 5, 7, 9, and so on), blood (about 3 tablespoons) will be drawn for routine tests. You will be asked to fast (eat nothing and drink only water) for at least 8 hours before those blood draws.

Every 2 cycles:

• You will have the same imaging scans that you had at screening. After 1 year on treatment, these imaging scans may only be done every 3 cycles (Cycles 5, 8, 11, and so on).

• You will fill out the quality-of-life questionnaires.

• Blood (about 2 teaspoons) will be drawn for tests to check your thyroid function (Group 1 only).

• Urine will be collected for routine tests.

Every 4 cycles, you will have an ECG (Group 2 only).

Every 6 cycles, you will have an ECHO or MUGA scan to check your heart function.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take a study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

End-of-Treatment Follow- up:

About 30 days after you stop treatment, during a clinic visit or by phone, you will be asked about any drugs or treatments you may be receiving and any side effects you may have had.

Long-Term Follow-up:

After you stop taking the study drug, the study staff will check up on you to ask how you are doing about every 3 months from then on. The study staff will collect the information they need either from your medical records or by calling you. If you are contacted by phone, the call should only last about 5 minutes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase 2 Trial of Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma
• Actual Study Start Date: Oct 24, 2012
• Actual Primary Completion Date: Sep 8, 2019
• Actual Study Completion Date: Sep 8, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pazopanib Pazopanib 800 mg by mouth daily. Quality of Life Assessment - Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.	Drug: Pazopanib; 800 mg by mouth daily in 4 week study cycle.; Other Names: GW786034 ; Behavioral: Quality of Life Assessment; Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.; Other Names: Questionnaires Surveys
Experimental: Temsirolimus Temsirolimus 25 mg by vein infused over 30-60 minutes weekly. Benadryl 25 to 50 mg by vein approximately 30 minutes before the start of each dose of temsirolimus. Quality of Life Assessment - Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.	Drug: Temsirolimus; 25 mg by vein infused over 30-60 minutes every week in 4 week study cycle.; Other Names: CCI-779 Torisel ; Behavioral: Quality of Life Assessment; Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.; Other Names: Questionnaires Surveys ; Drug: Benadryl; 25 to 50 mg by vein approximately 30 minutes before the start of each dose of temsirolimus.; Other Names: Diphenhydramine

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [Measured form start of treatment up to 3 years]

   PFS is measured from the initiation of treatment to the time of first disease progression or death due to any reason during the first drug administration in each arm. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% or more increase in the sum of the longest diameters of target lesions, or a measurable increase in a non-target lesion or the appearance of new lesions. The PFS median of first drug pazopanib (treatment group) was compared to the PFS median of first drug temsirolimus (control group) in an adjusted Hazard ratio. The hazard ratio compares events from a treatment group to a control group. If the hazard ratio is greater than 1the treatment group performed better. If the hazard ratio is less than 1 the control group performed better. If the hazard ratio is equal to 1, then the groups performed equally.

Secondary Outcome Measures

1. Overall Survival (OS) [From the start of treatment up to 6 years or death, whichever came first]

   Overall survival is calculated from day of therapy initiation of the first administrated drug to the date of death. Kaplan-Meier estimator used to estimate the OS for each group of participants. The Overall Survival median of first drug pazopanib (treatment group) was compared to the Overall Survival median of first drug temsirolimus (control group) in an adjusted Hazard ratio. The hazard ratio compares events from a treatment group to a control group. If the hazard ratio is greater than 1the treatment group performed better. If the hazard ratio is less than 1 the control group performed better. If the hazard ratio is equal to 1, then the groups performed equally.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Pathologic confirmation of metastatic or locally advanced RCC with a major clear cell component.

2. Measurable disease by RECIST criteria.

3. Age >/= 18 years

4. ECOG performance status 0-2 or Karnofsky Performance Status >/= 60%

5. Meets criteria for poor-risk defined as 3 or more of the following: ECOG performance status 2, anemia (hemoglobin lower than reference range), elevated serum LDH > 1.5x upper limit of normal (ULN), hypercalcemia (corrected serum calcium level > upper limit of normal), time from initial RCC diagnosis to registration on this trial < 1 year, and > 1 metastatic organ sites.

6. Adequate organ and marrow function within 14 days of registration as defined below: a) Absolute neutrophil count >/=1,500/µL b) Platelets >/=100,000/µL c) Hgb >/= 9.0 g/dL (transfusion allowed) d) Renal: serum creatinine </= 1.5 x ULN or calculated CrCl >/= 40 cc/min and random urine protein:creatinine ratio (UPC) < 1 or 24-hr urine protein < 1g e) Liver: total bilirubin </= 1.5 mg/dl; AST (SGOT) and ALT (SGPT) </= 2.5 x ULN for subjects without evidence of liver metastases, </= 5 x ULN for subjects with documented liver metastases f) INR </= 1.2 x ULN; PTT </= 1.5 x ULN. Therapeutic anticoagulation with warfarin is allowed if target INR </= 3 on a stable dose of warfarin or on a stable dose of LMW heparin for > 2 weeks (14 days) at time of randomization.

7. Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test within 14 days of study registration. Pregnancy test must be repeated if performed > 14 days before starting study drug.

Exclusion Criteria:

1. Prior malignancy, except for non-melanoma skin cancer, in situ carcinoma of any site, or other cancers for which the patient has been adequately treated and disease free for 2 years

2. Prior targeted therapy (anti-VEGF agents or mTOR inhibitors) including adjuvant therapy, and prior chemotherapy for mRCC. However, prior immunotherapy (cytokines or vaccines) is allowed.

3. Any experimental drug while on this study; however, concomitant bone targeted therapy (bisphosphonates or the anti-RANK ligand denosumab) is allowed.

4. Uncontrolled brain metastases and infections. Patients with brain metastases treated with Gamma Knife (GK) or whole brain radiation within 24 hours of registration.

5. History of stroke within 6 months of registration

6. Clinically significant cardiovascular disease, defined as myocardial infarction (or unstable angina) within 6 months of registration, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac dysrhythmia refractory to medical management. However, treated and controlled or stable/not clinically significant cardiovascular disease is allowed per evaluation by cardiologist.

7. Uncontrolled hypertension (home blood pressure readings are permitted) or prior history of hypertensive crisis or hypertensive encephalopathy; however, treatment of hypertension with medications is permitted.

8. History of uncontrolled hemoptysis (>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1

9. Significant vascular disease including aortic aneurysm, aortic dissection.

10. Symptomatic peripheral vascular disease

11. Pregnancy

12. HIV-positive patients receiving combination anti-retroviral therapy

13. Coagulopathy or bleeding diathesis

14. Concomitant treatment with rifampin, St. John's wort, or the cytochrome p450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital)

15. Major surgery within 28 days prior to registration

16. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device within 7 days prior to starting drug

17. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study registration

18. Serious non-healing wound

19. Baseline QTcB >/= 470 msec.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Novartis

Investigators

• Principal Investigator: Amado Zurita, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 23, 2017

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01392183
• Other Study ID Numbers: 2011-0358; NCI-2011-01277
• First Posted: Jul 12, 2011
• Last Update Posted: Sep 20, 2021
• Last Verified: Aug 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Kidney cancer; Renal Cell Carcinoma; Poor-Risk Clear-Cell Renal Cell Carcinoma; RCC; Metastatic; Locally advanced; Complete response; CR; Partial Response; PR; Overall survival; OS; Time to progression; TTP; Pazopanib; GW786034; Temsirolimus; CCI-779; Torisel; Benadryl; Diphenhydramine; TemPa
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms; Diphenhydramine; Sirolimus

Study Results

Participant Flow

Recruitment Details	Recruitment Period: October 2012 to September 2017

Arm/Group Title	Temsirolimus (Control Group)	Pazopanib (Treatment Group)
Arm/Group Description	Temsirolimus 25 mg intravenously weekly. Upon progression patient crosses over over to pazopanib 800 mg orally daily. Treatments stop for progression, toxicity, withdrawal, or death.	Pazopanib 800 mg orally daily. Upon progression patient crosses over to temsirolimus 25 mg intravenously weekly. Treatments stop for progression, toxicity, withdrawal, or death.
Period Title: First Drug Administration
STARTED	35	34
Eligible to Cross Over to 2nd Drug	29	31
COMPLETED	21	15
NOT COMPLETED	14	19
Period Title: First Drug Administration
STARTED	21	15
Treatment Ended: Progression	18	11
Treatment Ended: Adverse Events	1	2
Treatment Ended: Participant Withdrew	2	1
Treatment Ended: Death	0	1
COMPLETED	21	15
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Temsirolimus (Control Group)	Pazopanib (Treatment Group)	Total
Arm/Group Description	Temsirolimus 25 mg intravenously weekly. Upon progression patient crosses over to pazopanib 800 mg orally daily. Treatments stop for progression, toxicity, withdrawal, or death.	Pazopanib 800 mg orally daily. Upon progression patient crosses over to temsirolimus 25 mg intravenously weekly. Treatments stop for progression, toxicity, withdrawal, or death.	Total of all reporting groups
Overall Participants	35	34	69
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61	61	61
Sex: Female, Male (Count of Participants)
Female	11 31.4%	6 17.6%	17 24.6%
Male	24 68.6%	28 82.4%	52 75.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 14.3%	3 8.8%	8 11.6%
Not Hispanic or Latino	11 31.4%	13 38.2%	24 34.8%
Unknown or Not Reported	19 54.3%	18 52.9%	37 53.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.9%	0 0%	1 1.4%
Asian	0 0%	4 11.8%	4 5.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 5.7%	1 2.9%	3 4.3%
White	27 77.1%	26 76.5%	53 76.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	5 14.3%	3 8.8%	8 11.6%
Region of Enrollment (participants) [Number]
United States	35 100%	34 100%	69 100%
Karnofsky Performance Status (KPS) Score (Count of Participants)
100%	1 2.9%	1 2.9%	2 2.9%
90%	12 34.3%	10 29.4%	22 31.9%
80%	2 5.7%	2 5.9%	4 5.8%
70%	20 57.1%	21 61.8%	41 59.4%
Eastern Cooperative Oncology Group (ECOG) Performance Score (Count of Participants)
0	1 2.9%	1 2.9%	2 2.9%
1	14 40%	12 35.3%	26 37.7%
2	20 57.1%	21 61.8%	41 59.4%
Poor -Risk With Disease Eligibility Score. (Count of Participants)
3 Factors	12 34.3%	12 35.3%	24 34.8%
4 Factors	18 51.4%	19 55.9%	37 53.6%
5 Factors	5 14.3%	3 8.8%	8 11.6%
International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Risk Score (Count of Participants)
Favorable risk	0 0%	0 0%	0 0%
Intermediate risk	11 31.4%	8 23.5%	19 27.5%
Poor Risk	24 68.6%	26 76.5%	50 72.5%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	PFS is measured from the initiation of treatment to the time of first disease progression or death due to any reason during the first drug administration in each arm. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% or more increase in the sum of the longest diameters of target lesions, or a measurable increase in a non-target lesion or the appearance of new lesions. The PFS median of first drug pazopanib (treatment group) was compared to the PFS median of first drug temsirolimus (control group) in an adjusted Hazard ratio. The hazard ratio compares events from a treatment group to a control group. If the hazard ratio is greater than 1the treatment group performed better. If the hazard ratio is less than 1 the control group performed better. If the hazard ratio is equal to 1, then the groups performed equally.
Time Frame	Measured form start of treatment up to 3 years

Outcome Measure Data

Analysis Population Description

The ratio is comparing both arms to each other, therefore the data would be identical.

Arm/Group Title	Temsirolimus (Control Group)	Pazopanib (Treatment Group)
Arm/Group Description	Temsirolimus 25 mg intravenously weekly. Upon progression patient crosses over to pazopanib 800 mg orally daily. Treatments stop for progression, toxicity, withdrawal, or death.	Pazopanib 800 mg orally daily. Upon progression patient crosses over to temsirolimus 25 mg intravenously weekly. Treatments stop for progression, toxicity, withdrawal, or death
Measure Participants	35	34
Median (Full Range) [months]	2.7	5.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Temsirolimus (Control Group), Pazopanib (Treatment Group)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 0.84 to 2.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted Hazard Ratio comparing Median PFS of pazopanib (treatment group) to Temsirolimus (control group) as first line of treatment. HR >1 treatment group performed better, < 1 the control group performed better =1 groups performed equally.

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is calculated from day of therapy initiation of the first administrated drug to the date of death. Kaplan-Meier estimator used to estimate the OS for each group of participants. The Overall Survival median of first drug pazopanib (treatment group) was compared to the Overall Survival median of first drug temsirolimus (control group) in an adjusted Hazard ratio. The hazard ratio compares events from a treatment group to a control group. If the hazard ratio is greater than 1the treatment group performed better. If the hazard ratio is less than 1 the control group performed better. If the hazard ratio is equal to 1, then the groups performed equally.
Time Frame	From the start of treatment up to 6 years or death, whichever came first

Outcome Measure Data

Analysis Population Description

The ratio is comparing both arms to each other, therefore the data would be identical.

Arm/Group Title	Temsirolimus (Control Group)	Pazopanib (Treatment Group)
Arm/Group Description	Temsirolimus 25 mg intravenously weekly. Upon progression patient crosses over to pazopanib 800 mg orally daily. Treatments stop for progression, toxicity, withdrawal, or death	Pazopanib 800 mg orally daily. Pazopanib 800 mg orally daily. Upon progression patient crosses over to temsirolimus 25 mg intravenously weekly. Treatments stop for progression, toxicity, withdrawal, or death
Measure Participants	35	34
Median (Full Range) [months]	7.1	11.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Temsirolimus (Control Group), Pazopanib (Treatment Group)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.7 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted HR comparing Median OS of pazopanib (treatment group) to Temsirolimus (control group) as first line of treatment. HR >1 treatment group performed better, < 1 the control group performed better =1 groups performed equally.

Adverse Events

Time Frame	Baseline to study completion or date of death from any cause, whichever came first, assessed up to 5 years.
Adverse Event Reporting Description	The total at Risk are participants who received the intervention as their first drug or second drug. All participants did not received both drugs.
Arm/Group Title	Temsirolimus (Control Group)		Pazopanib (Treatment Group)
Arm/Group Description	Temsirolimus 25 mg intravenously weekly. Upon progression patient crosses over to pazopanib 800 mg orally daily. Treatments stop for progression, toxicity, withdrawal, or death.		Pazopanib 800 mg orally daily. Upon progression patient crosses over to temsirolimus 25 mg intravenously weekly. Treatments stop for progression, toxicity, withdrawal, or death.
All Cause Mortality
	Temsirolimus (Control Group)		Pazopanib (Treatment Group)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/50 (64%)		31/55 (56.4%)
Serious Adverse Events
	Temsirolimus (Control Group)		Pazopanib (Treatment Group)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/50 (30%)		10/55 (18.2%)
Blood and lymphatic system disorders
Platelet Count Decreased	0/50 (0%)	0	1/55 (1.8%)	1
Edema	3/50 (6%)	3	0/55 (0%)	0
Thrombotic thrombocytopenic purpura	0/50 (0%)	0	1/55 (1.8%)	1
Cardiac disorders
Chest pain-cardic	1/50 (2%)	1	0/55 (0%)	0
Endocrine disorders
Hyperglycemia	1/50 (2%)	1	0/55 (0%)	0
Gastrointestinal disorders
Nausea	2/50 (4%)	2	1/55 (1.8%)	1
Enterocolitis	1/50 (2%)	1	0/55 (0%)	0
Vomiting	1/50 (2%)	1	0/55 (0%)	0
General disorders
Fatigue	1/50 (2%)	1	0/55 (0%)	0
Immune system disorders
Infusion Related Reaction	1/50 (2%)	1	0/55 (0%)	0
Metabolism and nutrition disorders
Hypophosphatemia	0/50 (0%)	0	1/55 (1.8%)	1
Nervous system disorders
Back Pain	0/50 (0%)	0	1/55 (1.8%)	1
Pain	1/50 (2%)	1	0/55 (0%)	0
Renal and urinary disorders
Acute Kidney Injury	1/50 (2%)	1	2/55 (3.6%)	2
Urinary Tract Infection	0/50 (0%)	0	1/55 (1.8%)	1
Creatinine Increased	1/50 (2%)	1	1/55 (1.8%)	1
Respiratory, thoracic and mediastinal disorders
Non-cardiac chest pain	1/50 (2%)	1	0/55 (0%)	0
Dyspnea	3/50 (6%)	3	0/55 (0%)	0
Pneumonitis	1/50 (2%)	1	0/55 (0%)	0
Pleural Effusion	1/50 (2%)	1	0/55 (0%)	0
Pneumonia	2/50 (4%)	2	0/55 (0%)	0
Skin and subcutaneous tissue disorders
Mucositis oral	0/50 (0%)	0	1/55 (1.8%)	1
Skin breakdown	0/50 (0%)	0	1/55 (1.8%)	1
Other (Not Including Serious) Adverse Events
	Temsirolimus (Control Group)		Pazopanib (Treatment Group)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/50 (70%)		33/55 (60%)
Blood and lymphatic system disorders
Anemia	31/50 (62%)	112	8/55 (14.5%)	18
lymphocyte Count Decreased	8/50 (16%)	21	8/55 (14.5%)	20
Neutrophil count decreased	1/50 (2%)	3	3/55 (5.5%)	4
Platelet count decreased	9/50 (18%)	10	16/55 (29.1%)	37
White blood cell decreased	7/50 (14%)	12	10/55 (18.2%)	24
Endocrine disorders
Hypothyroidism	0/50 (0%)	0	26/55 (47.3%)	29
Eye disorders
Watering eyes	2/50 (4%)	2	3/55 (5.5%)	5
Gastrointestinal disorders
Abdominal Pain	4/50 (8%)	5	8/55 (14.5%)	12
Anorexia	9/50 (18%)	15	18/55 (32.7%)	25
Constipation	7/50 (14%)	8	14/55 (25.5%)	22
Diarrhea	7/50 (14%)	7	33/55 (60%)	85
Dry Mouth	1/50 (2%)	1	3/55 (5.5%)	3
Mucositis oral	27/50 (54%)	48	12/55 (21.8%)	29
Nausea	13/50 (26%)	15	32/55 (58.2%)	79
Vomiting	5/50 (10%)	7	23/55 (41.8%)	44
Dysgeusia	10/50 (20%)	10	19/55 (34.5%)	26
General disorders
Edema	18/50 (36%)	45	6/55 (10.9%)	12
Fatigue	5/50 (10%)	9	25/55 (45.5%)	65
Pain	4/50 (8%)	6	14/55 (25.5%)	21
Weight loss	4/50 (8%)	4	16/55 (29.1%)	21
Hepatobiliary disorders
ALT Increased	3/50 (6%)		19/55 (34.5%)	47
Alk Phos Increased	15/50 (30%)	27	17/55 (30.9%)	35
AST increased	9/50 (18%)	12	19/55 (34.5%)	53
GGT increased	0/50 (0%)	0	5/55 (9.1%)	14
Bilirubin increased	0/50 (0%)	0	6/55 (10.9%)	11
Investigations
Hypoalbuminemia	4/50 (8%)	5	11/55 (20%)	18
Metabolism and nutrition disorders
Hypoalbuminemia	8/50 (16%)	10	9/55 (16.4%)	17
Chholesterol high	4/50 (8%)	31	1/55 (1.8%)	1
Hyperglycemia	35/50 (70%)	127	22/55 (40%)	38
Hypernatremia	2/50 (4%)	5	11/55 (20%)	12
Hypertriglyeridemia	32/50 (64%)	49	3/55 (5.5%)	3
Hypokalemia	8/50 (16%)	12	2/55 (3.6%)	2
Hypomagnesemia	2/50 (4%)	5	6/55 (10.9%)	10
Hyponatremia	4/50 (8%)	8	9/55 (16.4%)	9
Hypophosphatemia	7/50 (14%)	12	3/55 (5.5%)	4
Hyperkalemia	0/50 (0%)	0	9/55 (16.4%)	12
Hypercalcemia	0/50 (0%)	0	3/55 (5.5%)	8
Musculoskeletal and connective tissue disorders
Chest Wall Pain	2/50 (4%)	3	4/55 (7.3%)	6
Generalized Muscle Weakness	0/50 (0%)	0	4/55 (7.3%)	5
Nervous system disorders
Headache	3/50 (6%)	4	3/55 (5.5%)	5
Neuropahty	1/50 (2%)	1	3/55 (5.5%)	3
Parasthesia	4/50 (8%)	5	5/55 (9.1%)	9
Renal and urinary disorders
Creatinine Increased	20/50 (40%)	34	15/55 (27.3%)	26
Hemoglobinuria	3/50 (6%)	3	0/55 (0%)	0
Proteinuria	11/50 (22%)	14	19/55 (34.5%)	36
Respiratory, thoracic and mediastinal disorders
Cough	5/50 (10%)	6	1/55 (1.8%)	1
Dyspnea	9/50 (18%)	13	8/55 (14.5%)	11
Epistaxis	2/50 (4%)	2	4/55 (7.3%)	5
Pneumonitis	3/50 (6%)	3	0/55 (0%)	0
Hoarse	0/50 (0%)	0	5/55 (9.1%)	10
Skin and subcutaneous tissue disorders
Alopecia	2/50 (4%)	2	5/55 (9.1%)	8
Dry Skin	5/50 (10%)	6	2/55 (3.6%)	2
Palmar-plantar erythrodeysesthesia	1/50 (2%)	2	6/55 (10.9%)	10
Rash	17/50 (34%)	49	22/55 (40%)	65
Skin hypopigmentation	1/50 (2%)	1	20/55 (36.4%)	38
Vascular disorders
Hypertension	5/50 (10%)	13	26/55 (47.3%)	53

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.