Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma

Study VEG108844, A Study of Pazopanib Versus Sunitinib in the Treatment of Subjects With Locally Advanced and/or Metastatic Renal Cell Carcinoma

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00720941

Acronym

COMPARZ

Enrollment

1110

Registered

2008-07-23

Start date

2008-08-14

Completion date

2021-03-24

Last updated

2025-03-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Carcinoma, Renal Cell

Keywords

SUTENT, Locally advanced and/or metastatic renal cell carcinoma, Pazopanib, Sunitinib, GW786034, Renal cell carcinoma

Brief summary

This was a randomized, open-label, parallel group Phase III non inferiority study to evaluate the efficacy and safety of pazopanib compared with sunitinib in subjects with advanced renal cell carcinoma (RCC) who had not received prior systemic therapy for advanced or metastatic RCC.

Detailed description

Approximately 876 eligible subjects (approximately 438 per treatment arm) were planned to be enrolled over the course of the study. However, due to higher than expected withdrawal rates and discordance rates between independent review committee (IRC) and investigator assessments of progression, the protocol was amended (Protocol Amendment 4) to increase the number of subjects to approximately 1100 total by including all subjects enrolled in CPZP034A2301 (hereafter referred as Study A2301) and CPZP034A2201 (a sub study of CPZP034A2301, hereafter referred as Study A2201 with NCT01147822). The subjects were centrally randomized in 1:1 ratio to receive either 800mg pazopanib to be administered once daily orally continuous dosing or 50mg sunitinib to be administered in 6-week cycles: 50mg orally daily for 4 weeks followed by 2 weeks off treatment. Subjects were permitted to receive supportive care throughout the study including transfusion of blood and blood products, treatment with antibiotics, anti-emetics, anti-diarrheal agents, analgesics, erythropoietin, or bisphosphonates, when appropriate. The study treatment continued until subjects experience disease progression, unacceptable toxicity, withdraw consent, or death.

Interventions

DRUGPazopanib

800 mg administered once daily orally continuous dosing

DRUGSunitinib

50 mg sunitinib to be administered in 6-week cycles: 50mg orally daily for 4 weeks followed by 2 weeks off treatment

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Written informed consent * Diagnosis of renal cell carcinoma with clear-cell component histology. * Received no prior systemic therapy (interleukin-2, interferon-alpha, chemotherapy, bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or metastatic RCC * Locally advanced or metastatic renal cell carcinoma * Measurable disease by CT or MRI * Karnofsky performance scale status of \>=70 * Age \>=18 years * A female is eligible to enter and participate in this study if she is of: non-childbearing or agrees to use adequate contraception. * Adequate organ system function * Total serum calcium concentration \<12.0mg/dL * Left ventricular ejection fraction \>= lower limit of institutional normal.

Exclusion criteria

* Pregnant or lactating female (unless agrees to refrain from nursing throughout the treatment period and for 14 days following the last dose of study) * History of another malignancy (unless have been disease-free for 3 years) * History or clinical evidence of central nervous system (CNS) metastases (unless have previously-treated CNS metastases and meet all 3 of the following criteria are: are asymptomatic, have had no evidence of active CNS metastases for \>=6 months prior to enrolment, and have no requirement for steroids or enzyme-inducing anticonvulsants) * Clinically significant gastrointestinal abnormalities including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, known intraluminal metastatic lesion/s with suspected bleeding, Inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment. * Presence of uncontrolled infection. * Prolongation of corrected QT interval (QTc) \> 480 milliseconds * History of any one or more of the following cardiovascular conditions within the past 12 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association * History of cerebrovascular accident including transient ischemic attack within the past 12 months * History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months (unless had recent DVT and have been treated with therapeutic anti-coagulating agents for at least 6 weeks) * Poorly controlled hypertension (defined as systolic blood pressure of \>=150mmHg or diastolic blood pressure of \>=90mmHg). Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry * Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer. * Evidence of active bleeding or bleeding susceptibility * Spitting/coughing up blood within 6 weeks of first dose of study drug * Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels * Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study. * Use any prohibited medications within 14 days of the first dose of study medication. * Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug. * Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors (eg. bevacizumab, sunitinib, sorafenib, etc), or are mTOR inhibitors (eg. temsirolimus, everolimus, etc). * Is now undergoing and/or has undergone in the 14 days immediately prior to first dose of study drug, any cancer therapy (surgery, tumor embolization, chemotherapy, radiation therapy, immunotherapy, biological therapy, or hormonal therapy) * Any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 and/or that is progressing in severity. * Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or sunitinib.

Design outcomes

Primary

Measure	Time frame	Description
Progression-free Survival (PFS)	From randomization until the earliest date of disease progression or date of death from any cause, assessed up to approximately 39 months	PFS was defined as the interval between the date of randomization and the earliest date of progressive disease (PD), as defined by the Independent Review Committee (IRC), or death due to any cause. The IRC defined PD per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1. Per RECIST, PD is defined as a \>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of \>=1 new lesion.

Secondary

Measure	Time frame	Description
Overall Survival	From randomization until date of death from any cause, assessed up to approximately 62 months	Overall survival was defined as the time from randomization until death due to any cause.
Number of Participants With Adverse Events	From study treatment start date till 28 days safety follow-up, assessed up to approximately 152 months	The distribution of adverse events was done via the analysis of frequencies for Adverse Event (AEs) and Serious Adverse Event (SAEs), through the monitoring of relevant clinical and laboratory safety parameters.
Overall Response Rate (ORR) as Assessed by Independent Review	From randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 39 months	The number of participants with evidence of Complete Response (CR) (the disappearance of all target and non-target lesions), Partial Response (PR) (at least a 30% decrease in the sum of the longest diameters \[LD\] of target lesions, taking as a reference the Baseline sum LD), Stable Disease (small changes that do not meet previously given criteria, taking as reference the smallest sum LD since the treatment started), or Progressive Disease (a \>=20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started) was evaluated by an independent review per RECIST, Version 1.
Time to Response	From randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 39 months	Time to response was defined as the time from the start of treatment until the first documented evidence of CR (the disappearance of all target and non-target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD), whichever comes first. CR and PR were evaluated by an independent review per RECIST, Version 1.
Duration of Response (DOR)	From the date of the first documented response (CR or PR) to the date of first documented progression or death due to any cause, assessed up to approximately 39 months	DOR was defined as the time from the first documented evidence of response (CR or PR) until the first documented sign of disease progression (a \>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of \>=1 new lesion) or death, if sooner. CR=the disappearance of all target and non-target lesions. PR=at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD.
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Scores at Day 28 of Cycles 1-4	Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)	FACIT Fatigue Subscale is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The total score range is from 0-52. The higher the score, the lower the fatigue level.
Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Disease-related Symptoms-physical (DRS-P) Domain Score at Day 28 of Cycles 1-4	Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)	Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (Disease-Related Symptoms - Physical (FKSI-DRS-P), Disease-Related Symptoms - Emotional (FKSI-DRS-E), Treatment Side-Effects (FKSI-TSE), Function/Well-Being (FKSI-FWB)) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition.
Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Disease Related Symptoms-emotional (DRS-E) Domain Score at Day 28 of Cycles 1-4	Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)	Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (Disease-Related Symptoms - Physical (FKSI-DRS-P), Disease-Related Symptoms - Emotional (FKSI-DRS-E), Treatment Side-Effects (FKSI-TSE), Function/Well-Being (FKSI-FWB)) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition.
Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Functional Well Being (FWB) Domain Score at Day 28 of Cycles 1-4	Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)	Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (Disease-Related Symptoms - Physical (FKSI-DRS-P), Disease-Related Symptoms - Emotional (FKSI-DRS-E), Treatment Side-Effects (FKSI-TSE), Function/Well-Being (FKSI-FWB)) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition.
Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Total Score at Day 28 of Cycles 1-4	Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)	Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (Disease-Related Symptoms - Physical (FKSI-DRS-P), Disease-Related Symptoms - Emotional (FKSI-DRS-E), Treatment Side-Effects (FKSI-TSE), Function/Well-Being (FKSI-FWB)) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition.
Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Scale Worst Soreness Scores at Day 28 of Cycles 1-4	Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)	The SQLQ scale consists of 5 items that assess the worst mouth and throat, hand, and foot soreness, as well as limitations due to mouth/throat and foot soreness. Participants were asked to assess their worst mouth/throat, hand, and foot soreness by answering the question of In the past 4 weeks, what was your worst mouth/throat, hand, and foot soreness? by using the following 4-point scale: 0, I never had any soreness; 1, I had a little bit of soreness; 2, I had quite a lot of soreness; 3, I had severe soreness. A positive mean change from Baseline represents a worsening of condition.
Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Limitations Due to Mouth and Throat Soreness Score at Day 28 of Cycles 1-4	Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)	The SQLQ consists of 5 items assessing the worst mouth/throat, hand, and foot soreness, and limitations due to mouth/throat and foot soreness. Participants assessed the limitations caused by their mouth/throat soreness by answering the question of In the past 4 weeks, how much did your worst mouth/throat soreness limit you in the following activities: swallowing/eating/drinking/talking/sleeping by using the following 4-point scale: 0, not limited; 1, limited a little; 2, limited a lot; 3, unable to do. The overall limitation score (15=best; 0=worst), based on the individual scores for the 5 activities, is derived as follows: the actual scores were rescored by subtracting the actual score from 3 for each of the 5 categories. A high score indicates less limitation. Change from Baseline was calculated as the assessment week value minus the Baseline value. A negative mean change from Baseline represents a worsening of condition.
Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Limitations Due to Foot Soreness Scores at Day 28 of Cycles 1-4	Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)	The SQLQ consists of 5 items assessing the worst mouth/throat, hand, and foot soreness, and limitations due to mouth/throat and foot soreness. Participants assessed the limitations caused by their foot soreness by answering the question of In the past 4 weeks, how much did your worst foot soreness limit you in each of the following activities: standing/walking/climbing stairs/sleeping/ability to do usual activities by using the following 4-point scale: 0, not limited; 1, limited a little; 2, limited a lot; 3, unable to do. The overall limitation score (15=best; 0=worst), based on the individual scores for the 5 activities, is derived as follows: the actual scores were rescored by subtracting the actual score from 3 for each of the 5 categories. A high score indicates less limitation. Change from Baseline was calculated as the assessment week value minus the Baseline value. A negative mean change from Baseline represents a worsening of condition.
Summary of Analysis for the Cancer Treatment Satisfaction Questionnaire (CTSQ) Score at Day 28 of Cycles 1-4	Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)	The CTSQ assesses 3 domains related to the participant's satisfaction with cancer therapy: Expectations of Therapy (ET), Feelings about Side Effects (FSE), and Satisfaction with Therapy (SWT). Participants shared their thoughts on their cancer therapy (9 questions), their satisfaction with their most recently administered cancer therapy (6 questions), and if they would take the same cancer therapy if given the choice to do so again. All questions were assessed on a 5-point scale; 1, never; 5, always. Scores were averaged and transformed to a 0-100 scale; higher scores represent better treatment satisfaction.
Mean Number of Non-study Medical Visits, Telephone Consultations, Hospital Days, and Emergency Room (ER) Visits Per 30 Days Through Week 24	From Day 1 up to Week 24	Non-study medical visits were defined as the sum of primary care physician visits, nurse practitioner/physician's assistant/nurse visits, and medical or surgical specialist visits. Days hospitalized were defined as the sum of days in the general ward and days in intensive care. The number of telephone consultations and ER visits was assessed via individual questions on the electronic Case Report Form. The endpoint was totaled through Week 24, divided by the number of days on treatment for each participant, then multiplied by 30 days to get the number of visits per 30 days.
Mean Number of Laboratory Visits, Radiology Visits, Home Healthcare Visits, and Medical Procedures at Day 28 of Cycles 1-4	Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)	The number of non-study laboratory visits (NSLVs), non-study radiology visits (NSRVs), and home healthcare visits (HHVs) were each collected as a single question on the eCRF. The number of non-study medical or surgical procedures (MSPs) was defined as the sum of procedures performed at outpatient or physician clinics, as well as those performed during any inpatient hospitalization.
Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Treatment Side Effects (TSE) Domain Score at Day 28 of Cycles 1-4	Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)	Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (Disease-Related Symptoms - Physical (FKSI-DRS-P), Disease-Related Symptoms - Emotional (FKSI-DRS-E), Treatment Side-Effects (FKSI-TSE), Function/Well-Being (FKSI-FWB)) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition.

Other

Measure	Time frame	Description
All Collected Deaths	Pre-treatment deaths: Up to 21 days prior to treatment. On-treatment deaths: Up to 129 months. Post-treatment deaths: up to 152 months.	Pre-treatment deaths were collected from day of participant's informed consent to the day before first dose of study medication. On-treatment deaths were collected from first dose of study medication to 28 days after last dose of study medication (on-treatment), up to approximately 129 months. Deaths were collected in the post treatment survival follow up from 29 days after last dose of study medication until the end of the study, up to approximately 152 months.

Countries

Australia, Canada, China, Germany, Ireland, Italy, Japan, Netherlands, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States

Participant flow

Pre-assignment details

Participants were stratified based on Karnofsky Performance Scale scores (70 or 80; 90 or 100), Baseline levels of lactate dehydrogenase (\>1.5 versus \<=1.5 times the upper limit of normal \[ULN\]), and previous nephrectomy (yes versus no) and were randomized in a 1:1 ratio to receive either pazopanib or sunitinib.

Participants by arm

Arm	Count
Pazopanib 800 mg Participants were administered pazopanib 800 mg (2 x 400 mg tablets) orally OD continuously. Pazopanib was to be taken at least one hour before or at least two hours after a meal. Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.	557
Sunitinib 50 mg Participants were administered sunitinib 50 mg orally once daily in 6-week cycles (4 weeks of treatment, followed by 2 weeks without treatment). Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.	553
Total	1,110

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	20	15
Overall Study	Physician Decision	14	12
Overall Study	Protocol Violation	1	2
Overall Study	Transitioned to another mechanism of continuing pazopanib or sunitinib therapy after 30SEP2013	8	7
Overall Study	Withdrawal by Subject	29	36

Baseline characteristics

Characteristic	Sunitinib 50 mg	Pazopanib 800 mg	Total
Age, Continuous	61.2 Years STANDARD_DEVIATION 10.98	60.9 Years STANDARD_DEVIATION 10.89	61.1 Years STANDARD_DEVIATION 10.93
Race/Ethnicity, Customized African American/African Heritage	5 Participants	10 Participants	15 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants	3 Participants	3 Participants
Race/Ethnicity, Customized American Indian or Alaska Native & White	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Asian	188 Participants	194 Participants	382 Participants
Race/Ethnicity, Customized Unknown	1 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized White	358 Participants	349 Participants	707 Participants
Sex: Female, Male Female	138 Participants	159 Participants	297 Participants
Sex: Female, Male Male	415 Participants	398 Participants	813 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	25 / 557	22 / 553	310 / 529	312 / 526
other Total, other adverse events	541 / 554	535 / 548	0 / 0	0 / 0
serious Total, serious adverse events	242 / 554	227 / 548	0 / 0	0 / 0

Outcome results

Primary

Progression-free Survival (PFS)

PFS was defined as the interval between the date of randomization and the earliest date of progressive disease (PD), as defined by the Independent Review Committee (IRC), or death due to any cause. The IRC defined PD per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1. Per RECIST, PD is defined as a \>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of \>=1 new lesion.

Time frame: From randomization until the earliest date of disease progression or date of death from any cause, assessed up to approximately 39 months

Population: Intent-to-Treat (ITT) Population. Analysis was based on the assigned randomized treatment, not on the actual treatment received/not received. Participants who had neither progressed nor died were censored at the date of the last adequate tumor assessment at the time of the cut-off.

Arm	Measure	Value (MEDIAN)
Pazopanib 800 mg	Progression-free Survival (PFS)	8.4 Months
Sunitinib 50 mg	Progression-free Survival (PFS)	9.5 Months

95% CI: [0.8982, 1.2195]

Secondary

Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Scores at Day 28 of Cycles 1-4

FACIT Fatigue Subscale is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The total score range is from 0-52. The higher the score, the lower the fatigue level.