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NCT Number: NCT00720941

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

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.

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Key information

Conditions

Carcinoma, Renal Cell Adenocarcinoma Carcinoma Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Neoplasms Male Urogenital Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Novartis Investigative Site, Camperdown, New South Wales, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Pazopanib

Drug

800 mg administered once daily orally continuous dosing

Other names: GW786034

Sunitinib

Drug

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

Primary outcomes

  1. Progression-free Survival (PFS)

    Time frame: 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 outcomes

  1. Overall Survival

    Time frame: 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.

  2. Overall Response Rate (ORR) as Assessed by Independent Review

    Time frame: 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.

  3. Time to Response

    Time frame: 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.

  4. Duration of Response (DOR)

    Time frame: 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.

  5. Number of Participants With Adverse Events

    Time frame: 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.

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

    Time frame: 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.

  7. 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

    Time frame: 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.

  8. 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

    Time frame: 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.

  9. 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

    Time frame: 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.

  10. 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

    Time frame: 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.

  11. Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Total Score at Day 28 of Cycles 1-4

    Time frame: 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.

  12. Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Scale Worst Soreness Scores at Day 28 of Cycles 1-4

    Time frame: 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.

  13. 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

    Time frame: 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.

  14. Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Limitations Due to Foot Soreness Scores at Day 28 of Cycles 1-4

    Time frame: 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.

  15. Summary of Analysis for the Cancer Treatment Satisfaction Questionnaire (CTSQ) Score at Day 28 of Cycles 1-4

    Time frame: 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.

  16. Mean Number of Non-study Medical Visits, Telephone Consultations, Hospital Days, and Emergency Room (ER) Visits Per 30 Days Through Week 24

    Time frame: 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.

  17. Mean Number of Laboratory Visits, Radiology Visits, Home Healthcare Visits, and Medical Procedures at Day 28 of Cycles 1-4

    Time frame: 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.

Other outcomes

  1. All Collected Deaths

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

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

Acronym: COMPARZ

Important dates

Study start
2008
Primary completion
2012
Study completion
2021
First posted
Jul 23, 2008
Registry last updated
Mar 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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