Know Cancer

forgot password

Randomized, Double-Blind Phase III Study of Pazopanib vs. Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease Following Metastatectomy

Phase 3
18 Years
Open (Enrolling)
Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer

Thank you

Trial Information

Randomized, Double-Blind Phase III Study of Pazopanib vs. Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease Following Metastatectomy


I. To evaluate disease-free survival, defined as the time from randomization to the
development of recurrent disease, second primary cancer (other than localized breast,
localized prostate, or non-melanoma skin cancer), or death from any cause, of patients with
metastatic renal cell carcinoma (RCC) with no evidence of disease following metastasectomy
with pazopanib hydrochloride (pazopanib) as compared to placebo.


I. To describe the overall survival of patients with advanced RCC randomly assigned to
receive placebo or pazopanib for one year following metastasectomy to no evidence of disease

II. To describe treatment- and (at recurrence) disease-related adverse events in the two
treatment arms III. To analyze quality-adjusted time without symptoms of disease or
treatment (Q-TWiST) for subjects in the two treatment arms.

IV. To characterize changes in patient-reported fatigue and (at recurrence) kidney
cancer-related symptoms during and following treatment with pazopanib compared to placebo.

V. To explore the association between plasma trough levels of pazopanib and disease-free and
overall survival.

VI. To prospectively bank preserved tissue from primary tumors and associated metastatic
sites in patients with RCC.

OUTLINE: Patients are randomized to 1of 2 treatment arms.

ARM I: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28.
Treatment repeats every 28 days for up to 13 courses in the absence of disease progression
or unacceptable toxicity.

ARM II: Patients receive placebo PO QD on days 1-28. Treatment repeats every 28 days for up
to 13 courses in the absence of disease progression or unacceptable toxicity.

Patients may undergo blood sample collection at baseline and periodically during treatment
for pharmacokinetic and future correlative studies. Tumor tissue samples may also be
collected. Patients complete questionnaires related to mobility, self-care, usual
activities, pain/discomfort, and anxiety/depression, along with a question about global
health (EQ-5D), the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale,
the Patient-Reported Outcome Measurement Information System (PROMIS)-Fatigue scale, and the
Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI-15) at baseline and
periodically during study.

After completion of study treatment, patients are followed up every 3 months for up to 10

Inclusion Criteria:

- Patient must have pathologically confirmed renal cell carcinoma with a clear cell
component; pure papillary and chromophobe histologies are excluded; there must be
pathologic confirmation of metastatic disease in the resected metastasectomy specimen

- Patient must have undergone nephrectomy or partial nephrectomy to remove primary
renal cell carcinoma (at any time in the past)

- Patient must have undergone surgical resection to remove one or more sites of
metastatic disease, with successful removal of all known sites 2-12 weeks prior to

- Eligible patient must have no evidence of disease on post-operative imaging (computed
tomography [CT] and/or magnetic resonance imaging [MRI]) conducted within 4 weeks
prior to randomization

- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 or 1 at the time of randomization

- Absolute granulocyte count > 1,500/mcL

- Platelets > 100,000/mcL

- Total bilirubin < 1.5 times institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
< 2.5 times upper limit of normal (ULN)

- Calculated creatinine clearance (CrCl) > 30 mL/min

- Women must not be pregnant or breast-feeding

- All females of childbearing potential must have a blood test or urine study
within 2 weeks prior to randomization to rule out pregnancy; a female of
childbearing potential is any woman, regardless of sexual orientation or whether
they have undergone tubal ligation, who meets the following criteria: has not
undergone a hysterectomy or bilateral oophorectomy; or has not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any
time in the preceding 24 consecutive months)

- Women of childbearing potential and sexually active males must be strongly advised to
use an accepted and effective method of contraception or to abstain from sexual
intercourse for the duration of their participation in the study

- Patient must be able to swallow pills and have no significant impairment in
gastrointestinal absorption including history of gastric bypass surgery

- Patient must have no history of allergic reactions attributed to compounds of similar
chemical or biologic composition to pazopanib

- Patient must have no uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements

- Patient must have a QTc interval on electrocardiogram (ECG) =< 0.48 seconds by
Bazett's calculation (=< Common Terminology Criteria for Adverse Events [ CTCAE] v.4
Grade 2) prior to randomization

- Patient must have a systolic blood pressure =<140 mm Hg and diastolic blood pressure
must be =< 90 mm Hg, measured within 4 weeks prior to randomization; initiation or
adjustment of anti-hypertensives prior to starting study treatment is allowed

- Patient must not have serious or non-healing wound, ulcer, or bone fracture at the
time of randomization

- Patient must have no history of abdominal fistula, gastrointestinal perforation, or
intra-abdominal abscess within 4 weeks prior to randomization

- Patient must have no history of cerebrovascular accident (CVA) within 6 months of

- Patient must have no history of myocardial infarction, hospital admission for
unstable angina, cardiac angioplasty, or stenting within 6 months of randomization

- Patient must have no history of venous thrombosis within 12 weeks of randomization

- Patient must not have history of hemoptysis in excess of 2.5 mL (½ teaspoon) within
8weeks prior to randomization

- Patient must be able to receive either computed tomography (CT) with intravenously
(IV) contrast or magnetic resonance imaging (MRI) with gadolinium

- Patient must not have received any prior or concurrent systemic therapy for RCC;
adjuvant placebo administration is permitted

- Patient cannot be taking strong CYP3A4 inhibitors such as:

- Antibiotics: clarithromycin, telithromycin, troleandomycin

- Human immunodeficiency virus (HIV) antiviral protease inhibitors: ritonavir,
indinavir, saquinavir, nelfinavir, amprenavir, lopinavir

- Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole

- Antidepressants: nefazodone

- Patient must not be taking drugs known to prolong the QTc interval; such drugs should
be discontinued at least 1 week prior to randomization

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Disease-free survival (DFS)

Outcome Description:

Spearman's Rank Correlation Coefficient will be calculated to test whether there is a relationship between pazopanib hydrochloride trough levels and DFS.

Outcome Time Frame:

Time from randomization to recurrence, development of second primary cancer, or death from any cause, assessed up to 10 years

Safety Issue:


Principal Investigator

Leonard Appleman

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

August 2012

Completion Date:

Related Keywords:

  • Clear Cell Renal Cell Carcinoma
  • Stage IV Renal Cell Cancer
  • Carcinoma
  • Carcinoma, Renal Cell



University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
University of Mississippi Medical Center Jackson, Mississippi  39216-4505
Washington University School of Medicine Saint Louis, Missouri  63110
Hurley Medical Center Flint, Michigan  48503
Genesys Hurley Cancer Institute Flint, Michigan  48503
Bronson Methodist Hospital Kalamazoo, Michigan  49007
West Michigan Cancer Center Kalamazoo, Michigan  49007-3731
Borgess Medical Center Kalamazooaa, Michigan  49001
Loyola University Medical Center Maywood, Illinois  60153
Rapid City Regional Hospital Rapid City, South Dakota  57709
Waukesha Memorial Hospital Waukesha, Wisconsin  53188
Munson Medical Center Traverse City, Michigan  49684
Bozeman Deaconess Hospital Bozeman, Montana  59715
Kalispell Medical Oncology Kalispell, Montana  59901
Kalispell Regional Medical Center Kalispell, Montana  59901
Adena Regional Medical Center Chillicothe, Ohio  54601
Grady Memorial Hospital Delaware, Ohio  43015
Fairfield Medical Center Lancaster, Ohio  43130
Welch Cancer Center Sheridan, Wyoming  82801
Methodist Estabrook Cancer Center Omaha, Nebraska  68114-4199
Hematology and Oncology Associates Chicago, Illinois  60611
Mecosta County Medical Center Big Rapids, Michigan  49307
Saint Francis Medical Center Cape Girardeau, Missouri  63701
Grandview Hospital Dayton, Ohio  45405
Allenmore Hospital Tacoma, Washington  98411-0414
Hematology Oncology Associates of Illinois-Highland Park Highland Park, Illinois  60035
Saint Joseph Mercy Hospital Ann Arbor, Michigan  48106
Northeast Georgia Medical Center Gainesville, Georgia  30501
Saint Luke's Hospital Chesterfield, Missouri  63017
Miami Valley Hospital Dayton, Ohio  45409
Bozeman Deaconess Cancer Center Bozeman, Montana  59715
Wayne Hospital Greenville, Ohio  45331
Knox Community Hospital Mount Vernon, Ohio  43050
Providence Centralia Hospital Centralia, Washington  98531-9027
Rocky Mountain Oncology Casper, Wyoming  82609
Greene Memorial Hospital Xenia, Ohio  45385
Wellmont Holston Valley Hospital and Medical Center Kingsport, Tennessee  37662
City of Hope Duarte, California  91010
University of Pittsburgh Pittsburgh, Pennsylvania  15261
Northwestern University Chicago, Illinois  60611
Saint Alphonsus Regional Medical Center Boise, Idaho  83706
Riverside Methodist Hospital Columbus, Ohio  43214
Licking Memorial Hospital Newark, Ohio  43055-2899
Columbus CCOP Columbus, Ohio  43206
Montana Cancer Consortium CCOP Billings, Montana  59101
Huntsman Cancer Institute/University of Utah Salt Lake City, Utah  84112
Oregon Health and Science University Portland, Oregon  97201
Montana Cancer Specialists Missoula, Montana  59807-7877
Saint Francis Hospital and Medical Center Hartford, Connecticut  06105
Saint Joseph's-Candler Health System Savannah, Georgia  31405
Provena Saint Mary's Hospital Kankakee, Illinois  60901
North Shore Hematology Oncology Libertyville, Illinois  60048
Good Samaritan Regional Medical Center Mt. Vernon, Illinois  62864
Hematology Oncology Associates of Illinois - Skokie Skokie, Illinois  60076
Reid Hospital and Health Care Services Richmond, Indiana  47374
McFarland Clinic Ames, Iowa  50010
Mercy Medical Center - North Iowa Mason City, Iowa  50401
Mercy Medical Center-Sioux City Sioux City, Iowa  51104
Saint Luke's Regional Medical Center Sioux City, Iowa  51104
Michigan Cancer Research Consortium Community Clinical Oncology Program Ann Arbor, Michigan  48106
Oakwood Hospital Dearborn, Michigan  48123
Saint John Hospital and Medical Center Detroit, Michigan  48236
Grand Rapids Clinical Oncology Program Grand Rapids, Michigan  49503
Saint Mary's Health Care Grand Rapids, Michigan  49503
Spectrum Health at Butterworth Campus Grand Rapids, Michigan  49503
Allegiance Health Jackson, Michigan  49201
Sparrow Hospital Lansing, Michigan  48912
Saint Mary Mercy Hospital Livonia, Michigan  48154
Mercy Health Partners-Mercy Campus Muskegon, Michigan  49443
Saint Joseph Mercy Oakland Pontiac, Michigan  48341-2985
Saint Joseph Mercy Port Huron Port Huron, Michigan  48060
Saint Mary's of Michigan Saginaw, Michigan  48601
Saint John Macomb-Oakland Hospital Warren, Michigan  48093
Saint Louis-Cape Girardeau CCOP Saint Louis, Missouri  63141
Saint John's Mercy Medical Center Saint Louis, Missouri  63141
Hematology-Oncology Centers of the Northern Rockies PC Billings, Montana  59101
Saint Vincent Healthcare Billings, Montana  59101
Billings Clinic Billings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment Center Butte, Montana  59701
Benefis Healthcare- Sletten Cancer Institute Great Falls, Montana  59405
Saint Peter's Community Hospital Helena, Montana  59601
Saint Patrick Hospital - Community Hospital Missoula, Montana  59802
Nevada Cancer Research Foundation CCOP Las Vegas, Nevada  89106
Orange Regional Medical Center Middletown, New York  10940
Wayne Memorial Hospital Goldsboro, North Carolina  27534
Kinston Medical Specialists PA Kinston, North Carolina  28501
Doctors Hospital Columbus, Ohio  43228
Grant Medical Center Columbus, Ohio  43215
Mount Carmel Health Center West Columbus, Ohio  43222
Good Samaritan Hospital - Dayton Dayton, Ohio  45406
Dayton CCOP Dayton, Ohio  45429
Samaritan North Health Center Dayton, Ohio  45415
Blanchard Valley Hospital Findlay, Ohio  45840
Atrium Medical Center-Middletown Regional Hospital Franklin, Ohio  45005-1066
Kettering Medical Center Kettering, Ohio  45429
Marietta Memorial Hospital Marietta, Ohio  45750
Upper Valley Medical Center Troy, Ohio  45373
Saint Ann's Hospital Westerville, Ohio  43081
Genesis HealthCare System Zanesville, Ohio  43701
Natalie W Bryant Cancer Center Tulsa, Oklahoma  74136
Pottstown Memorial Medical Center Pottstown, Pennsylvania  19464
Southwest VA Regional Cancer Center Norton, Virginia  24273
Auburn Regional Medical Center Auburn, Washington  98002
Saint Francis Hospital Federal Way, Washington  98003
Providence - Saint Peter Hospital Olympia, Washington  98506-5166
Good Samaritan Community Hospital Puyallup, Washington  98372
Northwest CCOP Tacoma, Washington  98405
Multicare Health System Tacoma, Washington  98415
Saint Clare Hospital Tacoma, Washington  98499
Saint Joseph Medical Center Tacoma, Washington  98405
Oconomowoc Memorial Hospital-ProHealth Care Inc Oconomowoc, Wisconsin  53066-3896
Moores University of California San Diego Cancer Center LA Jolla, California  92093
University of Michigan University Hospital Ann Arbor, Michigan  48109
Erlanger Medical Center Chattanooga, Tennessee  37403
University of Tennessee - Knoxville Knoxville, Tennessee  37920
Saint Joseph Regional Medical Center Lewiston, Idaho  83501
Spectrum Health Reed City Hospital Reed City, Michigan  49677
The Mark H Zangmeister Center Columbus, Ohio  43219
Southern Ohio Medical Center Portsmouth, Ohio  45662
Cancer Care Associates-Mercy Oklahoma City, Oklahoma  73120
Overlake Hospital Medical Center Bellevue, Washington  98004
Providence Regional Cancer Partnership Everett, Washington  98201
Gundersen Lutheran La Crosse, Wisconsin  54601
Siouxland Hematology Oncology Associates Sioux City, Iowa  51101
Franciscan St. Francis Health Indianapolis, Indiana  46237
Eastern Cooperative Oncology Group Boston, Massachusetts  02215
Illinois Cancer Specialists-Niles Niles, Illinois  60714
Bronson Battle Creek Battle Creek, Michigan  49017
Springfield Regional Medical Center Springfield, Ohio  45505
Saint Louis Cancer and Breast Institute-South City Saint Louis, Missouri  63109
Blue Ridge Medical Specialists PC Bristol, Tennessee  37620
Cancer Care Associates-Norman Norman, Oklahoma  73071
D N Greenwald Center Mukwonago, Wisconsin  53149
Idaho Urologic Institute PA Meridian, Idaho  83642
Wellmont Bristol Regional Medical Center Bristol, Tennessee  37620