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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
N/A
Open (Enrolling)
Both
Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer

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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


PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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
(NED).

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
years.


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
randomization

- 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
randomization

- 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:

Interventional

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:

No

Principal Investigator

Leonard Appleman

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-00723

NCT ID:

NCT01575548

Start Date:

August 2012

Completion Date:

Related Keywords:

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

Name

Location

University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
Hurley Medical CenterFlint, Michigan  48503
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Loyola University Medical CenterMaywood, Illinois  60153
Rapid City Regional HospitalRapid City, South Dakota  57709
Waukesha Memorial HospitalWaukesha, Wisconsin  53188
Munson Medical CenterTraverse City, Michigan  49684
Bozeman Deaconess HospitalBozeman, Montana  59715
Kalispell Medical OncologyKalispell, Montana  59901
Kalispell Regional Medical CenterKalispell, Montana  59901
Adena Regional Medical CenterChillicothe, Ohio  54601
Grady Memorial HospitalDelaware, Ohio  43015
Fairfield Medical CenterLancaster, Ohio  43130
Welch Cancer CenterSheridan, Wyoming  82801
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
Hematology and Oncology AssociatesChicago, Illinois  60611
Mecosta County Medical CenterBig Rapids, Michigan  49307
Saint Francis Medical CenterCape Girardeau, Missouri  63701
Grandview HospitalDayton, Ohio  45405
Allenmore HospitalTacoma, Washington  98411-0414
Hematology Oncology Associates of Illinois-Highland ParkHighland Park, Illinois  60035
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Northeast Georgia Medical CenterGainesville, Georgia  30501
Saint Luke's HospitalChesterfield, Missouri  63017
Miami Valley HospitalDayton, Ohio  45409
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
Wayne HospitalGreenville, Ohio  45331
Knox Community HospitalMount Vernon, Ohio  43050
Providence Centralia HospitalCentralia, Washington  98531-9027
Rocky Mountain OncologyCasper, Wyoming  82609
Greene Memorial HospitalXenia, Ohio  45385
Wellmont Holston Valley Hospital and Medical CenterKingsport, Tennessee  37662
City of HopeDuarte, California  91010
University of PittsburghPittsburgh, Pennsylvania  15261
Northwestern UniversityChicago, Illinois  60611
Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Riverside Methodist HospitalColumbus, Ohio  43214
Licking Memorial HospitalNewark, Ohio  43055-2899
Columbus CCOPColumbus, Ohio  43206
Montana Cancer Consortium CCOPBillings, Montana  59101
Huntsman Cancer Institute/University of UtahSalt Lake City, Utah  84112
Oregon Health and Science UniversityPortland, Oregon  97201
Montana Cancer SpecialistsMissoula, Montana  59807-7877
Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
Saint Joseph's-Candler Health SystemSavannah, Georgia  31405
Provena Saint Mary's HospitalKankakee, Illinois  60901
North Shore Hematology OncologyLibertyville, Illinois  60048
Good Samaritan Regional Medical CenterMt. Vernon, Illinois  62864
Hematology Oncology Associates of Illinois - SkokieSkokie, Illinois  60076
Reid Hospital and Health Care ServicesRichmond, Indiana  47374
McFarland ClinicAmes, Iowa  50010
Mercy Medical Center - North IowaMason City, Iowa  50401
Mercy Medical Center-Sioux CitySioux City, Iowa  51104
Saint Luke's Regional Medical CenterSioux City, Iowa  51104
Michigan Cancer Research Consortium Community Clinical Oncology ProgramAnn Arbor, Michigan  48106
Oakwood HospitalDearborn, Michigan  48123
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Grand Rapids Clinical Oncology ProgramGrand Rapids, Michigan  49503
Saint Mary's Health CareGrand Rapids, Michigan  49503
Spectrum Health at Butterworth CampusGrand Rapids, Michigan  49503
Allegiance HealthJackson, Michigan  49201
Sparrow HospitalLansing, Michigan  48912
Saint Mary Mercy HospitalLivonia, Michigan  48154
Mercy Health Partners-Mercy CampusMuskegon, Michigan  49443
Saint Joseph Mercy OaklandPontiac, Michigan  48341-2985
Saint Joseph Mercy Port HuronPort Huron, Michigan  48060
Saint Mary's of MichiganSaginaw, Michigan  48601
Saint John Macomb-Oakland HospitalWarren, Michigan  48093
Saint Louis-Cape Girardeau CCOPSaint Louis, Missouri  63141
Saint John's Mercy Medical CenterSaint Louis, Missouri  63141
Hematology-Oncology Centers of the Northern Rockies PCBillings, Montana  59101
Saint Vincent HealthcareBillings, Montana  59101
Billings ClinicBillings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment CenterButte, Montana  59701
Benefis Healthcare- Sletten Cancer InstituteGreat Falls, Montana  59405
Saint Peter's Community HospitalHelena, Montana  59601
Saint Patrick Hospital - Community HospitalMissoula, Montana  59802
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
Orange Regional Medical CenterMiddletown, New York  10940
Wayne Memorial HospitalGoldsboro, North Carolina  27534
Kinston Medical Specialists PAKinston, North Carolina  28501
Doctors HospitalColumbus, Ohio  43228
Grant Medical CenterColumbus, Ohio  43215
Mount Carmel Health Center WestColumbus, Ohio  43222
Good Samaritan Hospital - DaytonDayton, Ohio  45406
Dayton CCOPDayton, Ohio  45429
Samaritan North Health CenterDayton, Ohio  45415
Blanchard Valley HospitalFindlay, Ohio  45840
Atrium Medical Center-Middletown Regional HospitalFranklin, Ohio  45005-1066
Kettering Medical CenterKettering, Ohio  45429
Marietta Memorial HospitalMarietta, Ohio  45750
Upper Valley Medical CenterTroy, Ohio  45373
Saint Ann's HospitalWesterville, Ohio  43081
Genesis HealthCare SystemZanesville, Ohio  43701
Natalie W Bryant Cancer CenterTulsa, Oklahoma  74136
Pottstown Memorial Medical CenterPottstown, Pennsylvania  19464
Southwest VA Regional Cancer CenterNorton, Virginia  24273
Auburn Regional Medical CenterAuburn, Washington  98002
Saint Francis HospitalFederal Way, Washington  98003
Providence - Saint Peter HospitalOlympia, Washington  98506-5166
Good Samaritan Community HospitalPuyallup, Washington  98372
Northwest CCOPTacoma, Washington  98405
Multicare Health SystemTacoma, Washington  98415
Saint Clare HospitalTacoma, Washington  98499
Saint Joseph Medical CenterTacoma, Washington  98405
Oconomowoc Memorial Hospital-ProHealth Care IncOconomowoc, Wisconsin  53066-3896
Moores University of California San Diego Cancer CenterLA Jolla, California  92093
University of Michigan University HospitalAnn Arbor, Michigan  48109
Erlanger Medical CenterChattanooga, Tennessee  37403
University of Tennessee - KnoxvilleKnoxville, Tennessee  37920
Saint Joseph Regional Medical CenterLewiston, Idaho  83501
Spectrum Health Reed City HospitalReed City, Michigan  49677
The Mark H Zangmeister CenterColumbus, Ohio  43219
Southern Ohio Medical CenterPortsmouth, Ohio  45662
Cancer Care Associates-MercyOklahoma City, Oklahoma  73120
Overlake Hospital Medical CenterBellevue, Washington  98004
Providence Regional Cancer PartnershipEverett, Washington  98201
Gundersen LutheranLa Crosse, Wisconsin  54601
Siouxland Hematology Oncology AssociatesSioux City, Iowa  51101
Franciscan St. Francis HealthIndianapolis, Indiana  46237
Eastern Cooperative Oncology GroupBoston, Massachusetts  02215
Illinois Cancer Specialists-NilesNiles, Illinois  60714
Bronson Battle CreekBattle Creek, Michigan  49017
Springfield Regional Medical CenterSpringfield, Ohio  45505
Saint Louis Cancer and Breast Institute-South CitySaint Louis, Missouri  63109
Blue Ridge Medical Specialists PCBristol, Tennessee  37620
Cancer Care Associates-NormanNorman, Oklahoma  73071
D N Greenwald CenterMukwonago, Wisconsin  53149
Idaho Urologic Institute PAMeridian, Idaho  83642
Wellmont Bristol Regional Medical CenterBristol, Tennessee  37620