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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
Open (Enrolling)
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


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



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