Pazopanib Hydrochloride in Treating Patients With Metastatic Kidney Cancer Who Have No Evidence of Disease After Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01575548
First received: April 10, 2012
Last updated: September 16, 2014
Last verified: April 2014
  Purpose

This randomized phase III trial studies how well pazopanib hydrochloride works compared to placebo in treating patients with metastatic kidney cancer who have no evidence of disease after surgery. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.


Condition Intervention Phase
Clear Cell Renal Cell Carcinoma
Recurrent Renal Cell Cancer
Stage IV Renal Cell Cancer
Drug: pazopanib hydrochloride
Other: placebo
Other: quality-of-life assessment
Other: questionnaire administration
Other: pharmacological study
Phase 3

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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Disease-free survival (DFS) [ Time Frame: Time from randomization to recurrence, development of second primary cancer, or death from any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
    Spearman's Rank Correlation Coefficient will be calculated to test whether there is a relationship between pazopanib hydrochloride trough levels and DFS.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Time from randomization to date of death, assessed up to 10 years ] [ Designated as safety issue: No ]
    Overall survival for each treatment group will be partitioned into three health states: toxicity (TOX), time without symptoms of disease or toxicity (TWiST), and recurrence (REC).

  • Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]
  • Change in Q-TWiST between the two arms as assessed by the European Quality of Life 5-Dimensions (EQ-5D) [ Time Frame: From baseline to up to 10 years ] [ Designated as safety issue: No ]
    The mean amount of time in each state will be estimated using the method of Kaplan and Meier (1958).

  • Change in fatigue as assessed by Patient Reported Outcome Measurement Information System (PROMIS) Fatigue and Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue subscales [ Time Frame: From baseline to 15 months ] [ Designated as safety issue: No ]
  • Change in kidney cancer-related symptoms as assessed by the Functional Assessment of Cancer Therapy-Kidney Cancer Symptom Index (FKSI-15) [ Time Frame: From baseline to 15 months ] [ Designated as safety issue: No ]
  • Plasma trough levels of pazopanib hydrochloride [ Time Frame: Day 1 of course 2 ] [ Designated as safety issue: No ]
    The association of plasma trough levels of pazopanib hydrochloride with disease-free and overall survival will be explored.


Estimated Enrollment: 180
Study Start Date: August 2012
Estimated Primary Completion Date: August 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride 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.
Drug: pazopanib hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Placebo Comparator: Arm II (placebo)
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.
Other: placebo
Given PO
Other Name: PLCB
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate disease-free survival with pazopanib (pazopanib hydrochloride) as compared to placebo, 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 for patients with metastatic renal cell carcinoma (RCC) with no evidence of disease following metastatectomy.

SECONDARY OBJECTIVES:

I. To describe the overall survival of patients with advanced RCC randomly assigned to receive placebo or pazopanib for one year following metastatectomy 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.

After completion of study treatment, patients are followed up every 3 months for the first two years, every 6 months for the next 3 years, and then annually through 10 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 metastatectomy 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; any number of prior metastatectomies may have been performed in the past, so long as the most recent procedure was within the 12 weeks of registration; the most recent procedure may be nephrectomy for a renal primary tumor
  • Patients with synchronous disease at initial diagnosis must have metastatic (M1) disease (American Joint Committee on Cancer [AJCC] 7th edition T1-4N0-1M1)
  • Positive surgical margins are permitted if the surgeon confirms complete resection of gross metastatic disease, and post-operative scans are negative
  • Patients presenting with metachronous disease may have distant metastases, regional lymph node or renal bed recurrence; recurrences at a partial nephrectomy resection site are not eligible if it is the only site of disease
  • Patients presenting with tumors within the kidneys (multiple synchronous or single/multiple metachronous) are not eligible if there are no extrarenal sites of disease (i.e. potential multifocal primary disease)
  • Patient must have no evidence of disease on post-operative imaging:

    • A computed tomography (CT) of the chest must be obtained within 4 weeks prior to randomization with or without contrast
    • A CT of the abdomen/pelvis must be obtained within 4 weeks prior to randomization with intravenous (IV) contrast (oral contrast may be added at the radiologist's discretion); an MRI of the abdomen/pelvis with gadolinium may be substituted for the CT if the CT with IV contrast is contra-indicated
    • An MRI of the brain with and without gadolinium must be done within 8 weeks prior to randomization; a CT of the brain with and without IV contrast is permitted if MRI is contra-indicated (i.e., pacemaker)
  • Patient must not have received any prior or concurrent systemic therapy for RCC; adjuvant placebo administration is permitted
  • Patient must have no active peptic ulcer disease
  • Patient must have no active inflammatory bowel disease
  • Patient must have no New York Heart Association (NYHA) class II or greater congestive heart failure
  • Patient must have no prior history or current clinically apparent central nervous system metastases
  • 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
  • Subjects must have a urine protein/creatinine (UPC) ratio < 1; if UPC >= 1, then a 24-hour urine total protein must be obtained; subjects must have a 24-hour urine protein value < 1g to be eligible; use of urine dipstick for renal function assessment is not acceptable
  • Women must not be pregnant or breast-feeding
  • 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; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately
  • 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 corrected QT (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 mmHg and diastolic blood pressure must be =< 90 mmHg, 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 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 have history of hemoptysis in excess of 2.5 mL (1/2 teaspoon) within 8 weeks prior to randomization
  • Patient must not be taking drugs known to prolong the QTc interval; such drugs should be discontinued at least 5 half-lives prior to randomization
  • Patients must not have any history of other cancer within 3 years from time of randomization with the exception of basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or resected non-invasive (Ta) urothelial carcinoma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01575548

  Show 287 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Leonard Appleman Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01575548     History of Changes
Other Study ID Numbers: NCI-2012-00723, NCI-2012-00723, CDR0000730383, ECOG-E2810, E2810, E2810, U10CA180820, U10CA021115
Study First Received: April 10, 2012
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on September 18, 2014