Breast Cancer Clinical Trial

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

Summary

This randomized phase III trial studies how well pazopanib hydrochloride works compared to placebo in treating patients with kidney cancer that has spread to other parts of the body and 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.

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Full 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 metastasectomy.

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 A: 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 B: 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 up to 10 years.

View Eligibility Criteria

Eligibility 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 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; any number of prior metastasectomies 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

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 magnetic resonance imaging (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 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 x institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x 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 < 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable
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: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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; 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 a corrected QT (QTc) interval on electrocardiogram (ECG) =< 0.48 seconds by Bazett's calculation (=< Common Terminology Criteria for Adverse Events [CTCAE] version [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

Exclusion Criteria:

Patients presenting with tumors within the kidneys (multiple synchronous or single/multiple metachronous) if there are no extrarenal sites of disease (i.e. potential multifocal primary disease)
Prior or concurrent systemic therapy for RCC; adjuvant placebo administration is permitted
Active peptic ulcer disease
Active inflammatory bowel disease
New York Heart Association (NYHA) class II or greater congestive heart failure
History or current clinically apparent central nervous system metastases
Pregnant or breast-feeding
History of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib
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
Serious or non-healing wound, ulcer, or bone fracture at the time of randomization
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to randomization
History of cerebrovascular accident (CVA) within 6 months of randomization
History of myocardial infarction, hospital admission for unstable angina, cardiac angioplasty or stenting within 6 months of randomization
History of venous thrombosis within 12 weeks of randomization

Taking strong cytochrome P450, family 3, subfamily A, polypeptide 4 (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
History of hemoptysis in excess of 2.5 mL (1/2 teaspoon) within 8 weeks prior to randomization
Taking drugs known to prolong the QTc interval; such drugs should be discontinued at least 5 half-lives prior to randomization
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

Study is for people with:

Breast Cancer

Phase:

Phase 3

Estimated Enrollment:

129

Study ID:

NCT01575548

Recruitment Status:

Active, not recruiting

Sponsor:

National Cancer Institute (NCI)

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How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 3

Estimated Enrollment:

129

Study ID:

NCT01575548

Recruitment Status:

Active, not recruiting

Sponsor:


National Cancer Institute (NCI)

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