Pazopanib Hydrochloride Before Surgery in Treating Patients With Kidney Cancer
Condition: Clear Cell Renal Cell Carcinoma; Stage I Renal Cell Cancer; Stage II Renal Cell Cancer; Stage III Renal Cell Cancer
MeSH terms: Carcinoma, Renal Cell
Intervention: pazopanib hydrochloride; therapeutic conventional surgery
Intervention description: Oral pazopanib hydrochloride once daily for up to 18 weeks in the absence of disease progression or unacceptable toxicity.; Patients undergo either partial or radical nephrectomy at least 7 days after completion of pazopanib hydrochloride.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      RATIONALE: Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth. Giving pazopanib hydrochloride before surgery may make the
      tumor smaller and reduce the amount of normal tissue that needs to be removed.

      PURPOSE: This phase II trial is studying how well pazopanib hydrochloride works when given
      before surgery in treating patients with kidney cancer.
    

Eligibility criteria:

        Inclusion

          -  Histologically or cytologically proven renal carcinoma with a clear cell component

          -  Need for optimized partial nephrectomy based on one or more of the following criteria
             (all applicable criteria should be recorded and one criterion designated as the
             primary reason):

               -  Functional or anatomic solitary kidney, bilateral tumors, or pre-existing chronic
                  kidney disease (CKD; estimated glomerular filtration rate (GFR) by
                  Cockcroft-Gault formula < 60 mL/min) and tumor amenable to partial nephrectomy,
                  but partial nephrectomy would result in estimated GFR < 30 mL/min; this
                  estimation will be based on current estimated GFR, nuclear renal scan to estimate
                  relative renal function (if 2 kidneys), tumor location(s), and amount of normal
                  renal parenchyma that would need to be removed with nephrectomy

               -  Radical nephrectomy is required for tumor excision; however, it would result in
                  estimated GFR < 30 mL/min; this estimation will be based on current estimated
                  GFR, nuclear renal scan to estimate relative renal function (if 2 kidneys), tumor
                  location(s), and amount of normal renal parenchyma that would need to be removed
                  with radical nephrectomy

               -  Greater than 30% likelihood that a partial nephrectomy would be associated with a
                  high risk of significant morbidity (e.g. hemorrhage) due to proximity to the
                  renal hilum (within 3 mm of main renal artery, renal vein or their primary
                  branches) and/or other anatomic factors as determined by the operating surgeon

               -  Renal nephrometry score of 10-12

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Karnofsky >= 70%

          -  Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) =<
             2.5 x laboratory upper limit of normal (ULN)

          -  Serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x
             laboratory upper limit of normal (ULN)

          -  Total serum bilirubin =< 1.5 x ULN

          -  Absolute neutrophil count (ANC) >= 1500/uL

          -  Platelets >= 100,000/uL

          -  Hemoglobin >= 9.0 g/dL (no transfusion permitted within 1 week)

          -  Serum creatinine =< 2.5 mg/dL

          -  Urine to protein to creatinine (UPC) ratio < 1; if UPC > 1, then a 24-hour urine
             protein must be assessed; subjects must have a 24-hour urine protein value < 1g to be
             eligible

          -  Prothrombin time (PT) or international normalized ratio (INR) and partial
             thromboplastin time (PTT) =< 1.2 X upper limit of normal (ULN)

          -  Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests, and other study procedures; subjects must provide written informed consent
             prior to performance of study-specific procedures or assessments, and must be willing
             to comply with treatment and follow up

          -  A female is eligible to enter and participate in this study if she is of:

          -  Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),
             including any female who has had: a hysterectomy; a bilateral oophorectomy
             (ovariectomy); a bilateral tubal ligation; is post-menopausal

          -  Subjects not using hormone replacement therapy (HRT) must have experienced total
             cessation of menses for >= 1 year and be greater than 45 years in age, OR, in
             questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and an
             estradiol value < 40pg/mL (< 140 pmol/L)

          -  Subjects using HRT must have experienced total cessation of menses for >= 1 year and
             be greater than 45 years of age OR have had documented evidence of menopause based on
             FSH and estradiol concentrations prior to initiation of HRT

          -  Childbearing potential, including any female who has had a negative serum pregnancy
             test within 2 weeks prior to the first dose of study treatment, preferably as close to
             the first dose as possible, and agrees to use adequate contraception; GlaxoSmithKlein
             (GSK) acceptable contraceptive methods, when used consistently and in accordance with
             both the product label and the instructions of the physician, are as follows: an
             intrauterine device with a documented failure rate of less than 1% per year;
             vasectomized partner who is sterile prior to the female subject's entry and is the
             sole sexual partner for that female; complete abstinence from sexual intercourse for
             14 days before exposure to investigational product, through the dosing period, and for
             at least 21 days after the last dose of investigational product; or double-barrier
             contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm
             with spermicide; or male condom and diaphragm with spermicide)

        Exclusion

          -  Prior systemic treatment for RCC

          -  Evidence of any distant metastatic disease

          -  Evidence of bleeding diathesis or coagulopathy; patients with hematuria from the
             primary renal tumor are eligible provided all other eligibility criteria are met

          -  History of any one or more of the following cardiovascular conditions within the past
             6 months: cardiac angioplasty or stenting; myocardial infarction; unstable angina;
             coronary artery bypass graft surgery; symptomatic peripheral vascular disease

          -  Class III or IV congestive heart failure, as defined by the New York Heart Association
             (NYHA)

          -  Prolongation of corrected QT interval (QTc) > 480 msecs

          -  Hypertension that cannot be controlled by medications to < 160/90 mmHg

          -  History of cerebrovascular accident, pulmonary embolism or untreated deep venous
             thrombosis (DVT) within the past 6 months (Note: subjects with recent DVT who have
             been treated with therapeutic anti-coagulating agents for at least 6 weeks are
             eligible)

          -  Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
             presence of any non-healing wound, fracture, or ulcer (procedures such as catheter
             placement not considered to be major)

          -  Hemoptysis within 6 weeks of first dose of study drug

          -  Any serious and/or unstable pre-existing medical, psychiatric, or other condition that
             could interfere with subject's safety, provision of informed consent, or compliance to
             study procedures

          -  Unable or unwilling to discontinue use of prohibited medications for at least 14 days
             or five half-lives of a drug (whichever is longer) prior to the first dose of study
             drug and for the duration of the study

          -  Clinically significant gastrointestinal abnormalities that may increase the risk for
             GI bleeding including, but not limited to: active peptic ulcer disease; known
             intraluminal metastatic lesion/s with suspected bleeding; inflammatory bowel disease
             (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with
             increased risk of perforation; history of abdominal fistula, gastrointestinal
             perforation, or intra abdominal abscess within 28 days prior to beginning study
             treatment

          -  Clinically significant gastrointestinal abnormalities that may affect absorption of
             investigational product including, but not limited to: malabsorption syndrome; major
             resection of the stomach or small bowel

          -  Prior major surgery or trauma (NOT including biopsy of renal mass; also procedures
             such as catheter placement not considered to be major) within 28 days prior to first
             dose of study drug and/or presence of any non-healing wound, fracture, or ulcer

          -  Presence of uncontrolled infection

          -  Other severe acute or chronic medical or psychiatric conditions or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the patient inappropriate for entry into
             this study