Pazopanib Hydrochloride in Treating Patients With Metastatic Kidney Cancer
Condition: Carcinoma of the Collecting Ducts of Bellini; Chromophobe Renal Cell Carcinoma; Kidney Medullary Carcinoma; Kidney Oncocytoma; Metastatic Renal Cell Cancer; Papillary Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma; Stage IV Renal Cell Cancer
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Carcinoma, Medullary
Intervention: Pazopanib Hydrochloride
Intervention description: Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well pazopanib hydrochloride works in treating patients with
      kidney cancer that has spread to other places in the body (metastatic). Pazopanib
      hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for
      cell growth. Pazopanib hydrochloride may also stop the growth of kidney cancer by blocking
      blood flow to the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological confirmation of non-clear cell renal cancer (including chromophilic
             [papillary], chromophobic, oncocytic, sarcomatoid, collecting duct [Bellini's duct]),
             translocation-type carcinoma or medullary renal cell carcinoma

          -  Up to one prior treatment for metastatic non clear cell carcinoma is allowed prior to
             registration as long as the agent used to treat was not pazopanib

          -  Measurable or non-measurable metastatic disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

          -  Absolute neutrophil count (ANC) >= 1500

          -  Platelets (PLT) >= 100,000

          -  Hemoglobin (HgB) > 9.0 g/dL; NOTE: subjects may not have had a transfusion within 7
             days of registration

          -  Total bilirubin < 1.5 x upper limit of normal (ULN); NOTE: concomitant elevations in
             bilirubin above 1.0 x ULN is not permitted

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN;
             NOTE: concomitant elevations in ALT/AST above 1.0 x ULN is not permitted

          -  Urine protein to creatinine ratio (UPC) < 1; NOTE: if UPC >= 1, then a 24-hour urine
             protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be
             eligible

          -  Prothrombin time (PT) or international normalized ratio (INR) =< 1.2 x ULN; NOTE:
             subjects receiving anticoagulant therapy are eligible if their INR is stable and
             within the recommended range for the desired level of anticoagulation

          -  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 < 40 pg/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, =< 7 days prior to registration

               -  Agrees to use adequate contraception; acceptable contraceptive methods, when used
                  consistently and in accordance with both the product label and the instructions
                  of the physician, are as follows:

                    -  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

                    -  Oral contraceptive, either combined or progesterone alone

                    -  Intrauterine device (IUD) or intrauterine system (IUS) with a documented
                       failure rate of less than 1% per year

                    -  Male partner sterilization (vasectomy with documentation of azoospermia)
                       prior to the female subject's entry into the study, and this male is the
                       sole partner for that subject

                    -  Double barrier method: condom and an occlusive cap (diaphragm or
                       cervical/vault caps) with a vaginal spermicidal agent
                       (foam/gel/film/cream/suppository)

          -  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;
             procedures conducted as part of the subject's routine clinical management (e.g., blood
             count, imaging study) and obtained prior to signing of informed consent may be
             utilized for screening or baseline purposes provided these procedures are conducted as
             specified in the protocol

          -  Willing to return to Mayo Clinic enrolling institution for follow-up

        Exclusion Criteria:

          -  Any of the following:

               -  Nursing women

               -  Pregnant women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Immunocompromised patients (other than that related to the use of corticosteroids)
             including patients known to be human immunodeficiency virus (HIV) positive

          -  Prior history of receiving pazopanib treatments

          -  Uncontrolled intercurrent illness including, but not limited to:

               -  Ongoing or active infection

               -  Symptomatic anemia, uncontrolled hypertension (defined as systolic blood pressure
                  [SBP] of >= 140 mmHg or diastolic blood pressure [DBP] of >= 90mmHg)

               -  Symptomatic congestive heart failure as defined by the New York Heart Association
                  (NYHA); does not exclude class III congestive heart failure (CHF)

               -  Previously treated with therapies that are known to negatively impact cardiac
                  function (e.g. prior treatment with anthracyclines)

               -  Unstable angina pectoris

               -  Cardiac arrhythmia

               -  Evidence of active bleeding or bleeding diathesis

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

               -  Or any other serious uncontrolled medical disorders in the opinion of the
                  investigator

          -  History of cerebrovascular accident including transient ischemic attack (TIA),
             myocardial infarction, pulmonary embolism or untreated deep venous thrombosis (DVT),
             coronary artery bypass graft surgery within 6 months prior to registration; Note:
             subjects with recent DVT who have been treated with therapeutic anti-coagulating
             agents for at least 6 weeks are eligible

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm

          -  Other active malignancy =< 5 years prior to registration; EXCEPTIONS: non-melanotic
             skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior
             malignancy, they must not be receiving other specific treatment for their cancer

          -  History or clinical evidence of central nervous system (CNS) metastases or
             leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS
             metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure
             medication for 6 months prior to first dose of study drug; screening with CNS imaging
             studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required
             only if clinically indicated or if the subject has a history of CNS metastases

          -  Clinically significant gastrointestinal abnormalities that may increase the risk for
             gastrointestinal bleeding including, but not limited to:

               -  Active peptic ulcer disease

               -  Known intraluminal metastatic lesion/s with risk of 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 =< 28 days prior to registration

               -  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

          -  Corrected QT interval (QTc) > 480 msecs using Bazett's formula

          -  Receiving any medications or substances with risk of torsades de pointes; Note:
             medications or substances on the list "Drugs with Risk of Torsades de Pointes" are
             prohibited; medications or substances on the list "Drugs with Possible or Conditional
             Risk of Torsades de Pointes" may be used while on study with extreme caution and
             careful monitoring

          -  Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels and/or
             hemoptysis in excess of 2.5 mL (or one half teaspoon) =< 8 weeks of registration

          -  Treatment with any of the following anti-cancer therapies: radiation therapy, surgery
             or tumor embolization, chemotherapy, immunotherapy, biologic therapy, investigational
             therapy or hormonal therapy =< 14 days prior to registration

          -  Prior autologous or allogeneic organ or tissue transplantation

          -  Elective or planned major surgery to be performed during the course of the trial

          -  Receiving any medications or substances that are strong or moderate inhibitors of
             cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); use of the strong or
             moderate inhibitors are prohibited =< 7 days prior to registration

          -  Receiving any medications or substances that are inducers of CYP3A4; use of inducers
             are prohibited =< 7 days prior to registration