Tandutinib in Treating Patients Who Have Undergone Surgery for Metastatic Kidney Cancer
Condition: Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Cancer; Stage IV Renal Cell Cancer
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: tandutinib; laboratory biomarker analysis
Intervention description: Given orally, 500 mg bid daily; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well tandutinib works in treating patients who have
      undergone surgery for metastatic kidney cancer. Tandutinib may stop the growth of kidney
      cancer by blocking some of the enzymes needed for cell growth and by blocking blood flow to
      the tumor. Giving tandutinib after surgery may kill any tumor cells that remain after
      surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed RCC of clear cell histology; subjects must have a component
             of conventional clear cell RCC with or without sarcomatoid features

          -  Patients must have evidence of metastatic disease and must have had a cytoreductive
             nephrectomy at least 28 days prior to first day of treatment

          -  Archival tissue from nephrectomy must be available for correlative studies

          -  Patients must have measurable disease, defined by RECIST criteria

          -  Patients must have received at least one prior FDA approved therapy for metastatic
             renal cell carcinoma with either Sutent, or Nexavar, and may have received up to three
             prior systemic therapies for metastatic disease; prior cytokine therapy is also
             permitted

          -  Prior systemic therapy with other antiangiogenic agents such as Thalidomide,
             Bevacizumab, or AG013736 is permitted

          -  Patients must have a life expectancy of >= 3 months

          -  Patients must have an ECOG performance status of 0-1 (Karnofsky >= 70%)

          -  Patients must be at least 4 weeks from radiation therapy and recovered from all
             related toxicity

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin >= 8.5 g/dl

          -  Total Bilirubin =< 1.5 X institutional upper limit of normal

          -  AST (SGOT)/ALT (SGPT) =< 3.5 X institutional upper limit of normal

          -  Alkaline phosphatase =< 2.5 ULN (=< 10 x ULN in presence of bone metastasis)

          -  Serum calcium of =< 12 mg/dl

          -  Creatinine =< 1.5 X institutional upper limit of normal

          -  INR =< 1.5, except for subjects receiving warfarin therapy; for subjects who are
             receiving warfarin for prophylaxis or treatment of thrombosis, INR values should be
             carefully monitored while patients are on study

          -  Electrocardiogram (12-lead) with cQTC < 500 msec using the Bazett's formula

          -  Absence of significant effusions and/or ascites

          -  No major surgery requiring general anesthesia within the past 28 days

          -  Patients may not have had brain metastasis

          -  Eligibility of patients receiving any medications or substances known to affect or
             with the potential to affect the activity or pharmacokinetics of MLN518 will be
             determined following review of their case by the Principal Investigator; because
             MLN518 is a substrate of the P-glycoprotein (P-gp) drug efflux pump, co-
             administration of agents that inhibit or induce this mechanism may alter exposure to
             MLN518

          -  The effects of MLN518 on the developing human fetus at the recommended therapeutic
             dose are unknown; for this reason and because receptor tyrosine kinase inhibitors are
             known to be teratogenic, women of child-bearing potential and men must agree to use
             adequate contraception (hormonal or barrier method of birth control; abstinence) prior
             to study entry and for the duration of study participation; should a woman become
             pregnant or suspect she is pregnant while participating in this study, she should
             inform her treating physician immediately; sexually active patients must continue to
             use contraception for three months after completion of study therapy

          -  All patients must be informed of the investigational nature of this study and must
             provide written informed consent in accordance with institutional and federal
             guidelines; a copy of the informed consent document signed by the patient must be
             given to the patient

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Patients may not be receiving any other investigational agents

          -  Patients may not be co-medicated with an agent that causes QTc prolongation

          -  Patients with a mean QTc > 500 msec using the Bazett's formula taken from the
             screening electrocardiogram or history of familial long QT syndrome are ineligible

          -  Left ventricular ejection fraction (LVEF) < 40%

          -  Myocardial infarction within 6 months of enrollment or New York Heart Association
             (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled
             ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active
             conduction system abnormalities

          -  Ongoing vomiting, or nausea >= grade 2 (NCI CTCAE v3.0)

          -  Patients with any condition (e.g., gastrointestinal tract disease resulting in an
             inability to take oral medication or a requirement for IV alimentation, prior surgical
             procedures affecting absorption, or active peptic ulcer disease) that impairs their
             ability to swallow pills or absorb oral medications are excluded

          -  Known or suspected primary muscular or neuromuscular disease (e.g., muscular
             dystrophy, myasthenia gravis)

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to MLN518 such as Tarceva™, Iressa® and Cardura® XL

          -  Patients with any CNS metastases or uncontrolled seizure disorder

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infections or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Any malignancy other than a renal cell carcinoma, with the following exceptions:

               -  Basal or squamous cell carcinomas of the skin

               -  Carcinoma in-situ of the uterine cervix

               -  Any malignancy treated with curative intent and in complete remission for > 3
                  years

          -  Patients with organ allografts

          -  Patients with non-clear cell carcinoma i.e., papillary, collecting duct, or
             chromophobe

          -  Pregnant women are excluded from this study because MLN518 is a receptor tyrosine
             kinase inhibitor with the potential for teratogenic or abortifacient effects; because
             there is an unknown but potential risk for adverse events in nursing infants secondary
             to treatment of the mother with MLN518, breastfeeding should be discontinued if the
             mother is treated with MLN518

          -  HIV-positive patients on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with MLN518; in addition, these
             patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy; appropriate studies will be undertaken in patients
             receiving combination antiretroviral therapy when indicated

          -  Inability to comply with study and/or follow-up procedures