Dalteparin and Sunitinib Malate as First-Line Therapy in Treating Patients With Kidney Cancer That is Metastatic or Cannot Be Removed by Surgery

PRIMARY OBJECTIVES:

I. To determine the recommended dosing for the combination of sunitinib (sunitinib malate)
and dalteparin in patients with metastatic renal cell carcinoma.

II. To evaluate safety and tolerability for the combination of sunitinib and dalteparin in
patients with metastatic renal cell carcinoma.

III. To determine early signs of clinical activity of the combination of sunitinib and
dalteparin in patients with metastatic renal cell carcinoma.

SECONDARY OBJECTIVES:

I. To determine the clinical response rate of sunitinib and dalteparin in patients with
metastatic renal cell carcinoma.

II. To determine time-to-progression (TTP) and overall survival amongst patients with
metastatic renal cell carcinoma receiving sunitinib and dalteparin.

III. To determine the effect of sunitinib alone and dalteparin alone compared to the
combination of dalteparin plus sunitinib on plasma coagulation parameters.

IV. To determine the effect of sunitinib alone and dalteparin alone compared to the
combination of dalteparin plus sunitinib on angiogenesis parameters in blood.

OUTLINE: This is a dose-escalation study of dalteparin.

Patients receive sunitinib malate orally (PO) once daily (QD) in weeks 1-4 and dalteparin
subcutaneously (SC) QD in week 6 during course 1. In all subsequent courses, patients
receive sunitinib malate PO QD in weeks 1-4 and dalteparin SC QD in weeks 1-6. Courses
repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 3
months for 3 years.

Inclusion Criteria:

- Patients must have histologically confirmed renal cell carcinoma that is metastatic
or unresectable

- Renal carcinoma patients with predominant clear-cell histology are eligible;
papillary renal cell carcinoma, oncocytoma, collecting duct tumors and transitional
cell carcinoma are NOT eligible

- No prior systemic treatments for metastatic disease are permitted, including
antiangiogenic therapy, immunotherapy, chemotherapy and investigational therapy

- Prior palliative radiation to metastatic lesion(s) is permitted, provided there is at
least one measurable and/or evaluable lesion(s) that has not been irradiated

- Radiation therapy must be completed > 4 weeks prior to registration

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension as >= 20 mm with conventional
techniques or as approximately >= 10 mm with spiral computed tomography (CT) scan
(Response Evaluation Criteria in Solid Tumors [RECIST] 1.0 criteria)

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Leukocytes > 3,000/mm^3

- Absolute neutrophil count > 1,500/mm^3

- Platelets > 100,000/mm^3

- Total bilirubin < 1.5 x laboratory upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/
alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x
laboratory ULN

- Creatinine < 1.5 x laboratory ULN

- Prothrombin time (PT)/international normalized ratio (INR) < 1.5

- Urine protein < 1+; if > 1+, 24 hour urine protein should be obtained and should be <
1000 mg

- Women of child-bearing potential 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

- Ability to understand and the willingness to sign a written informed consent document

- Except for Dalteparin that will be administered as a study drug, the patients should
not take any other anticoagulants or antiplatelet agents during the study, including
but not limited to nonsteroidal anti-inflammatory drugs (NSAID) (any dose of
aspirin), warfarin or other anticoagulants

Exclusion Criteria:

- Patients may not be receiving any other investigational agents

- Patients with known central nervous system (CNS) metastases; patients should have a
head CT/magnetic resonance imaging (MRI) within 4 weeks prior to treatment
initiation; any imaging abnormality indicative of CNS metastases will exclude the
patient from the study

- Patients with a "currently active" second malignancy other than non-melanoma skin
cancers are not eligible; patients are not considered to have a "currently active"
malignancy if they have completed anti-cancer therapy and are considered by their
physician to be at less than 30% risk of relapse

- Patients with a large (> 2 cm) pulmonary lesion involving the trachea or one of the
main bronchus and any endobronchial lesion

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to dalteparin

- Evidence of bleeding diathesis within last 6 months

- Serious or non-healing wound, ulcer or bone fracture or active peptic ulceration

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure (New York Association class II, III,
or IV), angina pectoris requiring nitrate therapy, recent myocardial infarction (<
the last 6 months), cardiac arrhythmia, history of cerebrovascular accident (CVA)
within 6 months (thrombotic or hemorrhagic), hypertension (defined as blood pressure
of > 160 mmHg systolic and/or > 90 mm Hg diastolic on medication), hemorrhagic
retinopathy, history of peripheral vascular disease, or psychiatric illness/social
situations that would limit compliance with study requirements

- Patients with an ejection fraction < 50% by multi gated acquisition scan (MUGA) scan
are not eligible

- Pregnant women are excluded from this study

- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
within 28 days prior to day 1 therapy

- Invasive procedures defined as:

- Major surgical procedure, open biopsy, or significant traumatic injury within 6
weeks prior to day 1 therapy

- Anticipation of need for major surgical procedures during the course of the
study

- Core biopsy within 7 days prior to start therapy