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Dalteparin and Sunitinib Malate as First-Line Therapy in Treating Patients With Metastatic or Unresectable Kidney Cancer

Information source: Roswell Park Cancer Institute
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Clear Cell Sarcoma of the Kidney; Recurrent Renal Cell Cancer; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer

Intervention: dalteparin (Drug); sunitinib malate (Drug); laboratory biomarker analysis (Other); pharmacological study (Other); dynamic contrast-enhanced magnetic resonance imaging (Procedure); immunohistochemistry staining method (Other)

Phase: Phase 1

Status: Active, not recruiting

Sponsored by: Roswell Park Cancer Institute

Official(s) and/or principal investigator(s):
Roberto Pili, Principal Investigator, Affiliation: Roswell Park Cancer Institute


This phase I trial is studying the side effects and best dose of dalteparin when given together with sunitinib malate in treating patients with metastatic or unresectable kidney cancer. Anticoagulants, such as dalteparin, help prevent blood clots and have been shown to increase survival in patients with cancer. Anticoagulants may also prevent the formation of new blood vessels. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by inhibiting new blood vessels and blocking blood flow to the tumor. Giving dalteparin together with sunitinib malate may starve tumors and kill more tumor cells

Clinical Details

Official title: Phase I Study of Dalteparin, A Low Molecular Weight Heparin (LMWH), in Combination With Sunitinib (SU11248), an Oral, Selective Multi-targeted Tyrosine Kinase Inhibitor, as First Line Treatment, in Patients With Metastatic Renal Cell Carcinoma

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Recommended dosing for the combination of dalteparin and sunitinib malate

Evaluate safety and tolerability for the combination of dalteparin and sunitinib malate

Early signs of clinical activity of the combination of sunitinib malate and dalteparin

Secondary outcome:

Clinical response rate of dalteparin and sunitinib malate

TTP and overall survival among patients receiving dalteparin plus sunitinib malate

Detailed description: 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 in weeks 1-4 and dalteparin subcutaneously (SC) once daily in week 6 during course 1. In all subsequent courses, patients receive sunitinib malate PO once daily in weeks 1-4 and dalteparin SC once daily 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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria:

- Patients must have histologically confirmed metastatic or unresectable renal cell


- 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 glutamic pyruvic 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 because sunitinib is an angiogenesis

inhibitor agent with the potential for teratogenic or abortion inducing effects

- 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

Locations and Contacts

Academ Zienkenhuis Bij De University, Amsterdam 1007 MB, Netherlands

VU University Medical Center, Amsterdam 1081 HV, Netherlands

City of Hope, Duarte, California 91010, United States

Roswell Park Cancer Institute, Buffalo, New York 14263, United States

Additional Information

Starting date: February 2010
Last updated: October 14, 2014

Page last updated: August 23, 2015

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