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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Pfizer
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01061411
First received: February 1, 2010
Last updated: August 6, 2014
Last verified: August 2014

February 1, 2010
August 6, 2014
February 2010
September 2014   (final data collection date for primary outcome measure)
  • Recommended dosing for the combination of dalteparin and sunitinib malate [ Time Frame: Within the first 4 weeks of combination therapy ] [ Designated as safety issue: Yes ]
    The maximally tolerated dose (MTD) will be the highest dose at which < 33% of patients (=< 2 out of 6 patients) suffer from dose limiting toxicities (DLTs) related to the combination treatment.
  • Evaluate safety and tolerability for the combination of dalteparin and sunitinib malate [ Time Frame: Up to 4 weeks after last treatment ] [ Designated as safety issue: Yes ]
    Toxicities will be summarized by tabulation. Summaries will be made across all types of toxicities and by grade and type.
  • Early signs of clinical activity of the combination of sunitinib malate and dalteparin [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • PHASE I: To find the highest dose of Dalteparin that can be given with Sunitinib without causing severe side effects, and test the safety of Dalteparin in combination with Sunitinib [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • PHASE II: To study whether the dose of Dalteparin and Sunitinib that was found to be safe in Phase I part of this study is of benefit against tumor in patients with advanced renal cell cancer (kidney cancer) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01061411 on ClinicalTrials.gov Archive Site
  • Clinical response rate of dalteparin and sunitinib malate [ Time Frame: Up to 4 weeks after last treatment ] [ Designated as safety issue: No ]
  • TTP and overall survival among patients receiving dalteparin plus sunitinib malate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • PHASE I: Determine the efficacy of this combination treatment against kidney cancer. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • PHASE II: To study whether the dose that was found to be safe in Phase I part of this study of Dalteparin in combination with Sunitinib can be given safely in a larger number of patients [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Dalteparin and Sunitinib Malate as First-Line Therapy in Treating Patients With Metastatic or Unresectable Kidney Cancer
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

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

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.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Clear Cell Sarcoma of the Kidney
  • Recurrent Renal Cell Cancer
  • Stage III Renal Cell Cancer
  • Stage IV Renal Cell Cancer
  • Drug: dalteparin
    Given SC
    Other Names:
    • DAL
    • dalteparin sodium
    • Fragmin
  • Drug: sunitinib malate
    Given PO
    Other Names:
    • SU11248
    • sunitinib
    • Sutent
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
  • Procedure: dynamic contrast-enhanced magnetic resonance imaging
    Correlative studies
    Other Name: DCE-MRI
  • Other: immunohistochemistry staining method
    Correlative studies
    Other Name: immunohistochemistry
Experimental: Treatment (anticoagulant and enzyme inhibitor)
Patients receive sunitinib malate PO once daily in weeks 1-4 and dalteparin 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.
Interventions:
  • Drug: dalteparin
  • Drug: sunitinib malate
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
  • Procedure: dynamic contrast-enhanced magnetic resonance imaging
  • Other: immunohistochemistry staining method
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
16
Not Provided
September 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have histologically confirmed metastatic or unresectable renal cell carcinoma
  • 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Netherlands
 
NCT01061411
I 145508, NCI-2009-01694
Yes
Roswell Park Cancer Institute
Roswell Park Cancer Institute
  • National Cancer Institute (NCI)
  • Pfizer
Principal Investigator: Roberto Pili Roswell Park Cancer Institute
Roswell Park Cancer Institute
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP