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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Pfizer
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01061411
First received: February 1, 2010
Last updated: April 4, 2016
Last verified: April 2016
  Purpose
This phase I trial studies the side effects and best dose of dalteparin when given together with sunitinib malate in treating patients with kidney cancer that has spread to other parts of the body or cannot be removed by surgery. 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.

Condition Intervention Phase
Clear Cell Sarcoma of the Kidney
Recurrent Renal Cell Carcinoma
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
Drug: Dalteparin
Other: Pharmacological Study
Drug: Sunitinib Malate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Early signs of clinical activity of the combination of sunitinib malate and dalteparin [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Incidence of toxicities 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.

  • Recommended dosing for the combination of dalteparin and sunitinib malate [ Time Frame: Up to 4 weeks ] [ 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.


Secondary Outcome Measures:
  • Clinical response rate of dalteparin and sunitinib malate, determined as the proportion of treated patients who had partial or complete response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 [ Time Frame: Up to 4 weeks after last treatment ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Described in all patients using Kaplan-Meier curves.

  • TTP [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Described in all patients using Kaplan-Meier curves.


Other Outcome Measures:
  • Changes in angiogenesis parameters in blood [ Time Frame: Baseline to 4 weeks after last treatment ] [ Designated as safety issue: No ]
    Each will be explored to determine if transformations (e.g. log or square-root) are necessary to achieve normality. For each of baseline and changes, exploratory plots (e.g. histograms, boxplots) will be created and means will be estimated along with 95% confidence intervals. Wilcoxon signed-rank tests will be used to determine whether or not the data shows evidence of changes from baseline.

  • Changes in plasma coagulation parameters [ Time Frame: Baseline to 4 weeks after last treatment ] [ Designated as safety issue: No ]
    Each will be explored to determine if transformations (e.g. log or square-root) are necessary to achieve normality. For each of baseline and changes, exploratory plots (e.g. histograms, boxplots) will be created and means will be estimated along with 95% confidence intervals. Wilcoxon signed-rank tests will be used to determine whether or not the data shows evidence of changes from baseline.


Enrollment: 16
Study Start Date: February 2010
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (sunitinib malate, dalteparin)
Patients receive sunitinib malate PO QD in weeks 1-4 and dalteparin 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.
Drug: Dalteparin
Given SC
Other: Pharmacological Study
Correlative studies
Drug: Sunitinib Malate
Given PO
Other Names:
  • SU011248
  • SU11248
  • sunitinib
  • Sutent

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 (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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01061411

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Netherlands
Academ Zienkenhuis Bij De University
Amsterdam, Netherlands, 1007 MB
VU University Medical Center
Amsterdam, Netherlands, 1081 HV
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Pfizer
Investigators
Principal Investigator: Saby George Roswell Park Cancer Institute
  More Information

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01061411     History of Changes
Other Study ID Numbers: I 145508  NCI-2009-01694  I 145508  P30CA016056 
Study First Received: February 1, 2010
Last Updated: April 4, 2016
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Sunitinib
Carcinoma
Carcinoma, Renal Cell
Sarcoma, Clear Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Heparin, Low-Molecular-Weight
Dalteparin
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 21, 2016