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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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Clear Cell Sarcoma of the Kidney, Recurrent Renal Cell Cancer, Stage III Renal Cell Cancer, Stage IV Renal Cell Cancer

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Trial Information

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


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.


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:

Prior therapy with Sunitinib 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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Recommended dosing for the combination of dalteparin and sunitinib malate

Outcome Description:

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.

Outcome Time Frame:

Within the first 4 weeks of combination therapy

Safety Issue:

Yes

Principal Investigator

Roberto Pili

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

I 145508

NCT ID:

NCT01061411

Start Date:

February 2010

Completion Date:

Related Keywords:

  • Clear Cell Sarcoma of the Kidney
  • Recurrent Renal Cell Cancer
  • Stage III Renal Cell Cancer
  • Stage IV Renal Cell Cancer
  • Carcinoma, Renal Cell
  • Sarcoma, Clear Cell
  • Sarcoma

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
City of HopeDuarte, California  91010
Johns Hopkins University CCOPBaltimore, Maryland  21287