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

NCT01061411 | Completed Phase 1 DMC

• 2 other identifiers: I 145508NCI-2009-01694
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 4

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

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

  Up to 4 years

• Incidence of toxicities for the combination of dalteparin and sunitinib malate

  Toxicities will be summarized by tabulation. Summaries will be made across all types of toxicities and by grade and type.

  Up to 4 weeks after last treatment

• Recommended dosing for the combination of dalteparin and sunitinib malate

  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.

  Up to 4 weeks

Secondary Outcomes (3)

• 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

  Up to 4 weeks after last treatment

• Overall survival

  Up to 4 years

• TTP

  Up to 4 years

Other Outcomes (2)

• Changes in angiogenesis parameters in blood

  Baseline to 4 weeks after last treatment

• Changes in plasma coagulation parameters

  Baseline to 4 weeks after last treatment

Study Arms (1)

Treatment (sunitinib malate, dalteparin)

EXPERIMENTAL

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; Other: Pharmacological Study; Drug: Sunitinib Malate

Interventions

Dalteparin DRUG

Given SC

Treatment (sunitinib malate, dalteparin)

Pharmacological Study OTHER

Correlative studies

Treatment (sunitinib malate, dalteparin)

Sunitinib Malate DRUG

Given PO

Also known as: SU011248, SU11248, sunitinib, Sutent

Treatment (sunitinib malate, dalteparin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Pfizer: collaborator

Study Sites (4)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Academ Zienkenhuis Bij De University

Amsterdam, 1007 MB, Netherlands

Location

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Dalteparin; Sunitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Saby George

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2010
• First Posted: February 3, 2010
• Study Start: February 6, 2010
• Primary Completion: October 14, 2015
• Study Completion: April 21, 2017
• Last Updated: August 5, 2022

Record last verified: 2022-08

Locations

NL (2); US (2)