Tinzaparin in Treating Patients With Metastatic Kidney Cancer That Cannot Be Removed By Surgery

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2007 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00293501
First received: February 16, 2006
Last updated: November 5, 2013
Last verified: February 2007
  Purpose

RATIONALE: Tinzaparin may stop the growth of kidney cancer by blocking blood flow to the tumor.

PURPOSE: This phase I/II trial is studying the side effects of tinzaparin and to see how well it works in treating patients with metastatic kidney cancer that cannot be removed by surgery.


Condition Intervention Phase
Kidney Cancer
Drug: tinzaparin sodium
Phase 1
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Tinzaparin (Innohep), a Low Molecular Weight Heparin (LMWH) for Treatment of Advanced Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Blood markers or coagulation as measured by plasma prothrombin F1.2, thrombin-antithrombin complexes, and D-dimers at 2 weeks, 2 months and 6 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Blood markers of angiogenesis as measured by serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) at 2 weeks, 2 months, and 6 months [ Designated as safety issue: No ]
  • Venous thromboembolism as measured by clinical evaluation at 6 months [ Designated as safety issue: No ]
  • Progression free survival as measured by clinical evaluation at 4 months [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: December 2005
Estimated Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the effect of tinzaparin sodium on fibrin formation (prothrombin fragment F1.2), thrombin generation (thrombin-antithrombin complexes), and fibrinolysis (D-Dimer) from baseline to 2 weeks and at nadir or disease progression in patients with unresectable metastatic renal cell carcinoma (RCC).

Secondary

  • Determine the effect of tinzaparin sodium treatment on circulating angiogenesis markers, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).
  • Determine the proportion of patients developing venous thromboembolism and hemorrhage.
  • Determine the tolerability of tinzaparin sodium treatment for up to 6 months in these patients.
  • Establish the feasibility of undertaking a multicenter renal cell carcinoma trial with specialized coagulation test collection, shipping, and processing.
  • Obtain more accurate and specific mean, median, and variability in biomarker data in advanced RCC patients treated with tinzaparin sodium for purposes of planning larger future trials.
  • Estimate the progression-free survival at 4 months in patients treated with tinzaparin sodium.
  • Correlate progression-free survival with changes in markers of coagulation activation or angiogenesis.
  • Correlate the anticoagulant activity of tinzaparin sodium (anti-Xa activity) with change in coagulation markers, angiogenesis markers, and progression-free survival.

OUTLINE: This is an open-label, pilot, multicenter study.

Patients receive a treatment dose of tinzaparin sodium subcutaneously (SC) once daily for 14 days followed by a prophylactic dose of tinzaparin sodium SC once daily for up to 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed renal cell carcinoma of clear cell histology

    • Tumors of mixed histology eligible if ≥ 50% of tumor has clear cell histology
    • No nonclear cell histologies, collecting duct tumors, oncocytomas, or transitional cell tumors
  • Metastatic and unresectable disease that is clinically extending beyond the regional lymph nodes (histological confirmation not required)

    • Patients who are inoperable for their primary tumor representing the sole site of disease are ineligible
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 2 cm by conventional techniques OR ≥ 1 cm by spiral CT scan
  • No known brain metastases

PATIENT CHARACTERISTICS:

  • Expected survival > 2 months
  • CALGB (ECOG/ZUBROD) performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Hemoglobin ≥ 10 g/dL
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST/ALT ≤ 1.5 times ULN
  • Creatinine ≤ 1.5 times ULN
  • INR ≤ 1.5 times control value
  • PTT < 1.5 times control value
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Patients must be able to receive subcutaneous injections at home
  • No other primary malignancy in the past 5 years other than basal cell carcinoma or carcinoma in situ of the cervix that has been curatively treated and is associated with a less than 30% risk of relapse in the next 5 years
  • No signs or symptoms of bleeding within 4 the past weeks
  • No known bleeding diathesis or high risk for bleeding due to any condition, including trauma within the past 4 weeks, active current bleeding, or hemorrhagic stroke or intraocular bleeding within the past 6 months
  • No active thromboembolism highly likely to require anticoagulation during the study period
  • No known or suspected history of type II heparin-induced thrombocytopenia
  • No allergy or hypersensitivity to heparin, tinzaparin sodium, pork products, sulfite, or benzyl alcohol
  • No uncontrolled severe intercurrent illness, including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • No uncontrolled arterial hypertension, history of gastrointestinal ulceration, and/or bleeding in the past 4 weeks
  • No diabetic retinopathy or history of retinal hemorrhage
  • Not pregnant or nursing
  • HIV-positive patients are allowed

PRIOR CONCURRENT THERAPY:

  • No treatment with anticoagulation lasting > 1 month in the past 6 months
  • No anticoagulation, including treatment with a low molecular weight heparin, at any time within the past month
  • More than 4 weeks since prior surgery, radiation therapy, immunotherapy, or chemotherapy
  • Recovered from prior therapy
  • No other concurrent investigational agents
  • No other concurrent anticoagulation therapy, including oral anticoagulants, thrombolytic agents, or any form of heparin

    • Concurrent antiplatelet agents allowed
  • No spinal or epidural puncture, anesthesia, or post-operative indwelling epidural catheters within the past 48 hours
  • No other concurrent anticancer agents or therapies
  • No concurrent sex hormones except for postmenopausal hormone replacement
  • No concurrent chemotherapy or immunotherapy
  • No concurrent palliative radiotherapy
  • Concurrent urgent use of corticosteroids allowed
  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: NCT00293501

Locations
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, Vermont
Vermont Cancer Center at University of Vermont
Burlington, Vermont, United States, 05405-0110
Sponsors and Collaborators
University of Vermont
Investigators
Study Chair: Deborah L. Ornstein, MD Yale University
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00293501     History of Changes
Other Study ID Numbers: CDR0000459794, VCC-0403, VCC-05-040
Study First Received: February 16, 2006
Last Updated: November 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
clear cell renal cell carcinoma
stage IV renal cell cancer
recurrent renal cell cancer

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Kidney Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Tinzaparin
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014