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

Kidney Cancer Clinical Trial

Official title:

A Phase I/II Trial of Tinzaparin (Innohep), a Low Molecular Weight Heparin (LMWH) for Treatment of Advanced Renal Cell Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00293501
• Other study ID #: CDR0000459794
• Secondary ID: VCC-0403VCC-05-0
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: February 16, 2006
• Last updated: November 5, 2013
• Start date: December 2005

Study information

• Verified date: February 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 35
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Kidney Cancer
• Kidney Neoplasms

Intervention

Drug:
• tinzaparin sodium

Locations

Country	Name	City	State
United States	Vermont Cancer Center at University of Vermont	Burlington	Vermont
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (2)

Lead Sponsor	Collaborator
University of Vermont	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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			No
Secondary	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			No
Secondary	Venous thromboembolism as measured by clinical evaluation at 6 months			No
Secondary	Progression free survival as measured by clinical evaluation at 4 months			No