Warfarin and Vatalanib in Treating Patients With Advanced Solid Tumors

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00091299

Collaborator

Novartis Pharmaceuticals (Industry)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Vatalanib may stop the growth of tumor cells by stopping blood flow to the tumor. Warfarin may be effective in preventing the formation of blood clots in patients who are undergoing treatment for advanced solid tumors.

PURPOSE: This phase I trial is studying how well giving warfarin together with vatalanib works in treating patients with advanced solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: warfarin	Phase 1

Detailed Description

OBJECTIVES:

Primary

Determine the acute and chronic changes in INR in patients with advanced solid tumors treated with low-dose warfarin and vatalanib.

Secondary

Determine the steady-state pharmacokinetics of this regimen in these patients.
Determine the safety and tolerability of this regimen in these patients.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

Pharmacokinetic (PK) phase: Patients receive oral low-dose warfarin once daily on days 1-14 and oral vatalanib once daily, 1 hour before warfarin administration, on days 2-14 in the absence of disease progression or unacceptable toxicity.
Continuation phase: Patients not experiencing a drug interaction in the PK phase continue to receive oral vatalanib and oral low-dose warfarin once daily. Patients experiencing a drug interaction (INR > 2.0) in the PK phase receive oral vatalanib alone once daily. Continuation therapy continues indefinitely in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open Label, Non Randomized , One Sequence, Add-On Study to Investigate the Effects of PTK787/ZK 222584 on the Pharmacokinetics and Pharmacodynamics of Warfarin at Steady-States in Cancer Patients

Study Start Date :

May 1, 2004

Actual Primary Completion Date :

Aug 1, 2012

Actual Study Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: warfarin	Drug: warfarin

Arm

Intervention/Treatment

Experimental: warfarin

Drug: warfarin

Outcome Measures

Primary Outcome Measures

To evaluate acute and chronic changes in INR when Warfarin is co-administered with PTK787/ZK 222584 [2 weeks]

Secondary Outcome Measures

To evaluate the steady state pharmacokinetics of (R) and (S) Warfarin when co-administered with PTK787/ZK 222584 [2 weeks]
Safety of low dose warfarin when co-administered with PTK787/ZK 222584 [2 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed advanced solid tumor
Progressed despite standard therapy OR no known standard therapy exists

-- Currently receiving OR a candidate for prophylactic low-dose warfarin (1 mg/day)

INR ≤ 1.4
Must be an extensive metabolizer of CYP2C9 (at least 1 wild type allelle: *1)
18 and over
Hemoglobin ≥ 9 g/dL
AST and ALT ≤ 3 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
Albumin ≥ 3.0 g/dL
Hepatitis B surface antigen negative
Hepatitis C antibody negative
Creatinine ≤ 1.5 ULN OR
Creatinine clearance > 50 mL/min
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
More than 14 days since prior anticancer chemotherapy
More than 14 days since prior anticancer hormonal therapy
More than 14 days since prior anticancer radiotherapy
More than 14 days since other prior anticancer therapy
More than 30 days since prior investigational drugs
No ethanol for 2 days prior to and for the first 17 days of study treatment

Exclusion Criteria:

No poor metabolizers of CYP2C9 (2 alleles of either *2 or *3)
brain metastases
history of or active coagulation disorders
significant risk for bleeding
uncontrolled high blood pressure (BP), defined as diastolic BP > 90 mm Hg or systolic BP > 140 mm Hg
history of cerebral or aortic aneurysm
pregnant or nursing
recent history or evidence of drug or alcohol abuse
active peptic ulcer disease or gastrointestinal bleeding
contraindication or allergy to warfarin or related compounds
risk for adverse events related to prolonged PT/PTT due to warfarin administration
other medical condition that would preclude study participation
concurrent chemotherapy
concurrent hormonal therapy
concurrent radiotherapy
other concurrent CYP2C9 substrates or inhibitors
concurrent CYP3A4 inducers or inhibitors
concurrent food or dietary supplement known to alter the metabolism of CYP3A4 (e.g., grapefruit or Hypericum perforatum [St. John's wort])

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-7187

Sponsors and Collaborators

Jonsson Comprehensive Cancer Center
Novartis Pharmaceuticals

Investigators

Principal Investigator: Joel R. Hecht, MD, Jonsson Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jonsson Comprehensive Cancer Center

ClinicalTrials.gov Identifier:

NCT00091299

Other Study ID Numbers:

CDR0000386239
UCLA-0403067-01
NOVARTIS-CPTK7870113

First Posted:

Sep 9, 2004

Last Update Posted:

Aug 5, 2020

Last Verified:

Aug 1, 2012

Keywords provided by Jonsson Comprehensive Cancer Center

unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Warfarin

Study Results

No Results Posted as of Aug 5, 2020