Warfarin and Vatalanib in Treating Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00091299
First received: September 7, 2004
Last updated: August 2, 2012
Last verified: August 2012
  Purpose

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 Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: warfarin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • To evaluate acute and chronic changes in INR when Warfarin is co-administered with PTK787/ZK 222584 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the steady state pharmacokinetics of (R) and (S) Warfarin when co-administered with PTK787/ZK 222584 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Safety of low dose warfarin when co-administered with PTK787/ZK 222584 [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: May 2004
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: warfarin Drug: warfarin

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.

  Eligibility

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

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
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: NCT00091299

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-7187
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Joel R. Hecht, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00091299     History of Changes
Other Study ID Numbers: CDR0000386239, P30CA016042, UCLA-0403067-01, NOVARTIS-CPTK7870113
Study First Received: September 7, 2004
Last Updated: August 2, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Jonsson Comprehensive Cancer Center:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014