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
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
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
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.
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])
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To evaluate acute and chronic changes in INR when Warfarin is co-administered with PTK787/ZK 222584
Outcome Time Frame:
2 weeks
Safety Issue:
No
Principal Investigator
Joel R. Hecht, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000386239
NCT ID:
NCT00091299
Start Date:
May 2004
Completion Date:
August 2012
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Jonsson Comprehensive Cancer Center at UCLA | Los Angeles, California 90095-1781 |
