Know Cancer

or
forgot password

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


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

Thank you

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 UCLALos Angeles, California  90095-1781