Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Warfarin and Vatalanib in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI, Pharmaceutical / Industry UCLA-0403067-01 NOVARTIS-CPTK7870113, NCT00091299

Objectives

Primary

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

Secondary

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

Entry Criteria

Disease Characteristics:

• 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)
  • No poor metabolizers of CYP2C9 (2 allelles of either *2 or *3)



• No brain metastases

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• More than 14 days since prior anticancer chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• More than 14 days since prior anticancer hormonal therapy
• No concurrent hormonal therapy

Radiotherapy

• More than 14 days since prior anticancer radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• More than 14 days since other prior anticancer therapy
• More than 30 days since prior investigational drugs
• No other concurrent CYP2C9 substrates or inhibitors
• No concurrent CYP3A4 inducers or inhibitors
• No concurrent food or dietary supplement known to alter the metabolism of CYP3A4 (e.g., grapefruit or Hypericum perforatum [St. John's wort])
• No ethanol for 2 days prior to and for the first 17 days of study treatment

Patient Characteristics:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin ≥ 9 g/dL
• No history of or active coagulation disorders
• No significant risk for bleeding

Hepatic

• See Disease Characteristics
• 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

Renal

• Creatinine ≤ 1.5 ULN

  OR

• Creatinine clearance > 50 mL/min

Cardiovascular

• No uncontrolled high blood pressure (BP), defined as diastolic BP > 90 mm Hg or systolic BP > 140 mm Hg
• No history of cerebral or aortic aneurysm

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No recent history or evidence of drug or alcohol abuse
• No active peptic ulcer disease or gastrointestinal bleeding
• No contraindication or allergy to warfarin or related compounds
• No risk for adverse events related to prolonged PT/PTT due to warfarin administration
• No other medical condition that would preclude study participation

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Joel Hecht, MD, Principal investigator		Ph: 310-206-4303; 888-798-0719

Registry Information
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
Trial Start Date		2004-07-16
Registered in ClinicalTrials.gov		NCT00091299
Date Submitted to PDQ		2004-08-06
Information Last Verified		2005-12-29
NCI Grant/Contract Number		P30-CA16042