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	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Drug: vatalanib  Drug: warfarin  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: anticoagulation  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy  Procedure: protein tyrosine kinase inhibitor therapy  Procedure: supportive care/therapy	Phase I

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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

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

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

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-7187,  United States; Recruiting

Study chairs or principal investigators

Joel Randolph Hecht, MD,  Principal Investigator,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000386239; UCLA-0403067-01; NOVARTIS-CPTK7870113; NCT00091299
Record last reviewed:  August 2004
Last Updated:  February 24, 2005
Record first received:  September 7, 2004
ClinicalTrials.gov Identifier:  NCT00091299
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08