Warfarin and Vatalanib in Treating Patients With Advanced Solid Tumors

Jonsson Comprehensive Cancer Center

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: warfarin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00091299

UCLA-0403067-01

CDR0000386239

NOVARTIS-CPTK7870113

Details and patient eligibility

About

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.

Full 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.

Enrollment

24 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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])