Study of the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Effects of Vatalanib in Combination With Capecitabine in Patients With Advanced Cancer

Novartis

Status and phase

Completed

Phase 2

Phase 1

Conditions

Tumors

Neoplasm Metastasis

Treatments

Drug: PTK787/ZK 222584 (vatalanib)

Study type

Interventional

Funder types

Industry

Identifiers

NCT00171587

CPTK787 0134/306220

Details and patient eligibility

About

The objective of this study is to assess the safety, tolerability, dose limiting toxicity, and maximum tolerated dose of vatalanib administered orally once daily in combination with capecitabine in patients with advanced cancer. The study is also designed to determine the effect of vatalanib on the pharmacokinetics of capecitabine and the effect of capecitabine on the pharmacokinetics of vatalanib, and to describe the anti-tumor activity of this combination regimen.

Enrollment

22 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with histologically confirmed advanced cancer that is refractory to standard therapy or for which no standard therapy exists (for dose escalation phase of the study only)
Patients with histologically confirmed metastatic solid tumors or colorectal cancer presenting with metastatic disease and who received up to four prior chemotherapies for metastatic disease (for dose expansion phase of the study only)
Measurable or non-measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Age >= 18 years old
Karnofsky Performance Status (KPS) of >= 70
Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
Hemoglobin (Hgb) >= 9 g/dl
Platelets >= 100 x 10^9/L
Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) <= 3.0 x upper limit of normal (ULN)
Serum bilirubin <= 1.5 x ULN
Serum creatinine <= 1.5 x ULN and 24-hour creatinine clearance >= 50 ml/min
Total urinary protein in a 24-hour urine collection <= 500 mg
Life expectancy of greater than 3 months
Written informed consent obtained according to local guidelines

Exclusion criteria

Patients who have acute or chronic leukemias, lymphoma, or multiple myeloma
Patients who have known bone marrow involvement with tumor
Patients with a history of primary central nervous system tumors or brain metastases
Prior allogeneic, syngeneic, or autologous bone marrow transplant or stem cell transplant
Patients who have had more than two prior chemotherapy regimens for metastatic disease (for dose escalation phase of the study only)
Patients who have received chemotherapy less than 4 weeks (6 weeks for nitrosoureas or mitomycin-C and 2 weeks for vincristine) prior to entry on this study or who have not recovered from side effects of such therapy
Patients who have received immunotherapy within 2 weeks or who have not recovered from side effects of such therapy
Patients who have received radiotherapy within 2 weeks or who have not recovered from side effects of such therapy. The site of radiotherapy should not be the only site of measurable disease.
Major surgery within 2 weeks prior to entry on this study or patients who have not recovered from side effects of such therapy
Patients who have received investigational drugs within 4 weeks prior to entry on this study or who have not recovered from side effects of such therapy
Patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control. Oral, implantable, or injectable contraceptives are not considered an effective method of birth control for this study. (Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to administration of chemotherapy).
Concurrent severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, congestive cardiac failure, myocardial infarction within 6 months, poorly controlled hypertension, history of labile hypertension, history of poor compliance with antihypertensive regimen, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study
Acute or chronic liver disease (e.g., hepatitis, cirrhosis)
Confirmed diagnosis of HIV infection
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK787/ZK 222584 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the capsules/tablets)
Patients who are taking Coumadin (warfarin sodium)
Patients unwilling to or unable to comply with the protocol