Trial of PTK787/ZK 222584 Plus Paclitaxel

Dana-Farber Cancer Institute

Status and phase

Terminated

Phase 1

Conditions

Metastatic Non-hematologic Malignancies

Treatments

Drug: paclitaxel

Drug: PTK787/ZK 222584

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00358163

05-046

Details and patient eligibility

About

PTK787/ZK 222584 is an inhibitor of VEGFR family tyrosine kinases. The primary objective of this study is to assess the safety of daily oral PTK787/ZK 222584 in combination with paclitaxel infused every 21 days. Secondary objectives include pharmacokinetic assessment of the impact of PTK787/ZK 222584 on paclitaxel metabolism and evaluation of tumor response to the investigational treatment.

Full description

We are looking for the highest dose of Paclitaxel that can be given safely in combination with the highest safe dose of Vatalanib. Therefore, not all people will receive the same dose of the study drug.
Small groups of people will be enrolled in steps on this trial. This first group will be given a certain dose of Paclitaxel and Vatalanib. If they have few or manageable side effects, the next small group of people enrolled will receive higher doses of the study drugs. This increase in doses will continue until the study doctors find the highest dose of the drugs that can be given without causing severe or unmanageable side effects.
In this study, Vatalanib tablets are taken daily, and paclitaxel is given by three-hour intravenous infusion once every 21 days.

Enrollment

7 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with advanced solid tumors for whom there is no potentially curative treatment (surgery, radiation therapy or chemotherapy).
Measurable or non-measurable disease
Age ≥ 18 years old
ECOG Performance Status 0 -1
Laboratory values ≤ 14 days weeks prior to starting study treatment:
Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L (≥ 1500/mm3)
Platelets (PLT) ≥ 100 x 109/L (≥ 100,000/mm3)
Hemoglobin (Hgb) ≥ 9 g/dL
Serum creatinine ≤ 1.5 ULN
Serum bilirubin ≤ 1.0 x ULN
Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 x ULN (≤ CTC grade 1).
Negative for proteinuria based on dip stick reading OR, if documentation of +1 result for protein on dip stick reading, then total urinary protein ≤ 500 mg and measured creatinine clearance (CrCl) ≥ 50 mL/min from a 24-hour urine collection
Women of child-bearing age must have a negative serum or urine test.
Life expectancy ≥ 12 weeks
Written informed consent obtained
Resolution of toxicity from previous chemotherapy to ≤ Grade I.
QTc interval ≤ 0.45 seconds (men) or ≤ 0.47 seconds (women).

Exclusion criteria

Previous hypersensitivity reaction to taxanes or cremophor.
History or presence of central nervous system (CNS) disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis).
Prior chemotherapy ≤ 4 weeks prior to registration. Prior nitrosoureas or mitomycin C ≤ 6 weeks prior to registration.
Prior biologic or immunotherapy ≤ 2 weeks prior to registration. Patients must have recovered from all therapy-related toxicities
Prior radiotherapy ≤ 4 weeks prior to registration. Patients must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease
Major surgery (i.e., laparotomy) ≤ 4 weeks prior to registration. Minor surgery ≤ 2 weeks prior to registration. Insertion of a vascular access device is not considered major or minor surgery in this regard. Patients must have recovered from all surgery-related toxicities
Patients who have received investigational drugs ≤ 4 weeks prior to registration.
Peripheral neuropathy with functional impairment ≥ CTC grade 2 neuropathy, regardless of causality.
Pleural effusion or ascites that causes respiratory compromise (≥ CTC grade 2 dyspnea)
Female patients who are pregnant or breast-feeding, or adults of reproductive potential who are not employing an effective method of birth control. Barrier contraceptives must be used throughout the trial in both sexes. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
Uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen
Unstable angina pectoris
Symptomatic congestive heart failure
Myocardial infarction ≤ 6 months prior to registration and/or randomization
Serious uncontrolled cardiac arrhythmia
Uncontrolled diabetes
Active or uncontrolled infection
Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
Acute or chronic liver disease (eg., hepatitis, cirrhosis)
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK787/ZK 222584 (i.e., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the tablets)
Patients with confirmed diagnosis of human immunodeficiency virus (HIV) infection are excluded at the investigator's discretion if he/she feels that 1) a potential drug interaction between PTK787/ZK 222584, paclitaxel and any of the patient's anti-HIV medications could influence the efficacy of the anti-HIV medication, or 2) it may place the patient at risk due to the pharmacologic activity of PTK787/ZK 222584. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
Patients who are taking therapeutic warfarin sodium (Coumadin) or similar oral anticoagulants that are metabolized by the cytochrome P450 system. Heparin products are allowed. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
Patients unwilling to or unable to comply with the protocol
Use of recombinant G-CSF products (Neupogen, Neulasta) within three weeks of registration. Chronic use of recombinant erythropoietin is permitted.