Phase I, Pharmacokinetic, Pharmacodynamic Trial of PTK787 and Paclitaxel in Combination for Advanced Solid Tumors

Indiana University School of Medicine

Status and phase

Completed

Phase 1

Conditions

Carcinoma

Neoplasm Metastasis

Treatments

Drug: Paclitaxel plus PTK787

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00731861

0412-21/ IUCRO-0101

Details and patient eligibility

About

This study will evaluate PTK787, a new oral drug that stops blood vessel development, in combination with Paclitaxel in patients with advanced solid tumors.

Enrollment

28 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Adult patients with histologically confirmed malignancy that is unresponsive to curative therapy and for which no conventional therapy exists
ECOG Performance Status 0-2
Measurable or evaluable disease
Laboratory values within protocol limits within 2 weeks prior to registration
Life expectancy ≥ 12 weeks
Patient or guardian must have written informed consent obtained according to local guidelines
Women of child-bearing potential (non-sterile) must use appropriate barrier contraception for duration of study (negative pregnancy test required at baseline). Oral contraceptives will not be an acceptable form of contraception
Patients may have received prior standard taxane therapy, but have never progressed on taxane-based therapy.

Exclusion criteria

History or presence of central nervous system (CNS) disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis).
Prior chemotherapy ≤ 3 weeks prior to registration. Patients must have recovered from all therapy-related toxicities
Prior biologic or immunotherapy ≤ 2 weeks prior to registration. Patients must have recovered from all therapy-related toxicities
Prior full pelvic field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization.
Major surgery (i.e., laparotomy) ≤ 4 weeks prior to randomization. Minor surgery ≤ 2 weeks prior to randomization.
Patients who have received investigational drugs ≤ 4 weeks prior to registration
Prior therapy with anti-VEGF agents
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 not employing an effective method of birth control.
Patient agrees to avoid grapefruit (juice and fruit)

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
Congestive heart failure greater than NYHA classification ≥ Grade 1 (can be controlled with medication)
Myocardial infarction ≤ 6 months prior to registration and/or randomization
Serious uncontrolled cardiac arrhythmia
Uncontrolled diabetes at discretion of investigator
Active or uncontrolled infection requiring intravenous antibiotics
Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
Patients at risk of QT prolongation such as patients with congenital long QT syndrome or with long QTc at baseline (i.e. QTc greater than 450 msec in males, and greater than 470 msec in females) will be excluded