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Phase I Study of the Oral Vascular Endothelial Growth Factor Inhibitor PTK787/ZK 222584 in Combination With Paclitaxel in Patients With Advanced Solid Tumors.


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Metastatic Non-hematologic Malignancies

Thank you

Trial Information

Phase I Study of the Oral Vascular Endothelial Growth Factor Inhibitor PTK787/ZK 222584 in Combination With Paclitaxel in Patients With Advanced Solid Tumors.


- 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.


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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety of PTK787/ZK 222584 in combination with paclitaxel

Outcome Time Frame:

2 years

Safety Issue:

Yes

Principal Investigator

Pankaj Bhargava, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

05-046

NCT ID:

NCT00358163

Start Date:

April 2006

Completion Date:

April 2010

Related Keywords:

  • Metastatic Non-hematologic Malignancies
  • angiogenesis
  • taxane
  • tyrosine kinase
  • pharmacokinetics
  • Vatalanib
  • Taxol
  • Neoplasms

Name

Location

Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Massachusetts General HospitalBoston, Massachusetts  02114-2617