PTK787/ZK222584 With Bevacizumab in Patients With Refractory and/or Advanced Malignancies

NCT00611793 | Completed Phase 1

• 1 other identifier: SCRI REFMAL 56
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

PTK787/ZK222584 is an orally active inhibitor of VEGF-R tyrosine kinases. Bevacizumab is an intravenous humanized monoclonal antibody directed against vascular endothelial growth factor. By binding to VEGF, bevacizumab blocks VEGF-A receptor binding. Due to the different mechanisms of action and the non-overlapping toxicity profiles of the two agents, it is hoped that a combination regimen incorporating both compounds will produce increased activity without enhanced toxicity.

Conditions

Refractory Malignancy; Advanced Malignancies

Keywords

Refractory Malignancy; Advanced Malignancies; PTK787/ZK222584; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  18 months

Study Arms (1)

1

EXPERIMENTAL

PTK787/ZK222584 and Bevacizumab

Drug: PTK787/ZK222584 and Bevacizumab

Interventions

PTK787/ZK222584 and Bevacizumab DRUG

PTK787/ZK222584 will be administered as a single agent orally on days 1-14 of cycle 1. The day 14 dose of PTK787/ZK222584 will be administered in the outpatient clinic and PK samples will be obtained. On Day 15 the patient will receive the initial dose of IV bevacizumab and PTK787/ZK222584. Bevacizumab will be repeated at 2 week intervals in patients with stable disease or better for four cycles of treatment (16 weeks). After four treatment cycles, only patients with a PR or CR will continue treatment with PTK787/ZK222584 and bevacizumab. Patients with stable disease may continue single agent PTK787/ZK22258 from cycle 5 onward. Protocol treatment will continue until disease progression or intolerable toxicity warrants drug discontinuation.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven advanced solid tumors that are resistant to standard treatment and/or for which there is no known effective therapy
• Age ≥ 18 years old
• ECOG Performance Status of 0 or 1
• Laboratory values ≤ 7 days prior to 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 ≤ 1.5 ULN
• International Normalized Ratio (INR) \<2.0
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3.0 x ULN
• 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
• Life expectancy ≥ 12 weeks
• Written informed consent obtained according to local guidelines

You may not qualify if:

• History or presence of central nervous system (CNS) disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis)
• Patients with a history of another primary malignancy ≤ 5 years, with the exception of inactive basal or squamous cell carcinoma of the skin
• Prior chemotherapy ≤ 3 weeks prior to registration and/or randomization. Patients must have recovered from all therapy-related toxicities
• Prior biologic or immunotherapy ≤ 2 weeks prior to registration and/or randomization. Patients must have recovered from all therapy-related toxicities
• Prior full field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization. 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 randomization. Minor surgery ≤ 2 weeks prior to randomization. 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 and/or randomization
• Prior therapy with anti-VEGF agents (including PTK787/ZK222584 and bevacizumab)
• 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. 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. Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to administration of study treatment. Please refer to appendix 3 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 (\>160/100 on medication), 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

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis: collaborator

Study Sites (1)

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

vatalanib; Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Howard A Burris, III, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 28, 2008
• First Posted: February 11, 2008
• Study Start: October 1, 2004
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2009
• Last Updated: January 23, 2009

Record last verified: 2009-01

Locations

US (1)