PTK787/ZK222584 in the Treatment of Metastatic Gastrointestinal Stromal Tumors Resistant to Imatinib

May 25, 2010 updated by: University of Helsinki

A Phase II, Open-Label Study of PTK787/ZK222584 in the Treatment of Metastatic Gastrointestinal Stromal Tumors (GISTs) Resistant to Imatinib Mesylate

This study evaluates the safety and efficacy of a novel tyrosine kinase inhibitor, PTK787/ZK222584, in the treatment of GIST (gastrointestinal stromal tumor) that is resistant to imatinib mesylate (Gleevec). The study participants are required to have histologically confirmed GIST with prior imatinib treatment for metastatic GIST. is administered orally 1250 mg/day. Six patients will first enter the study. If clinical benefit is obtained in >1 of 6 patients, 9 and 30 additional patients will be entered into the protocol in two stages (a maximum of 45 patients will be entered). Patients who benefit from the study treatment will be treated with PTK787/ZK222584 until treatment failure.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, phase II study of PTK787/ZK222584 designed to determine the safety and efficacy of PTK787/ZK222584 in the treatment of imatinib-resistant GIST. The PTK787/ZK222584 dose used is 1250 mg daily. Six patients will first enter the study using a two-stage approach. If clinical benefit is obtained in >1 of 6 patients, 9 and 30 additional patients will be entered into the protocol (a maximum total number of 45 patients will be entered). Clinical benefit is defined as the occurrence of one or more of the following 3 measures: 1) objective response to PTK787 (a confirmed or unconfirmed partial response [PR] or a complete response [CR]); 2) metabolic response defined as >50% decrease in the standardized uptake value (SUV) of FDG uptake in >1 FDG-avid lesions in one or more of the patients; or 3) stabilized disease for 3 months or longer accompanied by symptomatic or performance status improvement. Medical history, current medical conditions, weight, height, and an electrocardiogram are recorded prior to the study entry. Other baseline examinations include a chest X-ray, hematologic tests, a coagulation panel, serum chemistries, urine analysis, a serum pregnancy test and a radiological assessment of the tumor. Tumor response is monitored with imaging at 4- to 8-week intervals. Hematological tests and serum chemistries are evaluated at 1- to 4-week intervals, and adverse events are collected continuously. Research blood tests are collected at the times of tumor evaluations. Dose adjustments are carried out as per the protocol. Patients who benefit from the study treatment will be treated with PTK787/ZK222584 until treatment failure.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Finland
      • Helsinki, Finland, FIN-00029
        • Helsinki University Central Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with histologically confirmed GIST
  • Imatinib resistance (primary resistance with progression, or progression after initial response). Resistance is defined as objective evidence of progression after at least 4 weeks of treatment with imatinib.
  • Imatinib therapy has been interrupted >7 days before study entry
  • Metastatic disease confirmed histologically, cytologically or radiologically
  • Presence of measurable tumor lesions as determined by RECIST criteria
  • Age 18 years or older
  • WHO performance status of 2 or less
  • Blood neutrophil count (ANC) 1.5 x 10^9/L or higher
  • Platelet count 100 x 10^9/L or higher
  • Serum bilirubin 1.5 x ULN (upper limit of normal) or less
  • Serum creatinine 2.0 x ULN or less
  • Written informed consent obtained according to local guidelines

Exclusion Criteria:

  • Patients who have received chemotherapy less than 4 weeks prior to entry into this study or who have not recovered from side effects of such therapy
  • Patients who have received a cumulative dose of doxorubicin >450 mg/m2 or epirubicin 800 mg/m2
  • 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
  • Major surgery within 2 weeks prior to entry into 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 into 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
  • 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/ZK222584 (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); heparin is acceptable.
  • Patients unwilling to, or unable to, comply with the protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
PTK/ZK o.d. 1250 mg p.o.
Drug: PTK787/ZK222584
PTK787/ZK222584 is administered at the dosage of 1250 mg o.d. orally
Other Names:
  • vatalanib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Response rate
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Helsinki

Collaborators

Bayer

Investigators

  • Principal Investigator: Heikki Joensuu, M.D., Department of Oncology, Helsinki University Central Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2004

Primary Completion (Actual)

September 1, 2007

Study Completion (Actual)

January 1, 2009

Study Registration Dates

First Submitted

June 30, 2005

First Submitted That Met QC Criteria

June 30, 2005

First Posted (Estimate)

July 6, 2005

Study Record Updates

Last Update Posted (Estimate)

May 27, 2010

Last Update Submitted That Met QC Criteria

May 25, 2010

Last Verified

May 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CPTK787 A2401/300267
  • GIST PTK787/ZK222584

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sarcoma

Clinical Trials on PTK787/ZK222584

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Tunisia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe