First-line Therapy of Stage IV Colorectal Cancer

January 4, 2013 updated by: Ulrich Hacker, University of Cologne

A Phase I/II Study of Capecitabine/Oxaliplatin (XELOX) in Combination With Bevacizumab and Imatinib as First-line Treatment of Patients With Stage IV Colorectal Cancer

Assessment of safety and toxicity, definition of the dose limiting toxicity (DLT) of the combination therapy consisting of Capecitabine, Oxaliplatin, Bevacizumab and Imatinib.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The monoclonal anti-VEGF antibody bevacizumab has been approved for the treatment of stage IV colorectal cancer. The tyrosine kinase inhibitor imatinib mesylate has been shown to efficiently target PDGF-signalling. Blocking PDGFR-signalling leads to disruption of pericytes from the endothelium and reverses the maturation status thereby enhancing the sensitivity to anti-VEGF therapy.This background forms a rationale for a combined therapeutic PDGF and VEGF inhibition. Since bevacizumab shows best activity when used in combination with chemotherapy, capecitabine and oxaliplatin are included in this protocol. Patients with stage IV colorectal cancer and no prior chemotherapy can enter the study. Patients receive oral imatinib once a day on days 1-21. Oral Capecitabine is given on days 1-14 bid, Oxaliplatin and Bevacizumab are given on day 1. Courses are repeated every 22 days in the absence of disease progression or unacceptable toxicity.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Phase 2
  • Phase 1

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

  • Germany
      • Esslingen, Germany, 73730
        • Städische Kliniken Esslingen
      • Leipzig, Germany, 04129
        • Klinikum St. Georg gGmbH
      • Mainz, Germany, 55131
        • Johannes-Gutenberg-Universität Mainz
      • Mannheim, Germany, 68167
        • Klinikum Mannheim
      • Recklinghausen, Germany, 45659
        • Prosper-Hospital
      • Schweinfurt, Germany, 97422
        • Leopoldina Krankenhaus
      • Ulm, Germany, 89081
        • Universitätsklinik Ulm
    • NRW
      • Cologne, NRW, Germany, 50937
        • Medical Clinic for Haematology and Oncology

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:

  • Histologically proven inoperable colorectal cancer
  • Adult patients >= 18 years of age
  • ECOG <2

Exclusion Criteria:

  • Preceding chemo- or immunotherapy with the exception of adjuvant or neoadjuvant treatment of non-metastatic disease ending ≥ 6 month prior to study inclusion. Progression within 6 month after the end of adjuvant therapy must be excluded.
  • Other malignancies with the exception of basal cell carcinoma or successfully treated carcinoma in situ of the cervix uteri.
  • No history of severe comorbidities, i. e. uncontrolled hypertension, GI-bleeding, congestive heart-failure NYHA class II-IV, symptomatic coronary heart disease, myocardial infarction within 1 year prior to study inclusion, serious cardiac arrhythmias requiring medication, Grade II or greater peripheral vascular disease and other severe uncontrolled co-morbidities
  • No history of stroke or other CNS-diseases (tumors, seizure, transient ischemic attack etc.)
  • ≥ Grade II peripheral artery vascular occlusive disease
  • Preexisting neuropathy ≥ Grade 1
  • Interstitial pneumonia or lung fibrosis
  • Serious, nonhealing wound, ulcer, or bone fracture
  • Preceding irradiation an indicator lesion except for documented progressive disease during irradiation and termination of irradiation ≥ 4 weeks from study inclusion
  • Thromboembolic or bleeding events within the last 6 month
  • Need for therapeutic anticoagulation (heparin, cumarin)
  • Use of ASS > 325 mg/die or NSAR
  • Proteinuria > 1+ (stix) as long as urine protein >1g/24h

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
No Intervention: XELOX, Bevacizumab, Imatinib
Drug: Oxaliplatin, Capecitabine, Bevacizumab, Imatinib

Dose level I:

Bevacizumab day 1: 7,5 mg/kg body weight Oxaliplatin day 1: 100 mg/m2 Capecitabine days 1-14 bid: 800 mg/m2 Imatinib days 1-21: 300 mg

Repeat on day 22.

Dose level II:

Bevacizumab day 1: 7,5 mg/kg body weight Oxaliplatin day 1: 130 mg/m2 Capecitabine days 1-14 bid: 1000 mg/m2 Imatinib days 1-21: 300 mg

Repeat on day 22.

Other Names:
  • Avastin
  • Xeloda
  • Eloxatin
  • Imatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Dose limiting toxicity.
Time Frame: 6 weeks
6 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Assessment of overall response rate and progression free survival.
Time Frame: 6 month
6 month

Collaborators and Investigators

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

Sponsor

University of Cologne

Collaborators

Sanofi
Novartis
Roche Pharma AG

Investigators

  • Principal Investigator: Ulrich Hacker, PD Dr., University Cologne

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

April 1, 2008

Primary Completion (Actual)

August 1, 2010

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

November 3, 2008

First Submitted That Met QC Criteria

November 3, 2008

First Posted (Estimate)

November 4, 2008

Study Record Updates

Last Update Posted (Estimate)

January 7, 2013

Last Update Submitted That Met QC Criteria

January 4, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AIO KRK 0205
  • ML20344

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.

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