First-line Therapy of Stage IV Colorectal Cancer

This study has been completed.
Sponsor:
Collaborators:
Roche Pharma AG
Novartis
Sanofi
Information provided by (Responsible Party):
Ulrich Hacker, University of Cologne
ClinicalTrials.gov Identifier:
NCT00784446
First received: November 3, 2008
Last updated: January 4, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Stage IV Colorectal Cancer
Drug: Oxaliplatin, Capecitabine, Bevacizumab, Imatinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Cologne:

Primary Outcome Measures:
  • Dose limiting toxicity. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assessment of overall response rate and progression free survival. [ Time Frame: 6 month ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: April 2008
Study Completion Date: December 2012
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Xeloda
  • Avastin
  • Imatinib
  • Eloxatin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00784446

Locations
Germany
Medical Clinic for Haematology and Oncology
Cologne, NRW, Germany, 50937
Städische Kliniken Esslingen
Esslingen, Germany, 73730
Klinikum St. Georg gGmbH
Leipzig, Germany, 04129
Johannes-Gutenberg-Universität Mainz
Mainz, Germany, 55131
Klinikum Mannheim
Mannheim, Germany, 68167
Prosper-Hospital
Recklinghausen, Germany, 45659
Leopoldina Krankenhaus
Schweinfurt, Germany, 97422
Universitätsklinik Ulm
Ulm, Germany, 89081
Sponsors and Collaborators
University of Cologne
Roche Pharma AG
Novartis
Sanofi
Investigators
Principal Investigator: Ulrich Hacker, PD Dr. University Cologne
  More Information

No publications provided

Responsible Party: Ulrich Hacker, PD Dr., University of Cologne
ClinicalTrials.gov Identifier: NCT00784446     History of Changes
Other Study ID Numbers: AIO KRK 0205, ML20344
Study First Received: November 3, 2008
Last Updated: January 4, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Cologne:
AIO
colorectal cancer
0205
Capecitabine
Oxaliplatin
Bevacizumab
Imatinib

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Imatinib
Capecitabine
Bevacizumab
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances

ClinicalTrials.gov processed this record on July 23, 2014