First-line Therapy of Stage IV Colorectal Cancer
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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 |
- Dose limiting toxicity. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
- 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:
|
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 |
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| 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 | |
| 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 May 19, 2013