Stage IV Colorectal Cancer
Conditions
Keywords
AIO, colorectal cancer, 0205, Capecitabine, Oxaliplatin, Bevacizumab, Imatinib
Brief summary
Assessment of safety and toxicity, definition of the dose limiting toxicity (DLT) of the combination therapy consisting of Capecitabine, Oxaliplatin, Bevacizumab and Imatinib.
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.
Interventions
DRUGOxaliplatin, 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.
Sponsors
Roche Pharma AG
Novartis
Sanofi
University of Cologne
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity. | 6 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Assessment of overall response rate and progression free survival. | 6 month |
Countries
Germany
Outcome results
None listed