Clinical trial NCT00784446: First-line Therapy of Stage IV Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Stage IV Colorectal Cancer
Keywords: AIO
colorectal cancer
0205
Capecitabine
Oxaliplatin
Bevacizumab
Imatinib
Lead sponsor: University of Cologne
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
name: Novartis
name: Sanofi
First posted: 2008-11-04
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Dose limiting toxicity.
timeFrame: 6 weeks
Secondary outcomes:
measure: Assessment of overall response rate and progression free survival.
timeFrame: 6 month
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: Medical Clinic for Haematology and Oncology
state: NRW
city: Esslingen
country: Germany
facility: Städische Kliniken Esslingen
city: Leipzig
country: Germany
facility: Klinikum St. Georg gGmbH
city: Mainz
country: Germany
facility: Johannes-Gutenberg-Universität Mainz
city: Mannheim
country: Germany
facility: Klinikum Mannheim
city: Recklinghausen
country: Germany
facility: Prosper-Hospital
city: Schweinfurt
country: Germany
facility: Leopoldina Krankenhaus
city: Ulm
country: Germany
facility: Universitätsklinik Ulm
Study officials:
affiliation: University Cologne
name: Ulrich Hacker, PD Dr.
role: PRINCIPAL_INVESTIGATOR
References: