First-line Therapy of Stage IV Colorectal Cancer

Stage IV Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00784446
• Other study ID #: AIO KRK 0205
• Secondary ID: ML20344
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 3, 2008
• Last updated: January 4, 2013
• Start date: April 2008
• Est. completion date: December 2012

Study information

• Verified date: January 2013
• Source: University of Cologne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: December 2012
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Stage IV Colorectal Cancer

Intervention

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.

Locations

Country	Name	City	State
Germany	Medical Clinic for Haematology and Oncology	Cologne	NRW
Germany	Städische Kliniken Esslingen	Esslingen
Germany	Klinikum St. Georg gGmbH	Leipzig
Germany	Johannes-Gutenberg-Universität Mainz	Mainz
Germany	Klinikum Mannheim	Mannheim
Germany	Prosper-Hospital	Recklinghausen
Germany	Leopoldina Krankenhaus	Schweinfurt
Germany	Universitätsklinik Ulm	Ulm

Sponsors (4)

Lead Sponsor	Collaborator
University of Cologne	Novartis, Roche Pharma AG, Sanofi

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity.		6 weeks	Yes
Secondary	Assessment of overall response rate and progression free survival.		6 month	No