First-line Therapy of Stage IV Colorectal Cancer

Sponsor

University of Cologne (Other)

Overall Status

Completed

CT.gov ID

NCT00784446

Collaborator

Roche Pharma AG (Industry), Novartis (Industry), Sanofi (Industry)

Enrollment

Locations

Arm

Duration (Months)

6.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

51 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Apr 1, 2008

Actual Primary Completion Date :

Aug 1, 2010

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Dose limiting toxicity. [6 weeks]

Secondary Outcome Measures

Assessment of overall response rate and progression free survival. [6 month]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Medical Clinic for Haematology and Oncology	Cologne	NRW	Germany	50937
2	Städische Kliniken Esslingen	Esslingen		Germany	73730
3	Klinikum St. Georg gGmbH	Leipzig		Germany	04129
4	Johannes-Gutenberg-Universität Mainz	Mainz		Germany	55131
5	Klinikum Mannheim	Mannheim		Germany	68167
6	Prosper-Hospital	Recklinghausen		Germany	45659
7	Leopoldina Krankenhaus	Schweinfurt		Germany	97422
8	Universitätsklinik Ulm	Ulm		Germany	89081