First-line Therapy of Stage IV Colorectal Cancer

NCT ID: NCT00784446

Last Updated: 2013-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2012-12-31

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.

Conditions

Stage IV Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

XELOX, Bevacizumab, Imatinib

Group Type: NO_INTERVENTION

Oxaliplatin, Capecitabine, Bevacizumab, Imatinib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Xeloda; Avastin; Imatinib; Eloxatin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

University of Cologne

OTHER

Sponsor Role: lead

Responsible Party

Ulrich Hacker

PD Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ulrich Hacker, PD Dr.

Role: PRINCIPAL_INVESTIGATOR

University Cologne

Locations

Medical Clinic for Haematology and Oncology

Cologne, North Rhine-Westphalia, Germany

Städische Kliniken Esslingen

Esslingen am Neckar, , 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, , Germany

Countries

Germany

Other Identifiers

ML20344

Identifier Type: -

Identifier Source: secondary_id

AIO KRK 0205

Identifier Type: -

Identifier Source: org_study_id